Pharmacodynamics of Isavuconazole in a Dynamic In Vitro Model of Invasive Pulmonary Aspergillosis

PubMed Central

Box, Helen; Livermore, Joanne; Johnson, Adam; McEntee, Laura; Felton, Timothy W.; Whalley, Sarah; Goodwin, Joanne

2015-01-01

Isavuconazonium sulfate is a novel triazole prodrug that has been recently approved for the treatment of invasive aspergillosis by the FDA. The active moiety (isavuconazole) has a broad spectrum of activity against many pathogenic fungi. This study utilized a dynamic in vitro model of the human alveolus to describe the pharmacodynamics of isavuconazole against two wild-type and two previously defined azole-resistant isolates of Aspergillus fumigatus. A human-like concentration-time profile for isavuconazole was generated. MICs were determined using CLSI and EUCAST methodologies. Galactomannan was used as a measure of fungal burden. Target values for the area under the concentration-time curve (AUC)/MIC were calculated using a population pharmacokinetics-pharmacodynamics (PK-PD) mathematical model. Isolates with higher MICs required higher AUCs in order to achieve maximal suppression of galactomannan. The AUC/MIC targets necessary to achieve 90% probability of galactomannan suppression of <1 were 11.40 and 11.20 for EUCAST and CLSI, respectively. PMID:26503648

Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium-intracellulare complex.

PubMed

Maurer, Florian P; Pohle, Philipp; Kernbach, Margrit; Sievert, Daniela; Hillemann, Doris; Rupp, Jan; Hombach, Michael; Kranzer, Katharina

2018-06-12

To determine MIC distributions for Mycobacterium chimaera, Mycobacterium intracellulare, Mycobacterium colombiense and Mycobacterium avium, and to derive tentative epidemiological cutoff (ECOFF) values. 683 bacterial isolates (M. chimaera, n = 203; M. intracellulare; n = 77; M. colombiense, n = 68; M. avium, n = 335) from 627 patients were tested by broth microdilution according to CLSI protocol M24-A2 on Sensititre RAPMYCOI plates. MICs were interpreted based on CLSI breakpoints for clarithromycin, and tentative breakpoints for amikacin, moxifloxacin and linezolid. Tentative ECOFFs were determined by visual approximation and the ECOFFinder algorithm. Modal MIC, MIC 50 and MIC 90 values were within ± one dilution step from the respective aggregated dataset for 47 / 48 (97.9 %), 48 / 48 (100 %), and 48 / 48 (100 %) species-drug combinations. Clarithromycin wild-type populations were mostly classified as susceptible (MIC 90 = 4 to 8 mg / l; S ≤ 8 mg/l). Rifabutin MICs were lower than those of rifampicin. Tentative moxifloxacin, linezolid and amikacin breakpoints split wild-type populations. No ECOFFs could be set for rifampicin, ethambutol, ciprofloxacin, isoniazid, trimethoprim/sulfamethoxazole and doxycycline due to truncation of MIC distributions. Agreement between the visually determined and the modelled 97.5 % ECOFFs was 90.9 %. All 99.0 % ECOFFs were one titer step higher than by visual approximation. Drug susceptibility patterns of M. chimaera are comparable to those of closely related species. Except for clarithromycin, breakpoints for MAIC should be reevaluated. Statistical determination of the 99.0 % ECOFF may be superior to visual approximation. Copyright © 2018. Published by Elsevier Ltd.

[Determination of sensitivity of biofilm-positive forms of microorganisms to antibiotics].

PubMed

Holá, Veronika; Růzicka, Filip; Tejkalová, Renata; Votava, Miroslav

2004-10-01

Nosocomial infections caused by biofilm-positive microorganisms are a serious therapeutic problem. In the biofilm, microorganisms are protected against adverse effects of the external environment, including the action of antibiotics. It is well known that the values of minimum inhibitory concentrations (MIC) determined for planktonic forms do not correspond to the actual concentrations of antibiotics necessary for the eradication of bacteria in a biofilm. The purpose of the study was to propose a method of determining minimum biofilm inhibitory concentrations (MBIC) and minimum biofilm eradication concentrations (MBEC) and to compare these values with MIC values. Biofilm-positive strains of Staphylococcus epidermidis were cultured so as to form a biofilm layer on polystyrene pegs. The biofilm on the pegs was then exposed to the action of antibiotics and after 18 hours we determined the minimum biofilm inhibitory concentration (MBIC). The evaluation of minimum biofilm eradication concentrations was done colorimetrically from the metabolic activity of surviving cells. MBIC and MBEC values were many times higher than MIC values. We selected such a duration of the biofilms cultivation on the pegs of the plate, which ensured that the number of bacterial cells corresponded to standard MIC assessment. The MBEC values established in our study indicate that the currently used concentrations of tested antibiotics cannot be used in monotherapy for an efficacious eradication of a biofilm. The MBEC determination is a far more laborious and time-consuming method than the determination of MIC, but the use of plates with pegs facilitates the handling of biofilms. The advantage of our method is the possibility of standardization of the size of the inoculum and thus of the whole MBEC assessment.

Comparison of Spectrophotometric and Visual Readings of NCCLS Method and Evaluation of a Colorimetric Method Based on Reduction of a Soluble Tetrazolium Salt, 2,3-Bis {2-Methoxy-4-Nitro-5-[(Sulfenylamino) Carbonyl]-2H- Tetrazolium-Hydroxide}, for Antifungal Susceptibility Testing of Aspergillus Species

PubMed Central

Meletiadis, Joseph; Mouton, Johan W.; Meis, Jacques F. G. M.; Bouman, Bianca A.; Donnelly, Peter J.; Verweij, Paul E.

2001-01-01

The susceptibilities of 25 clinical isolates of various Aspergillus species (Aspergillus fumigatus, A. flavus, A. terreus, A. ustus, and A. nidulans) to itraconazole (ITC) and amphotericin B (AMB) were determined using the standard proposed by NCCLS for antifungal susceptibility testing of filamentous fungi, a modification of this method using spectrophotometric readings, and a colorimetric method using the tetrazolium salt 2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium-hydroxide} (XTT). Five MIC end points for ITC (MIC-0, no visible growth or ≤5% the growth control value [GC]; MIC-1, slight growth or 6 to 25% the GC; MIC-2, prominent reduction in growth or 26 to 50% the GC; MIC-3, slight reduction in growth or 51 to 75% the GC; and MIC-4, no reduction in growth or 76 to 100% the GC) and one for AMB (MIC-0) were determined visually by four observers and spectrophotometrically. The intraexperimental (between the observers) and interexperimental (between the experiments) levels of agreement of the NCCLS and XTT methods exceeded 95% for MIC-0 of AMB and MIC-0 and MIC-1 of ITC. The MIC-2 of ITC showed lower reproducibility, although spectrophotometric reading and/or incubation for 48 h increased the interexperimental reproducibility from 85 to >93%. Between visual and spectrophotometric readings, high levels of agreement were found for AMB (≈97%) and MIC-1 (≈92%) and MIC-2 (≈88%) of ITC. Poor agreement was found for MIC-0 of ITC (51% after 24 h), since the spectrophotometric readings resulted in higher MIC-0 values than the visual readings. The agreement was increased to 98% by shifting the threshold level of MIC-0 from 5 to 10% relative optical density and by establishing an optical density of greater than 0.1 for the GC as the validation criterion. No statistically significant differences were found between the NCCLS method and the XTT method, with the levels of agreement exceeding 97% for MIC-0 of AMB and 83% for MIC-0, MIC-1, and MIC-2 of ITC. The XTT method and spectrophotometric readings can increase the sensitivity and the precision, respectively, of in vitro susceptibility testing of Aspergillus species. PMID:11724829

In vitro assessment of the antimicrobial susceptibility of caprine isolates of Mycoplasma mycoides subsp. capri.

PubMed

Paterna, A; Tatay-Dualde, J; Amores, J; Prats-van der Ham, M; Sánchez, A; de la Fe, C; Contreras, A; Corrales, J C; Gómez-Martín, Á

2016-08-01

The minimum inhibitory concentration (MIC) and minimum mycoplasmacidal concentration (MMC) of 17 antimicrobials against 41 Spanish caprine isolates of Mycoplasma mycoides subsp. capri (Mmc) obtained from different specimens (milk, external auricular canal and semen) were determined using a liquid microdilution method. For half of the isolates, the MIC was also estimated for seven of the antimicrobials using an epsilometric test (ET), in order to compare both methods and assess the validity of ET. Mutations in genes gyrA, gyrB, parC and parE conferring fluoroquinolone resistance, which have been recently described in Mmc, were investigated using PCR. The anatomical origin of the isolate had no effect on its antimicrobial susceptibility. Moxifloxacin and doxycycline had the lowest MIC values. The rest of the fluoroquinolones studied (except norfloxacin), together with tylosin and clindamycin, also had low MIC values, although the MMC obtained for clindamycin was higher than for the other antimicrobials. For all the aminoglycosides, spiramycin and erythromycin, a notable level of resistance was observed. The ET was in close agreement with broth microdilution at low MICs, but not at intermediate or high MICs. The analysis of the genomic sequences revealed the presence of an amino acid substitution in codon 83 of the gene gyrA, which has not been described previously in Mmc. Copyright © 2016 Elsevier Ltd. All rights reserved.

High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus

PubMed Central

Viedma, Esther; Chaves, Fernando; Lalueza, Antonio; Fortún, Jesús; Loza, Elena; Pujol, Miquel; Ardanuy, Carmen; Morales, Isabel; de Cueto, Marina; Resino-Foz, Elena; Morales-Cartagena, Alejandra; Rico, Alicia; Romero, María P.; Orellana, María Ángeles; López-Medrano, Francisco; Fernández-Ruiz, Mario; Aguado, José María

2016-01-01

We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011–June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2–5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1–5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. PMID:27192097

Short communication: In vitro antimicrobial susceptibility of Mycoplasma agalactiae strains isolated from dairy goats.

PubMed

Paterna, A; Sánchez, A; Gómez-Martín, A; Corrales, J C; De la Fe, C; Contreras, A; Amores, J

2013-01-01

This study examined the susceptibility to several antimicrobials of 28 isolates of Mycoplasma agalactiae obtained from goats in a region (southeastern Spain) where contagious agalactia is endemic. For each isolate, the minimum inhibitory concentration (MIC) against 12 antimicrobials of the quinolone, macrolide, aminoglycoside, and tetracycline families was determined. The antimicrobials with the lowest MIC were enrofloxacin, ciprofloxacin, tylosin, and doxycycline, all with MIC90 (concentration at which growth of 90% of the isolates is inhibited) <1 µg/mL. Norfloxacin (a quinolone) showed a wide MIC range (0.1-12.8 µg/mL), suggesting a resistance mechanism toward this antimicrobial that was not elicited by enrofloxacin or ciprofloxacin (the other quinolones tested). Erythromycin showed the highest MIC90 such that its use against Mycoplasma agalactiae is not recommended. Finally, Mycoplasma agalactiae isolates obtained from goat herds with clinical symptoms of contagious agalactia featured higher MIC90 and MIC50 (concentration at which growth of 50% of the isolates is inhibited) values for many of the antimicrobials compared with isolates from asymptomatic animals. The relationship between the extensive use of antimicrobials in herds with clinical contagious agalactia and variations in MIC requires further study. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparative Study of Betacyanin Profile and Antimicrobial Activity of Red Pitahaya (Hylocereus polyrhizus) and Red Spinach (Amaranthus dubius).

PubMed

Yong, Yi Yi; Dykes, Gary; Lee, Sui Mae; Choo, Wee Sim

2017-03-01

Betacyanins are reddish to violet pigments that can be found in red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius). This study investigated the impact of sub-fractionation (solvent partitioning) on betacyanin content in both plants. Characterization of betacyanins and evaluation of their antimicrobial activities were also carried out. Betanin was found in both plants. In addition, isobetanin, phyllocactin and hylocerenin were found in red pitahaya whereas amaranthine and decarboxy-amaranthine were found in red spinach. Sub-fractionated red pitahaya and red spinach had 23.5 and 121.5 % more betacyanin content, respectively, than those without sub-fractionation. Sub-fractionation increased the betanin and decarboxy-amaranthine content in red pitahaya and red spinach, respectively. The betacyanin fraction from red spinach (minimum inhibitory concentration [MIC] values: 0.78-3.13 mg/mL) demonstrated a better antimicrobial activity profile than that of red pitahaya (MIC values: 3.13-6.25 mg/mL) against nine Gram-positive bacterial strains. Similarly, the red spinach fraction (MIC values: 1.56-3.13 mg/mL) was more active than the red pitahaya fraction (MIC values: 3.13-6.25 mg/mL) against five Gram-negative bacterial strains. This could be because of a higher amount of betacyanin, particularly amaranthine in the red spinach.

Antibacterial activity of Zuccagnia punctata Cav. ethanolic extracts.

PubMed

Zampini, Iris C; Vattuone, Marta A; Isla, Maria I

2005-12-01

The present study was conducted to investigate antibacterial activity of Zuccagnia punctata ethanolic extract against 47 strains of antibiotic-resistant Gram-negative bacteria and to identify bioactive compounds. Inhibition of bacterial growth was investigated using agar diffusion, agar macrodilution, broth microdilution and bioautographic methods. Zuccagnia punctata extract was active against all assayed bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia) with minimal inhibitory concentration (MIC) values ranging from 25 to 200 microg/mL. Minimal bactericidal concentration (MBC) values were identical or two-fold higher than the corresponding MIC values. Contact bioautography, indicated that Zuccagnia punctata extracts possess one major antibacterial component against Pseudomonas aeruginosa and at least three components against. Klebsiella pneumoniae and Escherichia coli. Activity-guided fractionation of 1he ethanol extract on a silica gel column yielded a compound (2',4'-dihydroxychalcone), which exhibited strong antibacterial activity with MIC values between 0.10 and 1.00 microg/mL for Proteus mirabilis, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia. These values are lower than imipenem (0.25-16 microg/mL). Zuccagnia punctata might provide promising therapeutic agents against infections with multi-resistant Gram-negative bacteria.

Pharmacodynamic effects of amoxicillin versus cefotaxime against penicillin-susceptible and penicillin-resistant pneumococcal strains: a phase I study.

PubMed Central

Aguilar, L; Rosendo, J; Balcabao, I P; Martín, M; Giménez, M J; Frías, J; Prieto, J

1997-01-01

Serum bactericidal activity against a penicillin-susceptible strain and a penicillin-resistant strain of Streptococcus pneumoniae (amoxicillin and cefotaxime MICs, 0.001 and 1 microg/ml, respectively, and MBCs, 0.01 and 2 microg/ml, respectively) was measured in 12 healthy volunteers who each received an oral 875-mg dose of amoxicillin and an intramuscular 1-g dose of cefotaxime in a crossover fashion. The areas under the bactericidal activity-time curves for the two strains were found to be similar for both antibiotics despite the significantly higher (P < 0.002) AUC/MIC and peak level/MIC values for cefotaxime. PMID:9174206

[Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method].

PubMed

Matsuo, K; Uete, T

1992-10-01

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)

In vitro activity of the novel echinocandin CD101 at pH 7 and 4 against Candida spp. isolates from patients with vulvovaginal candidiasis

PubMed Central

Boikov, Dina A.; James, Kenneth D.; Bartizal, Ken; Sobel, Jack D.

2017-01-01

Background: The novel echinocandin CD101 has stability properties amenable to topical formulation for use in the treatment of acute vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). CD101 has demonstrated potent antifungal activity at pH 7, but assessment of its activity at the physiological pH of the vaginal environment is needed. Objectives: To evaluate the antifungal activity of CD101 against clinical VVC isolates of Candida spp., including azole-resistant strains, at pH 4. Methods: MIC values of CD101 and comparators (fluconazole, itraconazole, micafungin, caspofungin and anidulafungin) were assessed via broth microdilution. MIC assays were conducted at pH 7 and 4 after 24 and 48 h against a 108 VVC isolate panel of Candida spp., including Candida albicans (n = 60), Candida glabrata (n = 21), Candida parapsilosis (n = 14) and Candida tropicalis (n = 13). Results: Overall, MIC values of all drugs were slightly higher at pH 4 versus 7 and at 48 versus 24 h of incubation. CD101 MIC values typically exhibited ∼4-fold shifts at pH 4 and were not affected by azole susceptibility. C. parapsilosis susceptibility was the least affected at pH 4 and did not increase for most drugs. Conclusions: CD101 had potent activity against all Candida isolates tested, including azole-resistant strains. Although there was some reduction in activity at pH 4 versus 7, the resulting MIC values were still well below the intravaginal CD101 drug concentrations anticipated to be present following topical administration. These results support continued development of topical CD101 for the treatment of VVC/RVVC. PMID:28158577

In vitro activity of the novel echinocandin CD101 at pH 7 and 4 against Candida spp. isolates from patients with vulvovaginal candidiasis.

PubMed

Boikov, Dina A; Locke, Jeffrey B; James, Kenneth D; Bartizal, Ken; Sobel, Jack D

2017-05-01

The novel echinocandin CD101 has stability properties amenable to topical formulation for use in the treatment of acute vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). CD101 has demonstrated potent antifungal activity at pH 7, but assessment of its activity at the physiological pH of the vaginal environment is needed. To evaluate the antifungal activity of CD101 against clinical VVC isolates of Candida spp., including azole-resistant strains, at pH 4. MIC values of CD101 and comparators (fluconazole, itraconazole, micafungin, caspofungin and anidulafungin) were assessed via broth microdilution. MIC assays were conducted at pH 7 and 4 after 24 and 48 h against a 108 VVC isolate panel of Candida spp., including Candida albicans ( n  =   60), Candida glabrata ( n  =   21), Candida parapsilosis ( n  =   14) and Candida tropicalis ( n  =   13). Overall, MIC values of all drugs were slightly higher at pH 4 versus 7 and at 48 versus 24 h of incubation. CD101 MIC values typically exhibited ∼4-fold shifts at pH 4 and were not affected by azole susceptibility. C. parapsilosis susceptibility was the least affected at pH 4 and did not increase for most drugs. CD101 had potent activity against all Candida isolates tested, including azole-resistant strains. Although there was some reduction in activity at pH 4 versus 7, the resulting MIC values were still well below the intravaginal CD101 drug concentrations anticipated to be present following topical administration. These results support continued development of topical CD101 for the treatment of VVC/RVVC. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Evaluation of the efficacy of four weak acids as antifungal preservatives in low-acid intermediate moisture model food systems.

PubMed

Huang, Yang; Wilson, Mark; Chapman, Belinda; Hocking, Ailsa D

2010-02-01

The potential efficacy of four weak acids as preservatives in low-acid intermediate moisture foods was assessed using a glycerol based agar medium. The minimum inhibitory concentrations (MIC, % wt./wt.) of each acid was determined at two pH values (pH 5.0, pH 6.0) and two a(w) values (0.85, 0.90) for five food spoilage fungi, Eurotium herbariorum, Eurotium rubrum, Aspergillus niger, Aspergillus flavus and Penicillium roqueforti. Sorbic acid, a preservative commonly used to control fungal growth in low-acid intermediate moisture foods, was included as a reference. The MIC values of the four acids were lower at pH 5.0 than pH 6.0 at equivalent a(w) values, and lower at 0.85 a(w) than 0.90 a(w) at equivalent pH values. By comparison with the MIC values of sorbic acid, those of caprylic acid and dehydroacetic acid were generally lower, whereas those for caproic acid were generally higher. No general observation could be made in the case of capric acid. The antifungal activities of all five weak acids appeared related not only to the undissociated form, but also the dissociated form, of each acid.

Activities of a new oral streptogramin, XRP 2868, compared to those of other agents against Streptococcus pneumoniae and haemophilus species.

PubMed

Pankuch, Glenn A; Kelly, Linda M; Lin, Gengrong; Bryskier, Andre; Couturier, Catherine; Jacobs, Michael R; Appelbaum, Peter C

2003-10-01

MIC methodology was used to test the antibacterial activity of XRP 2868, a new oral combination of two semisynthetic streptogramins, RPR 132552A and RPR 202868, compared to activities of other antibacterial agents against pneumococci, Haemophilus influenzae, and Haemophilus parainfluenzae. For 261 pneumococci, XRP 2868 and pristinamycin MICs were similar, irrespective of penicillin G and erythromycin A susceptibilities (MIC at which 50% of isolates were inhibited [MIC(50)], 0.25 micro g/ml; MIC(90), 0.5 micro g/ml), while quinupristin/dalfopristin had MICs which were 1 to 2 dilutions higher. Single components of both XRP 2868 and quinupristin/dalfopristin had higher MICs. Erythromycin A, azithromycin, clarithromycin, and clindamycin MICs were higher for penicillin G-intermediate and -resistant than -susceptible pneumococci. Against 150 H. influenzae strains, all compounds tested had unimodal MIC distributions. XRP 2868 had an overall MIC(50) of 0.25 micro g/ml and an MIC(90) of 1.0 micro g/ml, with no differences between beta-lactamase-positive, beta-lactamase-negative, and beta-lactamase-negative ampicillin-resistant strains. Of note was the similarly low activity of one of its components, RPR 132552A. Pristinamycin and quinupristin/dalfopristin had MICs of 0.125 to 8.0 micro g/ml; quinupristin alone had MICs of 8.0 to >64.0 micro g/ml, and dalfopristin had MICs of 1.0 to >64.0 micro g/ml. Erythromycin A, azithromycin, and clarithromycin had modal MICs of 4.0, 1.0, and 8.0 micro g/ml, respectively. MICs of all compounds against H. parainfluenzae were 1 to 2 dilutions higher than against H. influenzae. XRP 2868 showed potent activity against pneumococci and Haemophilus strains irrespective of their susceptibility to other agents.

Activities of a New Oral Streptogramin, XRP 2868, Compared to Those of Other Agents against Streptococcus pneumoniae and Haemophilus Species

PubMed Central

Pankuch, Glenn A.; Kelly, Linda M.; Lin, Gengrong; Bryskier, Andre; Couturier, Catherine; Jacobs, Michael R.; Appelbaum, Peter C.

2003-01-01

MIC methodology was used to test the antibacterial activity of XRP 2868, a new oral combination of two semisynthetic streptogramins, RPR 132552A and RPR 202868, compared to activities of other antibacterial agents against pneumococci, Haemophilus influenzae, and Haemophilus parainfluenzae. For 261 pneumococci, XRP 2868 and pristinamycin MICs were similar, irrespective of penicillin G and erythromycin A susceptibilities (MIC at which 50% of isolates were inhibited [MIC50], 0.25 μg/ml; MIC90, 0.5 μg/ml), while quinupristin/dalfopristin had MICs which were 1 to 2 dilutions higher. Single components of both XRP 2868 and quinupristin/dalfopristin had higher MICs. Erythromycin A, azithromycin, clarithromycin, and clindamycin MICs were higher for penicillin G-intermediate and -resistant than -susceptible pneumococci. Against 150 H. influenzae strains, all compounds tested had unimodal MIC distributions. XRP 2868 had an overall MIC50 of 0.25 μg/ml and an MIC90 of 1.0 μg/ml, with no differences between β-lactamase-positive, β-lactamase-negative, and β-lactamase-negative ampicillin-resistant strains. Of note was the similarly low activity of one of its components, RPR 132552A. Pristinamycin and quinupristin/dalfopristin had MICs of 0.125 to 8.0 μg/ml; quinupristin alone had MICs of 8.0 to >64.0 μg/ml, and dalfopristin had MICs of 1.0 to >64.0 μg/ml. Erythromycin A, azithromycin, and clarithromycin had modal MICs of 4.0, 1.0, and 8.0 μg/ml, respectively. MICs of all compounds against H. parainfluenzae were 1 to 2 dilutions higher than against H. influenzae. XRP 2868 showed potent activity against pneumococci and Haemophilus strains irrespective of their susceptibility to other agents. PMID:14506040

Comparative Pharmacodynamics and Antimutant Potentials of Doripenem and Imipenem with Ciprofloxacin-Resistant Pseudomonas aeruginosa in an In Vitro Model

PubMed Central

Gilbert, Deborah; Greer, Kenneth; Portnoy, Yury A.; Zinner, Stephen H.

2012-01-01

To compare the antipseudomonal efficacy of doripenem and imipenem as well as their abilities to restrict the enrichment of resistant Pseudomonas aeruginosa, multiple-dosing regimens of each drug were simulated at comparable values of the cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (T>MIC) and ratios of the 24-hour area under the curve (AUC24) to the MIC. Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem, 1 μg/ml; MICs of imipenem, 1, 2, and 2 μg/ml) were exposed to thrice-daily doripenem or imipenem for 3 days at AUC24/MIC ratios of from 50 to 170 h (doripenem) and from 30 to 140 h (imipenem). The antimicrobial effects for susceptible and resistant subpopulations of bacteria were expressed by the areas between control growth and time-kill curves (IEs) and areas under the bacterial mutant concentration curves (AUBCMs), respectively. With each antibiotic, the IE and AUBCM versus log AUC24/MIC relationships were bacterial strain independent. At similar AUC24/MIC ratios, doripenem was slightly less efficient than imipenem against susceptible and resistant subpopulations of bacteria. However, doripenem appeared to be somewhat more efficient than imipenem at clinically achievable AUC24s related to the means of the MICs for the three studied strains and had higher antimutant potentials for two of the three strains. PMID:22203591

Susceptibility screening of hyphae-forming fungi with a new, easy, and fast inoculum preparation method.

PubMed

Schmalreck, Arno; Willinger, Birgit; Czaika, Viktor; Fegeler, Wolfgang; Becker, Karsten; Blum, Gerhard; Lass-Flörl, Cornelia

2012-12-01

In vitro susceptibility testing of clinically important fungi becomes more and more essential due to the rising number of fungal infections in patients with impaired immune system. Existing standardized microbroth dilution methods for in vitro testing of molds (CLSI, EUCAST) are not intended for routine testing. These methods are very time-consuming and dependent on sporulating of hyphomycetes. In this multicentre study, a new (independent of sporulation) inoculum preparation method (containing a mixture of vegetative cells, hyphae, and conidia) was evaluated. Minimal inhibitory concentrations (MIC) of amphotericin B, posaconazole, and voriconazole of 180 molds were determined with two different culture media (YST and RPMI 1640) according to the DIN (Deutsches Institut für Normung) microdilution assay. 24 and 48 h MIC of quality control strains, tested per each test run, prepared with the new inoculum method were in the range of DIN. YST and RPMI 1640 media showed similar MIC distributions for all molds tested. MIC readings at 48 versus 24 h yield 1 log(2) higher MIC values and more than 90 % of the MICs read at 24 and 48 h were within ± 2 log(2) dilution. MIC end point reading (log(2 MIC-RPMI 1640)-log(2 MIC-YST)) of both media demonstrated a tendency to slightly lower MICs with RPMI 1640 medium. This study reports the results of a new, time-saving, and easy-to-perform method for inoculum preparation for routine susceptibility testing that can be applied for all types of spore-/non-spore and hyphae-forming fungi.

First Comprehensive Evaluation of the M.I.C. Evaluator Device Compared to Etest and CLSI Broth Microdilution for MIC Testing of Aerobic Gram-Positive and Gram-Negative Bacterial Species

PubMed Central

Turnbull, L.; Brosnikoff, C.; Cloke, J.

2012-01-01

The M.I.C. Evaluator strip (Thermo Fisher Scientific, Basingstoke, United Kingdom) uses a methodology similar to that of Etest. In this first assessment of the M.I.C. Evaluator device, 409 strains of aerobic Gram-positive bacteria (staphylococci, streptococci, and enterococci) and 325 strains of Enterobacteriaceae, Pseudomonas species, and Acinetobacter species were tested by M.I.C. Evaluator strip, Etest, and broth microdilution as a reference standard. The Gram-positive bacteria included staphylococci (methicillin-resistant Staphylococcus aureus, methicillin-susceptible S. aureus, and coagulase-negative staphylococci), Streptococcus pneumoniae, beta-hemolytic streptococci and viridians group strains, vancomycin-resistant enterococci, and other enterococci. The Gram-negative bacteria included 250 strains of 60 Enterobacteriaceae species plus 50 Pseudomonas and 25 Acinetobacter species. A total of 14 antimicrobial agents (depending on the species) were included. The same methodology and reading format were used for M.I.C. Evaluator strips and Etest. Broth microdilution methodology was performed according to CLSI document M07-A8. For the clinical strains, >95% of results were plus or minus one doubling dilution for all species. There were fewer than 5% minor errors, fewer than 3% major errors, and fewer than 1% very major errors. M.I.C. Evaluator strips and Etest often reported higher MICs than the reference broth microdilution method. The M.I.C. Evaluator strips provided results comparable to those of the predicate Etest device and are of value for the accurate testing of MICs for these important pathogens. PMID:22238441

Propolis: a potential natural product to fight Candida species infections.

PubMed

Tobaldini-Valerio, Flávia K; Bonfim-Mendonça, Patricia S; Rosseto, Helen C; Bruschi, Marcos L; Henriques, Mariana; Negri, Melyssa; Silva, Sonia; Svidzinski, Terezinha Ie

2016-08-01

To evaluate the effect of propolis against Candida species planktonic cells and its counterpart's biofilms. The MIC values, time-kill curves and filamentation form inhibition were determined in Candida planktonic cells. The effect of propolis on Candida biofilms was assessed through quantification of CFUs. MIC values, ranging from 220 to 880 µg/ml, demonstrated higher efficiency on C. albicans and C. parapsilosis than on C. tropicalis cells. In addition, propolis was able to prevent Candida species biofilm's formation and eradicate their mature biofilms, coupled with a significant reduction on C. tropicalis and C. albicans filamentation. Propolis is an inhibitor of Candida virulence factors and represents an innovative alternative to fight candidiasis.

Pharmacokinetics (PK), Pharmacodynamics (PD), and PK-PD Integration of Danofloxacin in Sheep Biological Fluids

PubMed Central

Aliabadi, F. Shojaee; Landoni, M. F.; Lees, P.

2003-01-01

The fluoroquinolone antimicrobial drug danofloxacin was administered to sheep intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1.25 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of danofloxacin in serum, inflamed tissue cage fluid (exudate), and noninflamed tissue cage fluid (transudate) were established by using a tissue cage model. The in vitro and ex vivo activities of danofloxacin in serum, exudate, and transudate against a pathogenic strain of Mannheimia haemolytica were established. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 60.5, 85.6, and 45.7 h, respectively, after i.v. dosing and 55.9, 77.9, and 49.1 h, respectively, after i.m. dosing. After i.m. dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 10.8, 3.0, and 1.6, respectively. The ex vivo growth inhibition data after i.m. dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.8, 20.2, and 28.7 h, and slightly higher values were obtained for transudate and exudate. It is proposed that use of these data might provide a novel approach to the rational design of dosage schedules. PMID:12543670

Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin

PubMed Central

Yu, Xia; Wang, Guirong; Chen, Suting; Wei, Guomei; Shang, Yuanyuan; Dong, Lingling; Schön, Thomas; Moradigaravand, Danesh; Peacock, Sharon J.

2016-01-01

Antofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying its in vitro activity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinical Mycobacterium tuberculosis strains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Löwenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions of gyrA (Rv0006) and gyrB (Rv0005). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Löwenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wild-type strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective. PMID:27324769

Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria.

PubMed

Cermak, Pavel; Olsovska, Jana; Mikyska, Alexandr; Dusek, Martin; Kadleckova, Zuzana; Vanicek, Jiri; Nyc, Otakar; Sigler, Karel; Bostikova, Vanda; Bostik, Pavel

2017-11-01

Anaerobic bacteria, such as Bacteroides fragilis or Clostridium perfringens, are part of indigenous human flora. However, Clostridium difficile represents also an important causative agent of nosocomial infectious antibiotic-associated diarrhoea. Treatment of C. difficile infection is problematic, making it imperative to search for new compounds with antimicrobial properties. Hops (Humulus lupulus L.) contain substances with antibacterial properties. We tested antimicrobial activity of purified hop constituents humulone, lupulone and xanthohumol against anaerobic bacteria. The antimicrobial activity was established against B. fragilis, C. perfringens and C. difficile strains according to standard testing protocols (CLSI, EUCAST), and the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were calculated. All C. difficile strains were toxigenic and clinically relevant, as they were isolated from patients with diarrhoea. Strongest antimicrobial effects were observed with xanthohumol showing MIC and MBC values of 15-107 μg/mL, which are close to those of conventional antibiotics in the strains of bacteria with increased resistance. Slightly higher MIC and MBC values were obtained with lupulone followed by higher values of humulone. Our study, thus, shows a potential of purified hop compounds, especially xanthohumol, as alternatives for treatment of infections caused by select anaerobic bacteria, namely nosocomial diarrhoea caused by resistant strains. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Support for higher ciprofloxacin AUC 24/MIC targets in treating Enterobacteriaceae bloodstream infection.

PubMed

Zelenitsky, Sheryl A; Ariano, Robert E

2010-08-01

Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection. Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured. Forty-two cases in which ciprofloxacin was initiated within 24 h of the positive blood culture were used in the pharmacodynamic analysis. Significant factors with regard to treatment failure were low ciprofloxacin AUC(24)/MIC (P < 0.0001), high MIC (P = 0.001), male sex (P = 0.002) and low AUC(24) (P = 0.01). AUC(24)/MIC (P = 0.012) and MIC (P = 0.019) were significant variables in multivariate analyses; however, only the former remained significant (P = 0.038) after excluding two cases with ciprofloxacin-resistant isolates. An AUC(24)/MIC breakpoint of 250 was most significant, with cure rates of 91.4% (32/35) and 28.6% (2/7) in patients with values above and below this threshold, respectively (P = 0.001). The risk of ciprofloxacin treatment failure was 27.8 times (95% confidence interval, 2.1-333) greater in those not achieving an AUC(24)/MIC >or=250 (P = 0.011). Monte Carlo simulation of 5000 study subjects predicted that 0.88 of the population would achieve an AUC(24)/MIC >or=250 with standard-dose ciprofloxacin (400 mg intravenously every 12 h). This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC(24)/MIC >or=250, rather than the conventional target of >or=125. It also shows the relevance of dose selection in optimizing target attainment, with important differences among pathogens, even those with MICs within the susceptible range.

How clear-cutting affects fire severity and soil properties in a Mediterranean ecosystem.

PubMed

Francos, Marcos; Pereira, Paulo; Mataix-Solera, Jorge; Arcenegui, Victoria; Alcañiz, Meritxell; Úbeda, Xavier

2018-01-15

Forest management practices in Mediterranean ecosystems are frequently employed to reduce both the risk and severity of wildfires. However, these pre-fire treatments may influence the effects of wildfire events on soil properties. The aim of this study is to examine the short-term effects of a wildfire that broke out in 2015 on the soil properties of three sites: two exposed to management practices in different years - 2005 (site M05B) and 2015 (site M15B) - and one that did not undergo any management (NMB) and to compare their properties with those recorded in a plot (Control) unaffected by the 2015 wildfire. We analyzed aggregate stability (AS), soil organic matter (SOM) content, total nitrogen (TN), carbon/nitrogen ratio (C/N), inorganic carbon (IC), pH, electrical conductivity (EC), extractable calcium (Ca), magnesium (Mg), sodium (Na), and potassium (K), microbial biomass carbon (C mic ) and basal soil respiration (BSR). In the managed plots, a clear-cutting operation was conducted, whereby part of the vegetation was cut and left covering the soil surface. The AS values recorded at the Control site were significantly higher than those recorded at M05B, whereas the TN and SOM values at NMB were significantly higher than those recorded at M05B. IC was significantly higher at M05B than at the other plots. There were no significant differences in C/N ratio between the analyzed sites. Soil pH at M05B was significantly higher than the value recorded at the Control plot. Extractable Ca was significantly higher at NMB than at both M05B and the Control, while extractable Mg was significantly lower at M05B than at NMB. Extractable K was significantly lower at the Control than at the three fire-affected plots. C mic was significantly higher at NMB than at the Control. BSR, BSR/C and BSR/C mic values at the fire-affected sites were significantly lower than those recorded at the Control. No significant differences were identified in C mic /C. Overall, a comparison of the pre-fire treatments showed that NMB was the practice that had the least negative effects on the soil properties studied, followed by M15B, and that fire severity was highest at M05B due to the accumulation of dead plant fuel. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis, antimicrobial activity and advances in structure-activity relationships (SARs) of novel tri-substituted thiazole derivatives.

PubMed

Reddy, Guda Mallikarjuna; Garcia, Jarem Raul; Reddy, Vemulapati Hanuman; de Andrade, Ageo Meier; Camilo, Alexandre; Pontes Ribeiro, Renan Augusto; de Lazaro, Sergio Ricardo

2016-11-10

Trisubstituted thiazoles were synthesized and studied for their antimicrobial activity and supported by theoretical calculations. In addition, MIC, MBC and MFC were also tested. Moreover, the present study was analyzed to scrutinize comprehensive structure-activity relationships. In fact, LUMO orbital energy and orbital orientation was reliable to explain their antibacterial and antifungal assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound showed higher antimicrobial activity and low MIC value due to highest LUMO energy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antibiotic susceptibility profiles of Mycoplasma synoviae strains originating from Central and Eastern Europe.

PubMed

Kreizinger, Zsuzsa; Grózner, Dénes; Sulyok, Kinga M; Nilsson, Kristin; Hrivnák, Veronika; Benčina, Dušan; Gyuranecz, Miklós

2017-11-17

Mycoplasma synoviae causes infectious synovitis and respiratory diseases in chickens and turkeys and may lead to egg shell apex abnormalities in chickens; hence possesses high economic impact on the poultry industry. Control of the disease consists of eradication, vaccination or medication. The aim of the present study was to determine the in vitro susceptibility to 14 different antibiotics and an antibiotic combination of M. synoviae strains originating from Hungary and other countries of Central and Eastern Europe. Minimal inhibitory concentration (MIC) values of a total of 41 M. synoviae strains were determined by the microbroth dilution method. The strains were collected between 2002 and 2016 and originated from Hungary (n = 26), Austria (n = 3), the Czech Republic (n = 3), Slovenia (n = 3), Ukraine (n = 3), Russia (n = 2) and Serbia (n = 1). Tetracyclines (with MIC 50 values of 0.078 μg/ml, ≤0.25 μg/ml and 0.5 μg/ml for doxycycline, oxytetracycline and chlortetracycline, respectively), macrolides (with MIC 50 values of ≤0.25 μg/ml for tylvalosin, tylosin and tilmicosin), pleuromutilins (with MIC 50 values of 0.078 μg/ml and ≤0.039 μg/ml for tiamulin and valnemulin) and the combination of lincomycin and spectinomycin (MIC 50 1 μg/ml (0.333/0.667 μg/ml)) were found to be the most effective antibiotic agents against M. synoviae in vitro. High MIC values were detected in numerous strains for fluoroquinolones (with MIC 50 values of 1.25 μg/ml and 2.5 μg/ml for enrofloxacin and difloxacin), neomycin (MIC 50 32 μg/ml), spectinomycin (MIC 50 2 μg/ml), lincomycin (MIC 50 0.5 μg/ml) and florfenicol (MIC 50 4 μg/ml). Nevertheless, strains with elevated MIC values were detected for most of the applied antibiotics. In the medical control of M. synoviae infections the preliminary in vitro antibiotic susceptibility testing and the careful evaluation of the data are crucial. Based on the in vitro examinations doxycycline, oxytetracycline, tylvalosin, tylosin and pleuromutilins could be recommended for the therapy of M. synoviae infections in the region.

Correlation of MIC value and disk inhibition zone diameters in clinical Legionella pneumophila serogroup 1 isolates.

PubMed

Bruin, Jacob P; Diederen, Bram M W; Ijzerman, Ed P F; Den Boer, Jeroen W; Mouton, Johan W

2013-07-01

Routine use of disk diffusion tests for detecting antibiotic resistance in Legionella pneumophila has not been described. The goal of this study was to determine the correlation of MIC values and inhibition zone diameter (MDcorr) in clinical L. pneumophila isolates. Inhibition zone diameter of 183 L. pneumophila clinical isolates were determined for ten antimicrobials. Disk diffusion results were correlated with MICs as determined earlier with E-tests. Overall the correlation of MIC values and inhibition zone diameters (MDcorr) of the tested antimicrobials is good, and all antimicrobials showed a WT distribution. Of the tested fluoroquinolones levofloxacin showed the best MDcorr. All macrolides showed a wide MIC distribution and good MDcorr. The MDcorr for cefotaxim, doxycycline and tigecycline was good, while for rifampicin and moxifloxacin, they were not. Overall good correlation between MIC value and disk inhibition zone were found for the fluoroquinolones, macrolides and cefotaxim. Copyright © 2013 Elsevier Inc. All rights reserved.

Outcomes with daptomycin in the treatment of Staphylococcus aureus infections with a range of vancomycin MICs

PubMed Central

Crompton, Jason A.; North, Donald S.; Yoon, MinJung; Steenbergen, Judith N.; Lamp, Kenneth C.; Forrest, Graeme N.

2010-01-01

Objectives Recent recommendations by the Infectious Diseases Society of America for the treatment of Staphylococcus aureus suggest the use of alternative agents when vancomycin MIC values are ≥2 mg/L. This study examines the outcome of patients treated with daptomycin for S. aureus infections with documented vancomycin MICs. Patients and methods All patients with skin, bacteraemia and endocarditis infections due to S. aureus with vancomycin MIC values in CORE 2005–08, a retrospective, multicentre, observational registry, were studied. The outcome (cure, improved, failure or non-evaluable) was the investigator assessment at the end of daptomycin therapy. Success was defined as cure or improved. Results Five hundred and forty-seven clinically evaluable patients were identified with discrete vancomycin MIC values [MIC <2 mg/L: 451 (82%); MIC ≥2 mg/L: 96 (18%)]. The vancomycin MIC groups were well matched for patient characteristics, types of infections, first-line daptomycin use (19%) and prior vancomycin use (58%). Clinical success was reported in 94% of patients. No differences were detected in the daptomycin success rate by the vancomycin MIC group overall or by the infection type. A multivariate logistic regression also failed to identify vancomycin MIC as a predictor of daptomycin failure. Adverse event (AE) rates were not different when analysed by MIC group; both groups had ∼17% of patients with one AE. Conclusions In this diverse population, daptomycin was associated with similar outcomes for patients, regardless of whether the vancomycin MIC was categorized as <2 or ≥2 mg/L. Further studies are warranted. PMID:20554570

Role of Phragmites australis (common reed) for heavy metals phytoremediation of estuarine sediments.

PubMed

Cicero-Fernández, Diego; Peña-Fernández, Manuel; Expósito-Camargo, Jose A; Antizar-Ladislao, Blanca

2016-01-01

The ability of Phragmites australis to take up heavy metals (Co, Ni, Mo, Cd, Pb, Cr, Cu, Fe, Mn, Zn, and Hg) and other trace elements (As, Se, Ba), from estuarine sediments was investigated using a pilot plant experimental approach. Bioaccumulation (BCF) and translocation factors (TF) were calculated in vegetative and senescence periods for two populations of P. australis, from contaminated (MIC) and non-contaminated (GAL) estuarine sediments, respectively, both growing in estuarine contaminated sediment (RIA) from ría del Carmen y Boo, Santander Bay, Spain. The highest BCF values were obtained for Ni (0.43), Ba (0.43) Mo (0.36), Cr (0.35), and Cd (0.31) for plants collected from site GAL following the senescence period. The highest BCF values recorded for plants collected from MIC following the senescence period were for Mo (0.22) and Cu (0.22). Following senescence, plants collected from GAL and MIC presented TF>1 for Ni, Mo, Se, and Zn, and in addition plants collected from MIC presented TF>1 for Ba, Cr, and Mn. A substantial increase of Micedo's rhizosphere, six times higher than Galizano's rhizosphere, suggested adaptation to contaminated sediment. The evaluated communities of P. australis demonstrated their suitability for phytoremediation of heavy metals contaminated estuarine sediments.

A ten-year (2000-2009) study of antimicrobial susceptibility of bacteria that cause bovine respiratory disease complex--Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni--in the United States and Canada.

PubMed

Portis, Ellen; Lindeman, Cynthia; Johansen, Lacie; Stoltman, Gillian

2012-09-01

Bovine isolates of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, collected from 2000 to 2009, were tested for in vitro susceptibility to ceftiofur, penicillin, danofloxacin, enrofloxacin, florfenicol, tetracycline, tilmicosin, and tulathromycin. Ceftiofur remained very active against all isolates. Penicillin retained good activity against P. multocida and H. somni isolates with no appreciable changes in susceptibility or minimal inhibitory concentration (MIC) distributions with time. While there was no obvious trend, the percent of M. haemolytica that were susceptible to penicillin ranged from 40.9% to 66.7%. Danofloxacin MIC(50) and MIC(90) values for M. haemolytica and P. multocida did not change beyond a single dilution over the 6 years it was included in the testing panel. The MIC(90) for H. somni increased beyond 1 dilution. Enrofloxacin MIC(50) values for the 3 pathogens also did not change over time, unlike the MIC(90) values, which increased by at least 4-doubling dilutions. Ninety percent or more of M. haemolytica and H. somni isolates were susceptible to florfenicol, while susceptibility among P. multocida was 79% or greater. Less than 50% of the isolates tested as susceptible to tetracycline in many of the years. All 3 organisms showed declines in tilmicosin and tulathromycin MIC(50) and MIC(90) values over the years in which they were tested.

Indium (In)- and tin (Sn)-based metal induced crystallization (MIC) on amorphous germanium (α-Ge)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Dong-Ho; Park, Jin-Hong, E-mail: jhpark9@skku.edu

Highlights: • In- and Sn-based MIC phenomenon on amorphous (α)-Ge is newly reported. • The In- and Sn-MIC phenomenon respectively started at 250 °C and 400 °C. • The Sn-MIC process presents higher sheet resistance and bigger crystal grains. - Abstract: In this paper, metal-induced crystallization (MIC) phenomenon on α-Ge by indium (In) and tin (Sn) are thoroughly investigated. In- and Sn-MIC process respectively started at 250 °C and 400 °C. Compared to the previously reported MIC samples including In-MIC, Sn-MIC process presented higher sheet resistance (similar to that of SPC) and bigger crystal grains above 50 nm (slightly smallermore » than that of SPC). According to SIMS analysis, Sn atoms diffused more slowly into Ge than In at 400 °C, providing lower density of heterogeneous nuclei induced by metals and consequently larger crystal grains.« less

Biofilm formation in Malassezia pachydermatis strains isolated from dogs decreases susceptibility to ketoconazole and itraconazole.

PubMed

Jerzsele, Akos; Gyetvai, Béla; Csere, István; Gálfi, Péter

2014-12-01

Malassezia pachydermatis is a commonly isolated yeast in veterinary dermatology that can produce biofilms in vitro and in vivo, lowering its susceptibility to antimicrobial drugs. The aim of this study was to determine and compare the in vitro susceptibility of planktonic cells and biofilms of M. pachydermatis isolates to ketoconazole and itraconazole. The presence of biofilm formation was confirmed by crystal violet staining and absorbance measurement at 595 nm wavelength, and by a scanning electron microscopy method. Cell viability was determined by the Celltiter 96 Aqueous One solution assay containing a water-soluble tetrazolium compound (MTS) with absorbance measurement at 490 nm. Planktonic cell minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of ketoconazole and itraconazole were very low: MIC90 and MFC90 were 0.032 and 0.125 μg/ml for ketoconazole, while 0.063 and 0.25 μg/ml for itraconazole, respectively. Also, the half maximal effective concentrations (EC50) of itraconazole were higher for planktonic cells and biofilms compared to ketoconazole. The EC50 values of ketoconazole were 18-169 times higher and those of itraconazole 13-124 times higher for biofilms than for planktonic cells. Biofilm EC50 levels exceeded MICs 103-2060 times for ketoconazole and 84-1400 times for itraconazole. No significant difference was found between these values of the two substances. In conclusion, biofilms of all examined M. pachydermatis strains were much less susceptible to ketoconazole and itraconazole than their planktonic forms.

Antibacterial Effects of Amoxicillin-Clavulanate against Streptococcus pneumoniae and Haemophilus influenzae Strains for Which MICs Are High, in an In Vitro Pharmacokinetic Model

PubMed Central

MacGowan, Alasdair P.; Noel, Alan R.; Rogers, Chris A.; Bowker, Karen E.

2004-01-01

The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Δ24). A high 108 CFU/ml and low 106 CFU/ml initial inocula were used. Employing the Δ24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC50) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC50 was 28 to 37%, and the 80% maximum response was 32 to 48% for the Δ24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate. PMID:15215115

Antibacterial effects of amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae strains for which MICs are high, in an in vitro pharmacokinetic model.

PubMed

MacGowan, Alasdair P; Noel, Alan R; Rogers, Chris A; Bowker, Karen E

2004-07-01

The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of Streptococcus pneumoniae and two of Haemophilus influenzae, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Delta24). A high 10(8) CFU/ml and low 10(6) CFU/ml initial inocula were used. Employing the Delta24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC(50)) for S. pneumoniae was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For H. influenzae, the T>MIC EC(50) was 28 to 37%, and the 80% maximum response was 32 to 48% for the Delta24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The S. pneumoniae data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints, S. pneumoniae and H. influenzae strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate.

In vitro activity of flumequine in comparison with several other antimicrobial agents against five pathogens isolated in calves in The Netherlands.

PubMed

Mevius, D J; Breukink, H J; van Miert, A S

1990-10-01

The in vitro activity of flumequine in comparison with several other drugs was tested against 17 P. multocida, 16 P. haemolytica, 21 S. dublin, 21 S. typhimurium and 21 E. coli strains, isolated in (veal) calves in the Netherlands. The MIC50 of flumequine for the respective pasteurellas was 0.25 and 1 microgram/ml, for the salmonellas and E. coli 0.5 micrograms/ml. In comparison with flumequine, enrofloxacin and ciprofloxacin showed higher in vitro activity, with MIC50 less than or equal to 0.008 micrograms/ml for ciprofloxacin. Decreased susceptibility of the pasteurellas was found for kanamycin, neomycin, streptomycin, gentamicin, oxytetracycline and doxycycline. The MIC50 of minocycline for P. multocida was 0.5 micrograms/ml and there was no cross resistance with the other tetracyclines. P. multocida was very susceptible to ampicillin (MIC50 less than or equal to 0.03 micrograms/ml), P. haemolytica, however, was 100% resistant to this drug. Both pasteurellas were susceptible to cephalothin and approximately 50% of the strains of both bacteria were resistant to chloramphenicol. The MIC50 of either spiramycin or tylosin was greater than or equal to their respective breakpoint-MIC values. Both pasteurellas were susceptible to the combination of trimethoprim and sulphamethoxazole. However, for P. multocida, the addition of sulphamethoxazole to trimethoprim had no synergistic effect on its MIC. In comparison with trimethorpim, aditoprim was less potent. Therefore only P. multocida was susceptible to aditoprim.

The influence of study population and definition of improvement on the smallest detectable change and the minimal important change of the neck disability index.

PubMed

Schuller, Wouter; Ostelo, Raymond W J G; Janssen, Richard; de Vet, Henrica C W

2014-04-15

Reported values of the minimal important change (MIC) and the smallest detectable change (SDC) for the neck disability index (NDI) differ strongly, raising questions about the generalizability of these parameters. The SDC and the MIC are possibly influenced by the study design or by the study population. We studied the influence of the type of anchor, the definition of improvement and population characteristics on the SDC and the MIC of the NDI. A cohort study including 101 patients with non-specific, chronic neck pain. SDC and MIC were calculated using two types of external anchors. For each anchor we applied two different definitions to dichotomize the population into improved and unimproved patients. The influence of patient characteristics was assessed in relevant subgroups: patients with or without radiating pain and patients with different baseline scores. The influence of different anchors and different definitions of improvement on estimates of the SDC and the MIC was only minimal. The SDC and the MIC were similar for subgroups of patients with or without radiation, but differed strongly for subgroups of patients with higher or lower baseline scores. Our study shows that estimates of the SDC and the MIC of the NDI can be influenced by population characteristics. It is concluded that we cannot adopt a single change score to define relevant change by combining the result of previous studies.

[Antimycoplasmal activities of ofloxacin and commonly used antimicrobial agents on Mycoplasma gallisepticum].

PubMed

Takahashi, I; Yoshida, T

1989-05-01

In vitro activities of ofloxacin (OFLX), a new quinolone derivative, against 29 strains of Mycoplasma gallisepticum was compared with those of 4 commonly used antimicrobial agents, doxycycline (DOXY), tylosin (TS), spectinomycin (SPCM) and thiamphenicol (TP). Antimycoplasmal activities of the drugs were evaluated on the MIC (final MIC) and MPC (minimum mycoplasmacidal concentration) values which were determined by a broth dilution procedure. The following results were obtained. 1. The MIC90s of OFLX and DOXY were both 0.20 micrograms/ml. The MICs of TS were distributed through a wide range (less than or equal to 0.006 - 0.78 micrograms/ml), and its MIC90 was 0.78 micrograms/ml. Of 29 M. gallisepticum strains, 27.6% were recognized as TS-resistant. The MIC90 values of SPCM and TP were 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. The MIC90 of OFLX was equal to that of DOXY and 4- to 16-fold smaller than the values of the other 3 antibiotics. 2. The MPC of OFLX was the lowest among the antibiotics tested, its MPC90 value was 0.39 micrograms/ml and was followed by DOXY (1.56 micrograms/ml). The MPCs of TS were distributed in a wide range (0.012 - 3.13 micrograms/ml), and its MPC90 was 3.13 micrograms/ml. The MPC90 values of SPCM and TP were both 6.25 micrograms/ml. Therefore, the mycoplasmacidal activity of OFLX evaluated with MPC90 values was 4- to 16-fold greater than those of the other 4 antibiotics.

In vitro sensitivity of Hungarian Actinobaculum suis strains to selected antimicrobials.

PubMed

Biksi, I; Major, Andrea; Fodor, L; Szenci, O; Vetési, F

2003-01-01

In vitro antimicrobial sensitivity of 12 Hungarian isolates and the type strain ATCC 33144 of Actinobaculum suis to different antimicrobial compounds was determined both by the agar dilution and by the disc diffusion method. By agar dilution, MIC50 values in the range of 0.05-3.125 micrograms/ml were determined for penicillin, ampicillin, ceftiofur, doxycycline, tylosin, pleuromutilins, chloramphenicol, florfenicol, enrofloxacin and lincomycin. The MIC50 value of oxytetracycline and spectinomycin was 6.25 and 12.5 micrograms/ml, respectively. For ofloxacin, flumequine, neomycin, streptomycin, gentamicin, nalidixic acid, nitrofurantoin and sulphamethoxazole + trimethoprim MIC50 values were in the range of 25-100 micrograms/ml. With the disc diffusion method, all strains were sensitive to penicillin, cephalosporins examined, chloramphenicol and florfenicol, tetracyclines examined, pleuromutilins, lincomycin and tylosin. Variable sensitivity was observed for fluoroquinolones (flumequine, enrofloxacin, ofloxacin), most of the strains were susceptible to marbofloxacin. Almost all strains were resistant to aminoglycosides but most of them were sensitive to spectinomycin. A strong correlation was determined for disc diffusion and MIC results (Spearman's rho 0.789, p < 0001). MIC values of the type strain and MIC50 values of other tested strains did not differ significantly. Few strains showed a partially distinct resistance pattern for erythromycin, lincomycin and ampicillin in both methods.

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

PubMed

Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

2002-02-01

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC90 of CZOP against H. influenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval. An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.

Lemongrass-Incorporated Tissue Conditioner Against Candida albicans Culture

PubMed Central

Amornvit, Pokpong; Srithavaj, Theerathavaj

2014-01-01

Background: Tissue conditioner is applied popularly with dental prosthesis during wound healing process but it becomes a reservoir of oral microbiota, especially Candida species after long-term usage. Several antifungal drugs have been mixed with this material to control fungal level. In this study, lemongrass essential oil was added into COE-COMFORT tissue conditioner before being determined for anti-Candida efficacy. Materials and Methods: Lemongrass (Cymbopogon citratus) essential oil was primarily determined for antifungal activity against C. albicans American type culture collection (ATCC) 10231 and MIC (minimum inhibitory concentration) value by agar disk diffusion and broth microdilution methods, respectively. COE-COMFORT tissue conditioner was prepared as recommended by the manufacturer after a fixed volume of the oil at its MIC or higher concentrations were mixed thoroughly in its liquid part. Antifungal efficacy of the tissue conditioner with/without herb was finally analyzed. Results: Lemongrass essential oil displayed potent antifungal activity against C. albicans ATCC 10231and its MIC value was 0.06% (v/v). Dissimilarly, the tissue conditioner containing the oil at MIC level did not cease the growth of the tested fungus. Both reference and clinical isolates of C. albicans were completely inhibited after exposed to the tissue conditioner containing at least 0.25% (v/v) of the oil (approximately 4-time MIC). The tissue conditioner without herb or with nystatin was employed as negative or positive control, respectively. Conclusion: COE-COMFORT tissue conditioner supplemented with lemongrass essential oil obviously demonstrated another desirable property as in vitro anti-Candida efficacy to minimize the risk of getting Candidal infection. PMID:25177638

Reduced susceptibility to chlorhexidine disinfectant among New Delhi metallo-beta-lactamase-1 positive Enterobacteriaceae and other multidrug-resistant organisms: Report from a tertiary care hospital in Karachi, Pakistan.

PubMed

Mal, P B; Farooqi, J; Irfan, S; Hughes, M A; Khan, E

2016-01-01

We analysed susceptibility of multidrug-resistant organisms (MDROs) including New Delhi metallo-beta-lactamase-1 positive Enterobacteriaceae to chlorhexidine and compared results to their susceptible counterparts. Susceptibilities of chlorhexidine digluconate in a standard (CHX-S) preparation and two commercial disinfectants containing different CHX concentrations (2% w/v and 4% w/w) were performed. MDROs had narrower range of higher CHX-S minimum inhibitory concentrations (MICs) as compared to pan-sensitive organisms. The MIC values for commercial disinfectants products for MDROs were many folds higher (20-600 times), than CHX-S for in vitro use. Increasing antibiotic resistance among bacterial isolates can be an indirect marker of reduced susceptibility to chlorhexidine in hospital setting.

In vitro activity of tylvalosin against Spanish field strains of Mycoplasma hyopneumoniae.

PubMed

Tavío, M M; Poveda, C; Assunção, P; Ramírez, A S; Poveda, J B

2014-11-29

Mycoplasma hyopneumoniae is involved in the porcine enzootic pneumonia and respiratory disease complex; therefore, the search for new treatment options that contribute to the control of this organism is relevant. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of tylvalosin and 19 other antimicrobial agents against 20 Spanish field isolates of M. hyopneumoniae were determined using the broth microdilution method, with the type strain (J) as a control strain. Tylvalosin had MIC50 and MIC90 values of 0.016 and 0.06 µg/ml, respectively, and was the second-most effective of the assayed antibiotics, after valnemulin. Tiamulin, tylosin and lincomycin were also among the antibiotics with the lowest MIC50 and MIC90 values against the 20 field isolates (0.06-0.25 µg/ml). However, resistance to tylosin and spiramycin, which like tylvalosin, are 16-membered macrolides, was observed. The MIC50 and MIC90 values for ciprofloxacin and enrofloxacin ranged from 0.125 to 1 µg/ml; the corresponding values ranged from 2 to 4 µg/ml for oxytetracyline, which was the most active tetracycline. Furthermore, tylvalosin and valnemulin exhibited the highest bactericidal activities. In conclusion, the macrolide tylvalosin and the pleuromutilin valnemulin exhibited the highest in vitro antimicrobial activities against M. hyopneumoniae field isolates in comparison with the other tested antibiotics. British Veterinary Association.

Comparison of Neisseria gonorrhoeae MICs obtained by Etest and agar dilution for ceftriaxone, cefpodoxime, cefixime and azithromycin.

PubMed

Gose, Severin; Kong, Carol J; Lee, Yer; Samuel, Michael C; Bauer, Heidi M; Dixon, Paula; Soge, Olusegun O; Lei, John; Pandori, Mark

2013-12-01

We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs.

Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients

PubMed Central

van't Boveneind-Vrubleuskaya, Natasha; Seuruk, Tatiana; van Hateren, Kai; van der Laan, Tridia; Kosterink, Jos G. W.; van der Werf, Tjip S.; van Soolingen, Dick; van den Hof, Susan; Skrahina, Alena

2017-01-01

ABSTRACT Pharmacodynamics are especially important in the treatment of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to MIC (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of the treatment regimen at a dose of 15 mg/kg administered once daily. Blood samples obtained at steady state before and 1, 2, 3, 4, 7, and 12 h after drug administration were measured by validated liquid chromatography-tandem mass spectrometry. The MIC values of LFX were determined by the agar dilution method on Middlebrook 7H10 and the MGIT960 system. Twenty patients with a mean age of 31 years (interquartile range [IQR] = 27 to 35 years) were enrolled in this study. The median AUC0–24 was 98.8 mg/h/liter (IQR = 84.8 to 159.6 mg/h/liter). The MIC median value for LFX was 0.5 mg/liter with a range of 0.25 to 2.0 mg/liter, and the median fAUC0–24/MIC ratio was 109.5 (IQR = 48.5 to 399.4). In 4 of the 20 patients, the value was below the target value of ≥100. When MICs of 0.25, 0.5, 1.0, and 2.0 mg/liter were applicable, 19, 18, 3, and no patients, respectively, had an fAUC/MIC ratio that exceeded 100. We observed a large variability in AUC. An fAUC0–24/MIC of ≥100 was only observed when the MIC values for LFX were 0.25 to 0.5 mg/liter. Dosages exceeding 15 mg/kg should be considered for target attainment if exposures are assumed to be safe. (This study has been registered at ClinicalTrials.gov under registration no. NCT02169141.) PMID:28507117

Evaluation of usage of essential oils instead of spices in meat ball formulation for controlling Salmonella spp.

PubMed

Ozdikmenli, Seda; Demirel Zorba, Nukhet N

2016-03-01

The purpose of this study was to show the efficacy of essential oils (EOs) in meat balls instead of spices because of their high antimicrobial effect and to evaluate the antimicrobial effect of Origanum onites and Ocimum basilicum EOs against Salmonella Typhimurium in minced beef (20% fat) stored at 4 ℃ for seven days. This is the first study about use of O. basilicum EO in minced beef against bacterial pathogens. Both EOs inhibit microorganisms in in vitro antibacterial tests. Minimum inhibitory concentration (MIC) values of EOs were determined. The lowest MIC values were obtained with O. onites EO 0.6 µl/ml against S. Typhimurium strains. The MIC values of O. basilicum EO 0.25 µl/ml against microorganisms. Both EOs showed a significant decrease in microorganisms inoculated in minced beef at end of storage. The concentration of the both EOs at 20 µg/mg and 10 µg/mg showed stronger antimicrobial activity against bacterial cocktail of S. Typhimurium in beef; however, the higher concentrations caused alterations in the organoleptic properties of meatballs. The results of the present study indicate that O. onites and O. basilicum EOs may be used in combination with each other and different food preservation systems in meat ball formulation. © The Author(s) 2015.

Essential oil composition and antimicrobial activity of wild and cultivated Moroccan Achillea ageratum L.: a rare and threatened medicinal species.

PubMed

El Bouzidi, Laila; Abbad, Abdelaziz; Hassani, Lahcen; Fattarsi, Karine; Leach, David; Markouk, Mohammed; Legendre, Laurent; Bekkouche, Khalid

2012-03-01

The essential oils of leaves and flowers of the wild and cultivated Moroccan Achillea ageratum L., a rare and threatened medicinal species, were examined by GC/MS, and their chemical compositions were compared. At least nine components were identified in both wild and cultivated A. ageratum oils, representing more than 95% of the oils. Artemisyl acetate (62.34-78.79%), yomogi alcohol (4.89-12.40%), santolina alcohol (4.86-11.77%), and artemisia alcohol (3.36-7.04%) were the major compounds. Terpene-alcohol proportion was higher in wild A. ageratum than in cultivated A. ageratum. The antibacterial analysis showed that both oils presented high activity against all the studied Gram-positive strains in a range of MIC values from 2.55 to 7.02 mg/ml, but they appeared not effective against the tested Gram-negative ones (MIC values 20.40-41.10 mg/ml). They also exhibited remarkable antifungal activities against Candida species with MIC values ranging from 5.83 to 8.42 mg/ml. From these results, it was concluded that domestication of this threatened medicinal species using clonal propagation did not significantly affect its chemical composition and consequently its antimicrobial properties. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Application of Origanum majorana L. essential oil as an antimicrobial agent in sausage.

PubMed

Busatta, C; Vidal, R S; Popiolski, A S; Mossi, A J; Dariva, C; Rodrigues, M R A; Corazza, F C; Corazza, M L; Vladimir Oliveira, J; Cansian, R L

2008-02-01

This work reports on the antimicrobial activity in fresh sausage of marjoram (Origanum majorana L.) essential oil against several species of bacteria. The in vitro minimum inhibitory concentration (MIC) was determined for 10 selected aerobic heterotrophic bacterial species. The antimicrobial activity of distinct concentrations of the essential oil based on the highest MIC value was tested in a food system comprising fresh sausage. Batch food samples were also inoculated with a fixed concentration of Escherichia coli and the time course of the product was evaluated with respect to the action of the different concentrations of essential oil. Results showed that addition of marjoram essential oil to fresh sausage exerted a bacteriostatic effect at oil concentrations lower than the MIC, while a bactericidal effect was observed at higher oil concentrations which also caused alterations in the taste of the product.

Antimicrobial susceptibility pattern of Brachyspira intermedia isolates from European layers.

PubMed

Verlinden, Marc; Boyen, Filip; Pasmans, Frank; Garmyn, An; Haesebrouck, Freddy; Martel, An

2011-09-01

A broth microdilution method was used to determine the antimicrobial susceptibility of 20 Brachyspira intermedia isolates obtained from different layer flocks in Belgium and The Netherlands between 2008 and 2010. The antimicrobial agents used were tylosin, tilmicosin, tiamulin, valnemulin, doxycycline, and lincomycin. The minimal inhibitory concentration (MIC) distribution patterns of tylosin, tilmicosin, lincomycin, and doxycycline were bimodal, demonstrating acquired resistance against doxycycline in three strains, against the macrolides in two strains, and against lincomycin in one strain. The MICs of tiamulin and valnemulin showed a monomodal distribution, but with tailing toward the higher MIC values, possibly suggesting low-level acquired resistance in six isolates. Sequencing revealed a G1058C mutation in the 16S rRNA gene in all doxycycline-resistant strains. The strain resistant to tylosin, tilmicosin, and lincomycin had an A2058T mutation in the 23S rRNA gene.

Assessment of Minimum Inhibitory Concentrations of Telavancin by Revised Broth Microdilution Method in Phase 3 Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Clinical Isolates.

PubMed

Smart, Jennifer I; Corey, Gordon Ralph; Stryjewski, Martin E; Wang, Whedy; Barriere, Steven L

2016-12-01

The broth microdilution method (BMD) for testing telavancin minimum inhibitory concentrations (MICs) was revised (rBMD) in 2014 to improve the accuracy, precision, and reproducibility of the testing method. The aim of this study was to determine the effect of the revised method on telavancin MIC values for Staphylococcus aureus (S. aureus) clinical isolates obtained from hospital-acquired pneumonia (HAP) patients. Isolates from patients who participated in the phase 3 Assessment of Telavancin for Treatment of HAP Studies were retested using the rBMD method. Retesting of 647 isolates produced a range of telavancin MIC values from 0.015 µg/mL to 0.12 µg/mL with MIC 50/90 values of 0.06/0.06 µg/mL for the total pool of samples. For methicillin-resistant S. aureus (MRSA), MIC 50/90 values were 0.06/0.12 µg/mL. These values are up to 4-fold lower than MIC 50/90 values obtained using the original method. These results were used in part to justify lowering the telavancin breakpoints. All tested isolates remained susceptible to telavancin at the revised susceptibility breakpoint of ≤0.12 µg/mL. Overall, the clinical cure rate for microbiologically evaluable telavancin-treated patients was 78% for S. aureus, 76% for patients with MRSA, and 79% for patients with isolates with reduced susceptibility to vancomycin (MIC ≥1 µg/mL). Results from the rBMD method support the in vitro potency of telavancin against S. aureus. ATTAIN (NCT00107952 and NCT00124020). Theravance Biopharma Antibiotics, Inc.

In vitro antifungal activity of topical and systemic antifungal drugs against Malassezia species.

PubMed

Carrillo-Muñoz, Alfonso Javier; Rojas, Florencia; Tur-Tur, Cristina; de Los Ángeles Sosa, María; Diez, Gustavo Ortiz; Espada, Carmen Martín; Payá, María Jesús; Giusiano, Gustavo

2013-09-01

The strict nutritional requirements of Malassezia species make it difficult to test the antifungal susceptibility. Treatments of the chronic and recurrent infections associated with Malassezia spp. are usually ineffective. The objective of this study was to obtain in vitro susceptibility profile of 76 clinical isolates of Malassezia species against 16 antifungal drugs used for topical or systemic treatment. Isolates were identified by restriction fragment length polymorphism. Minimal inhibitory concentrations (MIC) were obtained by a modified microdilution method based on the Clinical Laboratory Standards Institute reference document M27-A3. The modifications allowed a good growth of all tested species. High in vitro antifungal activity of most tested drugs was observed, especially triazole derivatives, except for fluconazole which presented the highest MICs and widest range of concentrations. Ketoconazole and itraconazole demonstrated a great activity. Higher MICs values were obtained with Malassezia furfur indicating a low susceptibility to most of the antifungal agents tested. Malassezia sympodialis and Malassezia pachydermatis were found to be more-susceptible species than M. furfur, Malassezia globosa, Malassezia slooffiae and Malassezia restricta. Topical substances were also active but provide higher MICs than the compounds for systemic use. The differences observed in the antifungals activity and interspecies variability demonstrated the importance to studying the susceptibility profile of each species to obtain reliable information for defining an effective treatment regimen. © 2013 Blackwell Verlag GmbH.

Antibiotic susceptibility profiles of Mycoplasma sp. 1220 strains isolated from geese in Hungary.

PubMed

Grózner, Dénes; Kreizinger, Zsuzsa; Sulyok, Kinga M; Rónai, Zsuzsanna; Hrivnák, Veronika; Turcsányi, Ibolya; Jánosi, Szilárd; Gyuranecz, Miklós

2016-08-19

Mycoplasma sp. 1220 can induce inflammation primarily in the genital and respiratory tracts of waterfowl, leading to serious economic losses. Adequate housing and appropriate antibiotic treatment are promoted in the control of the disease. The aim of the present study was to determine the in vitro susceptibility to thirteen different antibiotics and an antibiotic combination of thirty-eight M. sp. 1220 strains isolated from geese and a duck in several parts of Hungary, Central Europe between 2011 and 2015. High MIC50 values were observed in the cases of tilmicosin (>64 μg/ml), oxytetracycline (64 μg/ml), norfloxacin (>10 μg/ml) and difloxacin (10 μg/ml). The examined strains yielded the same MIC50 values with spectinomycin, tylosin and florfenicol (8 μg/ml), while enrofloxacin (MIC50 5 μg/ml), doxycycline (MIC50 5 μg/ml), lincomycin (MIC50 4 μg/ml) and lincomycin-spectinomycin (1:2) combination (MIC50 4 μg/ml) inhibited the growth of the bacteria with lower concentrations. Tylvalosin (MIC50 0.5 μg/ml) and two pleuromutilins (tiamulin MIC50 0.625 μg/ml; valnemulin MIC50 ≤ 0.039 μg/ml) were found to be the most effective drugs against M. sp. 1220. However, strains with elevated MIC values were detected for all applied antibiotics. Valnemulin, tiamulin and tylvalosin were found to be the most effective antibiotics in the study. Increasing resistance was observed in the cases of several antibiotics. The results highlight the importance of testing Mycoplasma species for antibiotic susceptibility before therapy.

Susceptibility of vancomycin-resistant and -sensitive Enterococcus faecium obtained from Danish hospitals to benzalkonium chloride, chlorhexidine and hydrogen peroxide biocides.

PubMed

Alotaibi, Sulaiman M I; Ayibiekea, Alafate; Pedersen, Annemette Frøling; Jakobsen, Lotte; Pinholt, Mette; Gumpert, Heidi; Hammerum, Anette M; Westh, Henrik; Ingmer, Hanne

2017-12-01

In Danish hospitals, the number of infections caused by vancomycin-resistant Enterococcus faecium (VRE faecium) has dramatically increased in recent years. Hospital disinfectants are essential in eliminating pathogenic microorganisms, and reduced susceptibility may contribute to hospital-associated infections. We have addressed whether clinical VRE faecium display decreased biocide susceptibility when compared to vancomycin-sensitive Enterococcus faecium (VSE faecium) isolates. In total 12 VSE faecium and 37 VRE faecium isolates obtained from Danish hospitals over an extended time period were tested for susceptibility towards three commonly applied biocides, namely benzalkonium chloride, chlorhexidine and hydrogen peroxide. For benzalkonium chloride, 89 % of VRE faecium strains had a minimal inhibitory concentration (MIC) of 8 mg l -1 , whereas for VSE faecium, only 25 % of the strains had an MIC of 8 mg l -1 . For chlorhexidine, the MIC of 95 % of VRE faecium strains was 4 mg l -1 or higher, while only 33 % of VSE faecium strains displayed MIC values at the same level. In contrast, both VRE and VSE faecium displayed equal susceptibility to hydrogen peroxide, but a higher minimal bactericidal concentration (MBC) was found for the former. The efflux activity was also assessed, and this was generally higher for the VRE faecium strains compared to VSE faecium. VRE faecium from Danish hospitals demonstrated decreased susceptibility towards benzalkonium chloride and chlorhexidine compared to VSE faecium, where the use of chlorhexidine is particularly heavy in the hospital environment. These findings suggest that biocide tolerance may characterize VRE faecium isolated in Danish hospitals.

Preliminary antifungal activity assay of selected chlorine-containing derivatives of xanthone and phenoxyethyl amines.

PubMed

Klesiewicz, Karolina; Żelaszczyk, Dorota; Trojanowska, Danuta; Bogusz, Bożena; Małek, Marianna; Waszkielewicz, Anna; Szkaradek, Natalia; Karczewska, Elżbieta; Marona, Henryk; Budak, Alicja

2018-06-20

The aim of this study was to preliminary evaluate antifungal activity diverse group of chlorine-containing xanthone and phenoxyethyl amine derivatives - and to select most promising compounds for further studies. The antifungal efficacy of 16 compounds was tested with qualitative and quantitative methods against both reference and clinical strains of dermatophytes, moulds and yeasts. The disc-diffusion method has demonstrated that from 16 tested compounds, 7 possess good antifungal activity against dermatophytes and/or moulds while none of them has shown good efficacy against yeasts or bacterial strains. The most active compounds (2, 4, 10, 11, 12, 15, 16) were tested quantitatively by broth dilution method to obtain MIC values. The MIC values against dermatophytes ranged from 8 to 64 μg/mL. Compound 2 was the most active one against dermatophytes (MIC 50 and MIC 90 were 8 μg/mL). The MIC values for moulds ranged from 16 to 256 μg/mL. Compound 4 was the most active one against moulds, with MIC 50 and MIC 90 values amounting to 32 μg/mL. Among the tested compounds, compound 4 (derivative of xanthone) was the most active one and expressed good antifungal efficacy against clinical strains of dermatophytes and moulds. However, another xanthone derivative (compound 2) was the most active and selective against dermatophytes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Characterization of resistance to tetracyclines and aminoglycosides of sheep mastitis pathogens: study of the effect of gene content on resistance.

PubMed

Lollai, S A; Ziccheddu, M; Duprè, I; Piras, D

2016-10-01

Mastitis causes economic losses and antimicrobials are frequently used for mastitis treatment. Antimicrobial resistance surveys are still rare in the ovine field and characterization of strains is important in order to acquire information about resistance and for optimization of therapy. Bacterial pathogens recovered in milk samples from mastitis-affected ewes were characterized for resistance to tetracyclines and aminoglycosides, members of which are frequently used antimicrobials in small ruminants. A total of 185 strains of staphylococci, streptococci, and enterococci, common mastitis pathogens, were tested for minimal inhibitory concentration (MIC) to tetracycline, doxycycline, minocycline, gentamicin, kanamycin, streptomycin, and for resistance genes by PCR. Effects of different tet genes arrangements on MICs were also investigated. Staphylococci expressed the lowest MIC for tetracycline and tet(K) was the most common gene recovered; tet(M) and tet(O) were also found. Gene content was shown to influence the tetracycline MIC values. Enterococci and streptococci showed higher MICs to tetracyclines and nonsusceptible strains always harboured at least one ribosomal protection gene (MIC above 8 μg ml(-1) ). Streptococci often harboured two or more tet determinants. As regards the resistance to aminoglycosides, staphylococci showed the lowest gentamicin and kanamycin median MIC along with streptomycin high level resistant (HLR) strains (MIC >1024 μg ml(-1) ) all harbouring str gene. The resistance determinant aac(6')-Ie-aph(2″)-Ia was present in few strains. Streptococci were basically nonsusceptible to aminoglycosides but neither HLR isolates nor resistance genes were detected. Enterococci revealed the highest MICs for gentamicin; two str harbouring isolates were shown to be HLR to streptomycin. Evidence was obtained for the circulation of antimicrobial-resistant strains and genes in sheep dairy farming. Tetracycline MIC of 64 μg ml(-1) and high-level resistance were detected for streptomycin (MIC >1024 μg ml(-1) ), so that effectiveness of common treatments may be at risk. © 2016 The Society for Applied Microbiology.

Tolerance to chitosan by Trichoderma species is associated with low membrane fluidity.

PubMed

Zavala-González, Ernesto A; Lopez-Moya, Federico; Aranda-Martinez, Almudena; Cruz-Valerio, Mayra; Lopez-Llorca, Luis Vicente; Ramírez-Lepe, Mario

2016-07-01

The effect of chitosan on growth of Trichoderma spp., a cosmopolitan genus widely exploited for their biocontrol properties was evaluated. Based on genotypic (ITS of 18S rDNA) characters, four isolates of Trichoderma were identified as T. pseudokoningii FLM16, T. citrinoviride FLM17, T. harzianum EZG47, and T. koningiopsis VSL185. Chitosan reduces radial growth of Trichoderma isolates in concentration-wise manner. T. koningiopsis VSL185 was the most chitosan tolerant isolate in all culture media amended with chitosan (0.5-2.0 mg ml(-1) ). Minimal Inhibitory Concentration (MIC) and Minimal Fungicidal Concentration (MFC) were determined showing that T. koningiopsis VSL185 displays higher chitosan tolerance with MIC value >2000 μg ml(-1) while for other Trichoderma isolates MIC values were around 10 μg ml(-1) . Finally, free fatty acid composition reveals that T. koningiopsis VSL185, chitosan tolerant isolate, displays lower linolenic acid (C18:3) content than chitosan sensitive Trichoderma isolates. Our findings suggest that low membrane fluidity is associated with chitosan tolerance in Trichoderma spp. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of Neisseria gonorrhoeae MICs Obtained by Etest and Agar Dilution for Ceftriaxone, Cefpodoxime, Cefixime and Azithromycin.

PubMed

Gose, Severin; Kong, Carol J; Lee, Yer; Samuel, Michael C; Bauer, Heidi M; Dixon, Paula; Soge, Olusegun O; Lei, John; Pandori, Mark

2013-10-24

We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs. © 2013. Published by Elsevier B.V. All rights reserved.

Platismatia glaucia and Pseudevernia furfuracea lichens as sources of antioxidant, antimicrobial and antibiofilm agents.

PubMed

Mitrovic, Tatjana; Stamenkovic, Slaviša; Cvetkovic, Vladimir; Radulovic, Niko; Mladenovic, Marko; Stankovic, Milan; Topuzovic, Marina; Radojevic, Ivana; Stefanovic, Olgica; Vasic, Sava; Comic, Ljiljana

2014-01-01

The antioxidative, antimicrobial and antibiofilm potentials of acetone, ethyl acetate and methanol extracts of lichen species Platismatia glauca and Pseudevernia furfuracea were evaluated. The phytochemical analysis by GC, GC/MS and NMR revealed caperatic acid, atraric acid, atranorin and chloroatranorin as the predominant compounds in Platismatia glauca. Atraric acid, olivetoric acid, atranorin and chloroatranorin were the major constituents in Pseudevernia furfuracea. The strong antioxidant capacities of the Platismatia glauca and Pseudevernia furfuracea extracts were assessed by their total phenolic and flavonoid contents and DPPH scavenging activities. The methanol extracts of both species exhibited the strongest antioxidant activities with the highest IC50 value for Pseudevernia furfuracea (95.33 µg/mL). The lichen extracts demonstrated important antibacterial activities against 11 bacterial strains with detectable MIC values from 0.08 mg/mL to 2.5 mg/mL for Platismatia glauca and from 0.005 mg/mL to 2.5 mg/mL for Pseudevernia furfuracea. While the antibacterial activities of Pseudevernia furfuracea were solvent-independent, the acetone and ethyl acetate extracts of Platismatia glauca showed higher antibacterial activities compared to its methanol extract. The methanol extracts of both species demonstrated significant antifungal activities against 9 fungal strains with detectable MIC values from 0.04 mg/mL to 2.5 mg/mL. The best antifungal activities were determined against Candida species in Pseudevernia furfuracea extracts with remarkable MIC values which were lower than the MIC values of the positive contol fluconazole. The acetone and ethyl acetate extracts of Platismatia glauca showed better antibiofilm activities on Staphylococcus aureus and Proteus mirabilis with BIC value at 0.63 mg/mL then its methanol extract. On the other hand, the methanol extract of Pseudevernia furfuracea was more potent with BIC value at 1.25 mg/mL on Staphylococcus aureus and 0.63 mg/mL on Proteus mirabilis compared to other types of extracts. Our study indicates a possible use of lichens Platismatia glauca and Pseudevernia furfuracea as natural antioxidants and preservatives in food, pharmaceutical and cosmetic industry.

Platismatia glaucia and Pseudevernia furfuracea lichens as sources of antioxidant, antimicrobial and antibiofilm agents

PubMed Central

Mitrovic, Tatjana; Stamenkovic, Slaviša; Cvetkovic, Vladimir; Radulovic, Niko; Mladenovic, Marko; Stankovic, Milan; Topuzovic, Marina; Radojevic, Ivana; Stefanovic, Olgica; Vasic, Sava; Comic, Ljiljana

2014-01-01

The antioxidative, antimicrobial and antibiofilm potentials of acetone, ethyl acetate and methanol extracts of lichen species Platismatia glauca and Pseudevernia furfuracea were evaluated. The phytochemical analysis by GC, GC/MS and NMR revealed caperatic acid, atraric acid, atranorin and chloroatranorin as the predominant compounds in Platismatia glauca. Atraric acid, olivetoric acid, atranorin and chloroatranorin were the major constituents in Pseudevernia furfuracea. The strong antioxidant capacities of the Platismatia glauca and Pseudevernia furfuracea extracts were assessed by their total phenolic and flavonoid contents and DPPH scavenging activities. The methanol extracts of both species exhibited the strongest antioxidant activities with the highest IC50 value for Pseudevernia furfuracea (95.33 µg/mL). The lichen extracts demonstrated important antibacterial activities against 11 bacterial strains with detectable MIC values from 0.08 mg/mL to 2.5 mg/mL for Platismatia glauca and from 0.005 mg/mL to 2.5 mg/mL for Pseudevernia furfuracea. While the antibacterial activities of Pseudevernia furfuracea were solvent–independent, the acetone and ethyl acetate extracts of Platismatia glauca showed higher antibacterial activities compared to its methanol extract. The methanol extracts of both species demonstrated significant antifungal activities against 9 fungal strains with detectable MIC values from 0.04 mg/mL to 2.5 mg/mL. The best antifungal activities were determined against Candida species in Pseudevernia furfuracea extracts with remarkable MIC values which were lower than the MIC values of the positive contol fluconazole. The acetone and ethyl acetate extracts of Platismatia glauca showed better antibiofilm activities on Staphylococcus aureus and Proteus mirabilis with BIC value at 0.63 mg/mL then its methanol extract. On the other hand, the methanol extract of Pseudevernia furfuracea was more potent with BIC value at 1.25 mg/mL on Staphylococcus aureus and 0.63 mg/mL on Proteus mirabilis compared to other types of extracts. Our study indicates a possible use of lichens Platismatia glauca and Pseudevernia furfuracea as natural antioxidants and preservatives in food, pharmaceutical and cosmetic industry. PMID:26417313

Comparative Pharmacodynamics of Telavancin and Vancomycin in the Neutropenic Murine Thigh and Lung Infection Models against Staphylococcus aureus

PubMed Central

Lepak, Alexander J.; Zhao, Miao

2017-01-01

ABSTRACT The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four Staphylococcus aureus strains were included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed that penetration into the ELF mirrored the percentage of the free fraction (the fraction not protein bound) in plasma for each drug. Telavancin (0.3125 to 80 mg/kg/6 h) and vancomycin (0.3125 to 1,280 mg/kg/6 h) were administered by the subcutaneous route in treatment studies. Dose-dependent bactericidal activity against all four strains was observed in both models. A sigmoid maximum-effect model was used to determine the area under the concentration-time curve (AUC)/MIC exposure associated with net stasis and 1-log10 kill relative to the burden at the start of therapy. The 24-h plasma free drug AUC (fAUC)/MIC values associated with stasis and 1-log kill were remarkably congruent. Net stasis for telavancin was noted at fAUC/MIC values of 83 and 40.4 in the thigh and lung, respectively, and 1-log kill was noted at fAUC/MIC values of 215 and 76.4, respectively. For vancomycin, the fAUC/MIC values for stasis were 77.9 and 45.3, respectively, and those for 1-log kill were 282 and 113, respectively. The 24-h ELF total drug AUC/MIC targets in the lung model were very similar to the 24-h plasma free drug AUC/MIC targets for each drug. Integration of human pharmacokinetic data for telavancin, the results of the MIC distribution studies, and the pharmacodynamic targets identified in this study suggests that the current dosing regimen of telavancin is optimized to obtain drug exposures sufficient to treat S. aureus infections. PMID:28416551

Antimicrobial susceptibilities and molecular typing of neisseria gonorrhoeae isolates at a medical centre in Taiwan, 2001-2013 with an emphasis on high rate of azithromycin resistance among the isolates.

PubMed

Liu, Yen-Hung; Huang, Yu-Tsung; Liao, Chun-Hsing; Hsueh, Po-Ren

2018-05-01

A high prevalence of gonococcal resistance to various antimicrobials and Neisseria gonorrhoeae isolates exhibiting resistance to extended-spectrum cephalosporins have been reported in the past few decades. A total of 226 N. gonorrhoeae isolates obtained from the National Taiwan University Hospital from 2001 to 2013 were evaluated. The minimum inhibitory concentrations (MICs) of the isolates to antimicrobials were determined by the agar dilution method and interpreted using the 2017 clinical breakpoints or epidemiological cut-off values recommended by the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). The genetic relatedness of these isolates was determined by multilocus sequence typing. None of the isolates was resistant to ceftriaxone and cefotaxime, and the resistance rates to cefixime, spectinomycin, cefpodoxime, ciprofloxacin, and penicillin were 0.4%, 0.4%, 13.3%, 91.6%, and 87.6%, respectively. The rate of isolates resistant to azithromycin was 14.6% (EUCAST criteria), which is higher than in previous surveillance studies. A total of 57 sequence types (ST) were identified, and ST1901, ST7365, and ST1927 prevailed. Isolates of ST8143 emerged after 2011. ST1901 isolates had relatively higher MIC values for ceftriaxone and azithromycin than those of the other STs. In conclusion, ceftriaxone remains an effective drug of choice for gonorrhoeal management in Taiwan. High rates of azithromycin resistance among N. gonorrhoeae isolates were found. The circulating ST1901 strains with high MIC values for ceftriaxone and azithromycin and the emerging ST8143 strains were alarming. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Intrapulmonary pharmacokinetics and pharmacodynamics of high-dose levofloxacin in healthy volunteer subjects.

PubMed

Conte, John E; Golden, Jeffrey A; McIver, Marina; Zurlinden, Elisabeth

2006-08-01

The objective of this study was to determine the plasma and intrapulmonary pharmacokinetic parameters of intravenously administered levofloxacin in healthy volunteers. Three doses of either 750 mg or 1000 mg levofloxacin were administered intravenously to 4 healthy adult subjects (750 mg) to 20 healthy adult subjects divided into five groups of 4 subjects (1000 mg). Standardised bronchoscopy and timed bronchoalveolar lavage (BAL) were performed following administration of the last dose. Blood was obtained for drug assay prior to drug administration and at the time of BAL. Levofloxacin was measured in plasma, BAL fluid and alveolar cells (ACs) using a sensitive and specific combined high-performance liquid chromatographic tandem mass spectrometric technique (HPLC/MS/MS). Plasma, epithelial lining fluid (ELF) and AC pharmacokinetics were derived using non-compartmental methods. The maximum plasma drug concentration to minimum inhibitory concentration ratio (C(max)/MIC(90)) and the area under the drug concentration curve to minimum inhibitory concentration ratio (AUC/MIC(90)) during the dosing interval were calculated for potential respiratory pathogens with MIC(90) values from 0.03 microg/mL to 2 microg/mL. In the 1000 mg dose group, the C(max) (mean+/-standard deviation (S.D.)), AUC(0-8h) and half-life were: for plasma, 9.2+/-1.9 microg/mL, 103.6 microg h/mL and 7.45 h; for ELF, 25.8+/-7.9 microg/mL, 279.1 microg h/mL and 8.10h; and for ACs, 51.8+/-26.2 microg/mL, 507.5 microg h/mL and 14.32 h. In the 750 mg dose group, the C(max) values in plasma, ELF and ACs were 5.7+/-0.4, 28.0+/-23.6 and 34.2+/-18.7 microg/mL, respectively. Levofloxacin concentrations were significantly higher in ELF and ACs than in plasma at all time points. For pathogens commonly associated with community-acquired pneumonia, C(max)/MIC(90) ratios in ELF ranged from 12.9 for Mycoplasma pneumoniae to 859 for Haemophilus influenzae, and AUC/MIC(90) ratios ranged from 139 to 9303, respectively. The C(max)/MIC(90) ratios in ACs ranged from 25.9 for M. pneumoniae to 1727 for H. influenzae, and AUC/MIC(90) ratios ranged from 254 to 16917, respectively. The C(max)/MIC(90) and AUC/MIC(90) ratios provide a pharmacokinetic rationale for once-daily administration of a 1000 mg dose of levofloxacin and are favourable for the treatment of community-acquired respiratory pathogens.

Semisynthetic Phenol Derivatives Obtained from Natural Phenols: Antimicrobial Activity and Molecular Properties.

PubMed

Pinheiro, Patrícia Fontes; Menini, Luciana Alves Parreira; Bernardes, Patrícia Campos; Saraiva, Sérgio Henriques; Carneiro, José Walkimar Mesquita; Costa, Adilson Vidal; Arruda, Társila Rodrigues; Lage, Mateus Ribeiro; Gonçalves, Patrícia Martins; Bernardes, Carolina de Oliveira; Alvarenga, Elson Santiago; Menini, Luciano

2018-01-10

Semisynthetic phenol derivatives were obtained from the natural phenols: thymol, carvacrol, eugenol, and guaiacol through catalytic oxychlorination, Williamson synthesis, and aromatic Claisen rearrangement. The compounds characterization was carried out by 1 H NMR, 13 C NMR, and mass spectrometry. The natural phenols and their semisynthetic derivatives were tested for their antimicrobial activity against the bacteria: Staphylococcus aureus, Escherichia coli, Listeria innocua, Pseudomonas aeruginosa, Salmonella enterica Typhimurium, Salmonella enterica ssp. enterica, and Bacillus cereus. Minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were determined using concentrations from 220 to 3.44 μg mL -1 . Most of the tested compounds presented MIC values ≤220 μg mL -1 for all the bacteria used in the assays. The molecular properties of the compounds were computed with the PM6 method. Through principle components analysis, the natural phenols and their semisynthetic derivatives with higher antimicrobial potential were grouped.

Inhibitory Activity of Avocado Seed Fatty Acid Derivatives (Acetogenins) Against Listeria Monocytogenes.

PubMed

Salinas-Salazar, Carmen; Hernández-Brenes, Carmen; Rodríguez-Sánchez, Dariana Graciela; Castillo, Elena Cristina; Navarro-Silva, Jesús Manuel; Pacheco, Adriana

2017-01-01

High standards regarding Listeria monocytogenes control and consumer demands for food products without synthetic additives represent a challenge to food industry. We determined the antilisterial properties of an enriched acetogenin extract (EAE) from avocado seed, compared it to two commercial antimicrobials (one enriched in avocado acetogenins), and tested purified molecules. Acetogenin composition in pulp and seed of Hass avocado was quantified. EAE were obtained by two sequential centrifuge partition chromatography separations and molecules purified by preparative chromatography and quantified by HPLC-MS-TOF and HPLC-PDA. Avocado seed extracts which are the following two: 1) EAE and 2) the commercially available antimicrobial Avosafe®, presented similar inhibition zones and chemical profiles. Minimum inhibitory concentration (MIC) values of extracts and two isolated acetogenins varied between 7.8 and 15.6 mg/L, were effective at 37 and 4 °C, and showed a bactericidal effect probably caused by increased membrane permeability and lytic effects, evidenced by flow cytometry at 10 and 100× MIC. Activity was comparable to Mirenat®. Most potent acetogenins were Persenone C (5) and A (6), and AcO-avocadenyne (1), the latter exclusively present in seed. Common features of bioactive molecules were the acetyl moiety and multiple unsaturations (2 to 3) in the aliphatic chain, some persenones also featured a trans-enone group. Seeds contained 1.6 times higher levels of acetogenins than pulp (5048.1 ± 575.5 and 3107.0 ± 207.2 mg/kg fresh weight, respectively), and total content in pulp was 199 to 398 times higher than MIC values. Therefore, acetogenin levels potentially consumed by humans are higher than inhibitory concentrations. Results document properties of avocado seed acetogenins as natural antilisterial food additives. © 2016 Institute of Food Technologists®.

Efficacy of simulated cefditoren versus amoxicillin-clavulanate free concentrations in countering intrastrain ftsI gene diffusion in Haemophilus influenzae.

PubMed

González, Natalia; Aguilar, Lorenzo; Sevillano, David; Giménez, Maria-Jose; Alou, Luis; Cafini, Fabio; Torrico, Martha; López, Ana-Maria; Coronel, Pilar; Prieto, Jose

2011-06-01

This study explores the effects of cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in β-lactamase-positive (BL⁺) and β-lactamase-negative (BL⁻) Haemophilus influenzae. DNA from β-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNA(BLNAR)) and from β-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNA(BLPACR)) isolates was extracted and added to a 10⁷-CFU/ml suspension of one BL⁺ strain (CDN MIC, 0.007 μg/ml; AMC MIC, 1 μg/ml) or one BL⁻ strain (CDN MIC, 0.015 μg/ml; AMC MIC, 0.5 μg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL⁻ and BL⁺ total populations and the BL⁻ recombined population increased (from ≈3 log₁₀ to 4.5 to 5 log₁₀), while the BL⁺ recombined population was maintained in simulations with DNA(BLPACR) and was decreased by ≈2 log₁₀ with DNA(BLNAR). CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ft>MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL⁻ strains (ft>MIC, 74.0%) in DNA(BLNAR) and DNA(BLPACR) simulations, with a small final recombined population (MIC, 4 μg/ml; ft>MIC, 30.7%) in DNA(BLPACR) simulations. When AMC was used against the BL⁺ strain (in DNA(BLNAR) or DNA(BLPACR) simulations), the bacterial load was reduced ≈2 log₁₀ (ft>MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 μg/ml; ft>MIC, 0%) in DNA(BLNAR) and DNA(BLPACR) simulations, respectively. AMC, but not CDN, unmasked BL⁺ recombined populations obtained by transformation. ft>MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.

[Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from animals to ofloxacin and commonly used antimicrobial agents].

PubMed

Takahashi, I; Yoshida, T; Higashide, Y; Sakano, T

1990-01-01

Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from chickens, pigs and cattle to ofloxacin (OFLX) and commonly used antimicrobial agents were investigated. 1. E. coli (28 isolates) demonstrated the highest level of susceptibility of OFLX (MIC 0.10-0.39 micrograms/ml for all the isolates) among all the test drugs. Commonly used antimicrobial agents to which these isolates responded with relatively high susceptibilities (MIC50 0.78-6.25 micrograms/ml) included oxolinic acid (OXA), ampicillin (ABPC), kanamycin (KM) and chloramphenicol (CP) with their MIC50 values in the increasing order as above. Drugs to which these isolates responded with moderate to weak susceptibilities (MIC50 25 approximately greater than 800 micrograms/ml) were doxycycline (DOXY), streptomycin (SM), spectinomycin (SPCM) and sulfadimethoxine (SDMX) in the increasing order of MIC50. E. coli isolates with resistances to all the test drugs other than OFLX and OXA amounted to 7.1-57.1% of the isolates examined and 20 isolates (71.4%) in total. 2. Susceptibilities to OFLX and 4 existing pyridonecarboxylic acid derivatives of E. coli (48 samples) isolated recently from diarrheal pigs were compared. When evaluated in terms of MIC50, the values of OFLX and norfloxacin were both 0.10 micrograms/ml. The values increased by differences of 0.39-3.13 micrograms/ml in an order of OXA, pipemidic acid and nalidixic acid. 3. Salmonella (28 isolates) demonstrated the highest level of susceptibility to OFLX (MIC 0.20-0.39 micrograms/ml for all the isolates) among all the test drugs. The drugs to which these isolates responded with relatively high to moderate susceptibilities (MIC50 0.78-12.5 micrograms/ml) included ABPC, OXA, DOXY, KM, CP and SM with their MIC50 values increasing in this order. The drugs to which the isolates responded with low susceptibilities (MIC50 above 100 micrograms/ml) were SPCM and SDMX. Of all the 28 Salmonella isolates tested, 7.1-32.1% were resistant to all the test drugs other than OFLX and OXA. These resistant isolates amounted to a total of 12 isolates (42.9%). 4. S. aureus (28 isolates) were highly susceptible to OFLX (MIC50 and MIC90 were both 0.78 micrograms/ml). Commonly used antimicrobial agents to which the isolates responded with high to relatively high susceptibilities (MIC50 0.10-6.25 micrograms/ml) were, in the increasing order of MIC50: DOXY, ABPC, tylosin, tiamulin, KM, OXA and CP. Drugs with moderate to low bacterial susceptibilities (MIC50 12.5-100 microns/ml) were SD, SDMX and SPCM. Isolates resistant to all the test drugs except OFLX and SDMX amounted to 3.6-50% of the 28 isolates examined and they totalled 20 isolates (71.4%).(ABSTRACT TRUNCATED AT 400 WORDS)

Antimicrobial and antioxidant activity of kaempferol rhamnoside derivatives from Bryophyllum pinnatum

PubMed Central

2012-01-01

Background Bryophyllum pinnatum (Lank.) Oken (Crassulaceae) is a perennial succulent herb widely used in traditional medicine to treat many ailments. Its wide range of uses in folk medicine justifies its being called "life plant" or "resurrection plant", prompting researchers' interest. We describe here the isolation and structure elucidation of antimicrobial and/or antioxidant components from the EtOAc extract of B. pinnatum. Results The methanol extract displayed both antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 32 to 512 μg/ml and antioxidant property with an IC50 value of 52.48 μg/ml. Its partition enhanced the antimicrobial activity in EtOAc extract (MIC = 16-128 μg/ml) and reduced it in hexane extract (MIC = 256-1024 μg/ml). In addition, this process reduced the antioxidant activity in EtOAc and hexane extracts with IC50 values of 78.11 and 90.04 μg/ml respectively. Fractionation of EtOAc extract gave seven kaempferol rhamnosides, including; kaempferitrin (1), kaempferol 3-O-α-L-(2-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (2), kaempferol 3-O-α-L-(3-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (3), kaempferol 3-O-α-L-(4-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (4), kaempferol 3-O-α-D- glucopyranoside-7-O-α-L-rhamnopyranoside (5), afzelin (6) and α-rhamnoisorobin (7). All these compounds, except 6 were isolated from this plant for the first time. Compound 7 was the most active, with MIC values ranging from 1 to 2 μg/ml and its antioxidant activity (IC50 = 0.71 μg/ml) was higher than that of the reference drug (IC50 = 0.96 μg/ml). Conclusion These findings demonstrate that Bryophyllum pinnatum and some of its isolated compounds have interesting antimicrobial and antioxidant properties, and therefore confirming the traditional use of B. pinnatum in the treatment of infectious and free radical damages. PMID:22433844

A fast and feasible method for Br and I determination in whole egg powder and its fractions by ICP-MS.

PubMed

Toralles, Isis Gonçalves; Coelho, Gilberto Silva; Costa, Vanize Cadeira; Cruz, Sandra Meinen; Flores, Erico Marlon Moraes; Mesko, Marcia Foster

2017-04-15

A method for Br and I determination in whole egg powder and its fractions (egg white and yolk) was developed by combining microwave-induced combustion (MIC) and inductively coupled plasma mass spectrometry (ICP-MS). Using the MIC method, 350mg of whole egg powder and its fractions were efficiently digested using 50mmolL -1 NH 4 OH as an absorbing solution. The limits of detection for Br and I using the MIC method followed by ICP-MS determination were 0.039 and 0.015μgg -1 , respectively. Using the proposed method, agreements with the reference values between 97 and 104% for Br and I were obtained by analysis of reference material NIST 8435. Finally, it was possible to observe that Br concentration (4.59-5.29μgg -1 ) was higher than I (0.150-2.28μgg -1 ) for all the evaluated samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune protection of microneme 7 (EmMIC7) against Eimeria maxima challenge in chickens.

PubMed

Huang, Jingwei; Zhang, Zhenchao; Li, Menghui; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

2015-10-01

In the present study, the immune protective effects of recombinant microneme protein 7 of Eimeria maxima (rEmMIC7) and a DNA vaccine encoding this antigen (pVAX1-EmMIC7) on experimental challenge were evaluated. Two-week-old chickens were randomly divided into five groups. Experimental groups of chickens were immunized with 100 μg DNA vaccine pVAX1-MIC7 or 200 μg rEmMIC7, while control groups of chickens were injected with pVAX1 plasmid or sterile phosphate buffered saline (PBS). The results showed that the anti-EmMIC7 antibody titres in chickens of both rEmMIC7 and pVAX1-MIC7 groups were significantly higher as compared to PBS and pVAX1 control (P < .05). The splenocytes from both vaccinated groups of chickens displayed significantly greater proliferation response compared with the controls (P < .05). Serum from chickens immunized with pVAX1-MIC7 and rEmMIC7 displayed significantly high levels of interleukin-2, interferon-γ, IL-10, IL-17, tumour growth factor-β and IL-4 (P < .05) compared to those of negative controls. The challenge experiment results showed that both the recombinant antigen and the DNA vaccine could obviously alleviate jejunum lesions, body weight loss and enhance oocyst decrease ratio. The anti-coccidial index (ACI) of the pVAX1-MIC7 group was 167.84, higher than that of the recombinant MIC7 protein group, 167.10. Our data suggested that immunization with EmMIC7 was effective in imparting partial protection against E. maxima challenge in chickens and it could be an effective antigen candidate for the development of new vaccines against E. maxima.

Association Between In Vitro Susceptibility to Natamycin and Voriconazole and Clinical Outcomes in Fungal Keratitis

PubMed Central

Sun, Catherine Q.; Lalitha, Prajna; Prajna, N. Venkatesh; Karpagam, Rajarathinam; Geetha, Manoharan; O’Brien, Kieran S.; Oldenburg, Catherine E.; Ray, Kathryn J.; McLeod, Stephen D.; Acharya, Nisha R.; Lietman, Thomas M.

2014-01-01

Purpose To assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial. Design Experimental study using data from a randomized comparative trial. Participants Of the 323 patients enrolled in the trial, we were able to obtain MIC values from 221 patients with monocular fungal keratitis. Methods The Mycotic Ulcer Treatment Trial I (MUTT I) was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines. The relationship between MIC and clinical outcome was assessed. Main Outcome Measures The primary outcome was 3-month best spectacle-corrected visual acuity. Secondary outcomes included 3-month infiltrate/scar size, corneal perforation and/or therapeutic penetrating keratoplasty (TPK), and time to re-epithelialization. Results A 2-fold increase in MIC was associated with a larger 3-month infiltrate/scar size (0.21 mm, 95% confidence interval [CI] 0.10–0.31, P <0.001) and increased odds of perforation (odds ratio [OR] 1.32, 95% CI 1.04–1.69, P=0.02). No correlation was found between MIC and 3-month visual acuity. For natamycin-treated cases, an association was found between higher natamycin MIC with larger 3-month infiltrate/scar size (0.29 mm, 95% CI 0.15–0.43, P<0.001) and increased perforations (OR 2.41, 95% CI 1.46–3.97, P<0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study. Conclusion Decreased susceptibility to natamycin was associated with increased infiltrate/scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome. PMID:24746358

Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis.

PubMed

Sun, Catherine Q; Lalitha, Prajna; Prajna, N Venkatesh; Karpagam, Rajarathinam; Geetha, Manoharan; O'Brien, Kieran S; Oldenburg, Catherine E; Ray, Kathryn J; McLeod, Stephen D; Acharya, Nisha R; Lietman, Thomas M

2014-08-01

To assess the association between minimum inhibitory concentration (MIC) and clinical outcomes in a fungal keratitis clinical trial. Experimental study using data from a randomized comparative trial. Of the 323 patients enrolled in the trial, we were able to obtain MIC values from 221 patients with monocular fungal keratitis. The Mycotic Ulcer Treatment Trial I was a randomized, double-masked clinical trial comparing clinical outcomes of monotherapy with topical natamycin versus voriconazole for the treatment of fungal keratitis. Speciation and determination of MIC to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute guidelines. The relationship between MIC and clinical outcome was assessed. The primary outcome was 3-month best spectacle-corrected visual acuity. Secondary outcomes included 3-month infiltrate or scar size; corneal perforation and/or therapeutic penetrating keratoplasty; and time to re-epithelialization. A 2-fold increase in MIC was associated with a larger 3-month infiltrate or scar size (0.21 mm; 95% confidence interval [CI], 0.10-0.31; P < 0.001) and increased odds of perforation (odds ratio, 1.32; 95% CI, 1.04-1.69; P = 0.02). No correlation was found between MIC and 3-month visual acuity. For natamycin-treated cases, an association was found between higher natamycin MIC with larger 3-month infiltrate or scar size (0.29 mm; 95% CI, 0.15-0.43; P < 0.001) and increased perforations (odds ratio, 2.41; 95% CI, 1.46-3.97; P < 0.001). Among voriconazole-treated cases, the voriconazole MIC did not correlate with any of the measured outcomes in the study. Decreased susceptibility to natamycin was associated with increased infiltrate or scar size and increased odds of perforation. There was no association between susceptibility to voriconazole and outcome. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Inhibitory and bactericidal activities of levofloxacin, ofloxacin, erythromycin, and rifampin used singly and in combination against Legionella pneumophila.

PubMed Central

Baltch, A L; Smith, R P; Ritz, W

1995-01-01

The susceptibilities of 56 Legionella pneumophila isolates (43 clinical and 15 environmental isolates) to levofloxacin, ofloxacin, erythromycin, and rifampin were studied with buffered charcoal yeast extract (BCYE) agar (inoculum, 10(4) CFU per spot), and the susceptibilities of five isolates were studied with buffered yeast extract (BYE) broth (inoculum, 10(5) CFU/ml). The MICs inhibiting 90% of strains tested on BCYE agar were 0.125, 0.25, 1.0, and < or = 0.004 micrograms/ml for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MICs by the BYE broth dilution method were 1 to 3, 2, 1 to 2, and 1 tube lower than those by the agar dilution method for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MBCs were 1 to 2 tubes higher than the broth dilution MICs for levofloxacin, 1 to 3 tubes higher than the broth dilution MICs for ofloxacin, 1 to 3 tubes higher than the broth dilution MICs for erythromycin, and the same as the broth dilution MICs for rifampin. In kinetic time-kill curve studies, at drug concentrations of 1.0 and 2.0 times the MIC, the most active drugs were levofloxacin and rifampin. At 72 h, concentrations of levofloxacin and rifampin of 2.0 times the MIC demonstrated a bactericidal effect against L. pneumophila. In contrast, at concentrations of 1.0 and 2.0 times the MICs regrowth was observed with ofloxacin and only a gradual decrease in the numbers of CFU per milliliter was observed with erythromycin. Only a minor inhibitory effect was observed with 0.25 or 0.5 time the MICs of all drugs at 24 to 48 h, with regrowth occurring at 72 h. In contrast to erythromycin or ofloxacin plus rifampin at 0.25 time the MICs, only levofloxacin plus rifampin demonstrated synergy. Thus, levofloxacin demonstrated the best inhibitory and bactericidal effects against L. pneumophila when it was studied alone or in a combination with rifampin. PMID:7486896

Pharmacokinetic-pharmacodynamic integration and modelling of oxytetracycline administered alone and in combination with carprofen in calves.

PubMed

Brentnall, C; Cheng, Z; McKellar, Q A; Lees, P

2013-06-01

The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oxytetracycline were investigated, when administered both alone and in the presence of carprofen, in healthy calves. The study comprised a four treatment, four sequences, and four period cross-over design and used a tissue cage model, which permitted the collection of serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). There were no clinically relevant differences in the PK profile of oxytetracycline when administered alone and when administered with carprofen. PK-PD integration was undertaken for a pathogenic strain of Mannheimia haemolytic (A1 76/1), by correlating in vitro minimum inhibitory concentration (MIC) and time-kill data with in vivo PK data obtained in the cross-over study. Based on in vitro susceptibility in cation adjusted Mueller Hinton Broth (CAMHB) and in vivo determined PK variables, ratios of maximum concentration (Cmax) and area under curve (AUC) to MIC and time for which concentration exceeded MIC (T>MIC) were determined. The CAMHB MIC data satisfied integrated PK/PD relationships predicted to achieve efficacy for approximately 48 h after dosing; mean values for serum were 5.13 (Cmax/MIC), 49.3 h (T>MIC) and 126.6 h (AUC(96h)/MIC). Similar findings were obtained when oxytetracycline was administered in the presence of carprofen, with PK-PD indices based on MIC determined in CAMHB. However, PK-PD integration of data, based on oxytetracycline MICs determined in the biological fluids, serum, exudate and transudate, suggest that it possesses, at most, limited direct killing activity against the M. haemolytica strain A1 76/1; mean values for serum were 0.277 (Cmax/MIC), 0 h (T>MIC) and 6.84 h (AUC(96h)/MIC). The data suggest that the beneficial therapeutic effects of oxytetracycline may depend, at least in part, on actions other than direct inhibition of bacterial growth. Copyright © 2013 Elsevier Ltd. All rights reserved.

In vitro bactericidal activity of aminoglycosides, including the next-generation drug plazomicin, against Brucella spp.

USDA-ARS?s Scientific Manuscript database

Plazomicin is a next-generation aminoglycoside with a potentially improved safety profile compared to other aminoglycosides. This study assessed plazomicin MICs and MBCs in four Brucella spp. reference strains. Like other aminoglycosides and aminocyclitols, plazomicin MBC values equaled MIC values ...

Reevaluation of interpretive criteria for Haemophilus influenzae by using meropenem (10-microgram), imipenem (10-microgram), and ampicillin (2- and 10-microgram) disks.

PubMed Central

Zerva, L; Biedenbach, D J; Jones, R N

1996-01-01

A collection of 300 Haemophilus influenzae clinical strains was used to assess in vitro susceptibility to carbapenems (meropenem, imipenem) by MIC and disk diffusion methods and to compare disk diffusion test results with two potencies of ampicillin disks (2 and 10 micrograms). The isolates included ampicillin-susceptible or- intermediate (167 strains), beta-lactamase-positive (117 strains), and beta-lactamase-negative ampicillin-resistant (BLNAR; 16 strains) organisms. Disk diffusion testing was performed with 10-micrograms meropenem disks from two manufacturers. Meropenem was highly active against H. influenzae strains (MIC50, 0.06 microgram/ml; MIC90, 0.25 microgram/ml; MIC50 and MIC90, MICs at which 50 and 90%, respectively, of strains are inhibited) and was 8- to 16-fold more potent than imipenem (MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml). Five non-imipenem-susceptible strains were identified (MIC, 8 micrograms/ml), but the disk diffusion test indicated susceptibility (zone diameters, 18 to 21 mm). MIC values of meropenem, doxycycline, ceftazidime, and ceftriaxone for BLNAR strains were two- to fourfold greater than those for other strains. The performance of both meropenem disks was comparable and considered acceptable. A single susceptible interpretive zone diameter of > or = 17 mm (MIC, < = or 4 micrograms/ml) was proposed for meropenem. Testing with the 2-micrograms ampicillin disk was preferred because of an excellent correlation between MIC values and zone diameters (r = 0.94) and superior interpretive accuracy with the susceptible criteria at > or = 17 mm (MIC, < or = 1 microgram/ml) and the resistant criteria at < or = 13 mm (MIC, > or = 4 micrograms/ml). Among the BLNAR strains tested, 81.3% were miscategorized as susceptible or intermediate when the 10-micrograms ampicillin disk was used, while the 2-micrograms disk produced only minor interpretive errors (12.5%). Use of these criteria for testing H. influenzae against meropenem and ampicillin should maximize reference test and standardized disk diffusion test performance with the Haemophilus Test Medium. The imipenem disk diffusion test appears compromised and should be used with caution for detecting strains for which imipenem MICs are elevated. PMID:8818892

Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens

PubMed

Scalon Cunha, Luis C; Andrade e Silva, Márcio L; Cardoso Furtado, Niege A J; Vinhólis, Adriana H C; Martins, Carlos H; da Silva Filho, Ademar A; Cunha, Wilson R

2007-01-01

Triterpene acids (ursolic, oleanoic, gypsogenic, and sumaresinolic acids) isolated from Miconia species, along with a mixture of ursolic and oleanolic acids and a mixture of maslinic and 2-a-hydroxyursolic acids, as well as ursolic acid derivatives were evaluated against the following microorganisms: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis, which are potentially responsible for the formation of dental caries in humans. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) during the evaluation of the antibacterial activity. All the isolated compounds, mixtures, and semi-synthetic derivatives displayed activity against all the tested bacteria, showing that they are promising antiplaque and anticaries agents. Ursolic and oleanolic acids displayed the most intense antibacterial effect, with MIC values ranging from 30 microg/mL to 80 microg/mL. The MIC values of ursolic acid derivatives, as well as those obtained for the mixture of ursolic and oleanolic acids showed that these compounds do not have higher antibacterial activity when compared with the activity observed with either ursolic acid or oleanolic acid alone. With regard to the structure-activity relationship of triterpene acids and derivatives, it is suggested that both hydroxy and carboxy groups present in the triterpenes are important for their antibacterial activity against oral pathogens.

Growth Inhibition and Morphological Alterations of Trichophyton Rubrum Induced by Essential oil from Cymbopogon Winterianus Jowitt Ex Bor

PubMed Central

de Oliveira Pereira, Fillipe; Alves Wanderley, Paulo; Cavalcanti Viana, Fernando Antônio; Baltazar de Lima, Rita; Barbosa de Sousa, Frederico; de Oliveira Lima, Edeltrudes

2011-01-01

Trichophyton rubrum is one of the most common fungi causer of dermatophytosis, mycosis that affect humans and animals around the world. Researches aiming new products with antifungal activity become necessary to overcome difficulties on treatment of these infections. Accordingly, this study aimed to investigate the antifungal activity of essential oil from Cymbopogon winterianus against the dermatophyte T. rubrum. The antifungal screening was performed by solid medium diffusion method with 16 T. rubrum strains, minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined using the microdilution method. The effects on mycelial dry weight and morphology were also observed. Screening showed essential oil in natura inhibited all the tested strains, with inhibition zones between 24-28 mm diameter. MIC50 and MIC90 values of the essential oil were 312 μg/mL for nearly all the essayed strains (93.75 %) while the MFC50 and MFC90 values were about eight times higher than MIC for all tested strains. All tested essential oil concentrations managed to inhibit strongly the mycelium development. Main morphological changes on the fungal strains observed under light microscopy, which were provided by the essential oil include loss of conidiation, alterations concerning form and pigmentation of hyphae. In the oil presence, colonies showed folds, cream color and slightly darker than the control, pigment production was absent on the reverse and with evident folds. It is concluded that C. winterianus essential oil showed activity against T. rubrum. Therefore, it could be known as potential antifungal compound especially for protection against dermatophytosis. PMID:24031626

[Molecular epidemiology and antifungal susceptibility of Candida species isolated from urine samples of patients in intensive care unit].

PubMed

Yüksekkaya, Serife; Fındık, Duygu; Arslan, Uğur

2011-01-01

The aims of this study were to analyse the amphotericin B and fluconazole susceptibility and molecular epidemiology of Candida strains (Candida albicans, Candida tropicalis and Candida glabrata) isolated from the urine samples of patients hospitalized in the intensive care unit. Identification of the isolates was done according to microscopic morphology (chlamydospor, blastospor, pseudohyphae and true hyphae) on cornmeal agar, germ tube formation and carbohydrate assimilation patterns (API ID 32C bioMérieux, France). Antifungal susceptibilities of the isolates were determined by in vitro broth microdilution method recommended by Clinical and Laboratory Standards Institute (CLSI). To investigate the clonal relationship of the isolates, randomly amplified polymorphic DNA (RAPD) analysis was performed by using Cnd3 primer. Of the 56 Candida isolates minimum inhibitory concentration (MIC) ranges, MIC50 and MIC90 values for amphotericin B were 0.125-1 µg/ml, 0.125 and 0.5 µg/ml for C.albicans, 0.125-1 µg/ml, 0.25 and 1 µg/ml for C.tropicalis and 0.125-1 µg/ml, 0.25 and 1 µg/ml for C.glabrata, respectively. Fluconazole MIC ranges, MIC50 and MIC90 values were 0.25-4 µg/ml, 0.25 and 0.5 µg/ml for C.albicans, 0.25-16 µg/ml, 0.5 and 1 µg/ml for C.tropicalis and 0.5-64 µg/ml, 8 and 16 µg/ml for C.glabrata, respectively. For amphotericin B, none of the isolates had high MIC values (MIC > 1 µg/ml). While one of the C.glabrata isolates was resistant to fluconazole (MIC ≥ 64 µg/ml), one C.tropicalis and two C.glabrata isolates were dose-dependent susceptible (MIC: 16-32 µg/ml). The results of RAPD analysis indicated an exogenous spread from two clones for C.albicans, one clone for C.glabrata and one clone for C.tropicalis. This study underlines the importance of molecular epidemiological analysis of clinical samples together with hospital environmental samples in terms of Candida spp. To determine the exogenous origin for the related strains and to prevent nosocomial Candida infections.

Activity of nadifloxacin (OPC-7251) and seven other antimicrobial agents against aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin infections.

PubMed

Nenoff, P; Haustein, U-F; Hittel, N

2004-10-01

The in vitro activity of nadifloxacin (OPC-7251), a novel topical fluoroquinolone, was assessed and compared with those of ofloxacin, oxacillin, flucloxacillin, cefotiam, erythromycin, clindamycin, and gentamicin against 144 Gram-positive bacteria: 28 Staphylococcus aureus, 10 Streptococcus spp., 68 coagulase-negative staphylococci (CNS), 36 Propionibacterium acnes, and 2 Propionibacterium granulosum strains. All strains originated from bacterial-infected skin disease and were isolated from patients with impetigo, secondary infected wounds, folliculitis and sycosis vulgaris, and impetiginized dermatitis. In vitro susceptibility of all clinical isolates was tested by agar dilution procedure and minimum inhibitory concentrations (MICs) were determined. Nadifloxacin was active against all aerobic and anaerobic isolates. MIC(90) (MIC at which 90% of the isolates are inhibited) was 0.1 microg/ml for S. aureus, 0.78 microg/ml for both Streptococcus spp. and CNS, and 0.39 microg/ml for Propionibacterium spp. On the other hand, resistant strains with MICs exceeding 12.5 mug/ml were found in tests with the other antibiotics. For both CNS and Propionibacterium acnes, MIC(90) values > or =100 microg/ml were demonstrated for erythromycin. Ofloxacin, cefotiam, erythromycin, clindamycin and gentamicin exhibited MIC(90) values < or =1 microg/ml for some bacterial species tested. Both oxacillin and flucloxacillin were active against all investigated bacterial species with MIC(90) values < or =1 microg/ml. In summary, nadifloxacin, a topical fluoroquinolone, was found to be highly active against aerobic and anaerobic bacteria isolated from patients with infected skin disease, and seems to be a new alternative for topical antibiotic treatment in bacterial skin infections.

Comparative in vitro activity of carbapenems against major Gram-negative pathogens: results of Asia-Pacific surveillance from the COMPACT II study.

PubMed

Kiratisin, Pattarachai; Chongthaleong, Anan; Tan, Thean Yen; Lagamayo, Evelina; Roberts, Sally; Garcia, Jemelyn; Davies, Todd

2012-04-01

Resistance rates amongst Gram-negative pathogens are increasing in the Asia-Pacific region. The Comparative Activity of Carbapenem Testing (COMPACT) II study surveyed the carbapenem susceptibility and minimum inhibitory concentrations (MICs) of doripenem, imipenem and meropenem against 1260 major Gram-negative pathogens isolated from hospitalised patients at 20 centres in five Asia-Pacific countries (New Zealand, the Philippines, Singapore, Thailand and Vietnam) during 2010. Pseudomonas aeruginosa (n=625), Enterobacteriaceae (n=500), and other Gram-negative pathogens including Acinetobacter baumannii (n=135) were collected from patients with bloodstream infection (32.2%), nosocomial pneumonia including ventilator-associated pneumonia (58.1%), and complicated intra-abdominal infection (9.7%), with 36.7% being isolated from patients in an Intensive Care Unit. As high as 29.8% of P. aeruginosa and 73.0% of A. baumannii isolates were not susceptible to at least a carbapenem, whereas the majority of Enterobacteriaceae (97.2%) were susceptible to all carbapenems. Respective MIC(50)/MIC(90) values (MICs for 50% and 90% of the organisms, respectively) of doripenem, imipenem and meropenem were: 0.38/8, 1.5/32 and 0.38/16 mg/L for P. aeruginosa; 0.023/0.094, 0.25/0.5 and 0.032/0.094 mg/L for Enterobacteriaceae; and 32/64, 32/128 and 32/64 mg/L for A. baumannii. Doripenem and meropenem had comparable activity against P. aeruginosa, both being more active than imipenem. All carbapenems were highly potent against Enterobacteriaceae, although imipenem demonstrated higher MIC values than doripenem and meropenem. The three carbapenems showed less activity against A. baumannii. The high prevalence of carbapenem resistance amongst important nosocomial pathogens (P. aeruginosa and A. baumannii) warrants rigorous infection control measures and appropriate antimicrobial use in the Asia-Pacific region. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

In vitro activity of two amphotericin B formulations against Malassezia furfur strains recovered from patients with bloodstream infections.

PubMed

Iatta, Roberta; Immediato, Davide; Montagna, Maria Teresa; Otranto, Domenico; Cafarchia, Claudia

2015-04-01

Although guidelines for the treatment of Malassezia furfur fungemia are not yet defined, clinical data suggest that amphotericin B (AmB) is effective for treating systemic infections. In the absence of clinical breakpoints for Malassezia yeasts, epidemiological cut-off values (ECVs) are useful to discriminate between isolates with and without drug resistance. This study aimed to compare the distribution of minimal inhibitory concentration (MIC) and the ECVs for AmB of both deoxycholate (d-AmB) and liposomal (l-AmB) formulations of M. furfur isolates. The 84 M. furfur strains analyzed, which included 56 from blood, sterile sites and catheters, and 28 from skin, were isolated from patients with bloodstream infections. MICs were determined by the modified broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). The l-AmB MIC and the ECVs were two-fold lower than those of d-AmB and a lower l-AmB mean MIC value was found for blood isolates than from skin. The ECVs for l-AmB and d-AmB were 8 mg/l and 32 mg/l, respectively. Three strains (3.6%) showed l-AmB MIC higher than ECV (MIC > 8 mg/l) of which two were isolated from the catheter tip of patients treated with micafugin, l-Amb and fluconazole, and one from skin. The results showed that the l-AmB might be employed for assessing the in vitro antifungal susceptibility of M. furfur by a modified CLSI protocol and that ECVs might be useful for detecting the emergence of resistance. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Activity of Delafloxacin When Tested Against Bacterial Surveillance Isolates Collected in the US and Europe During 2014–2016 as Part of a Global Surveillance Program

PubMed Central

Flamm, Robert K; Shortridge, Dee; Huband, Michael D; McCurdy, Sandra; Pfaller, Michael A

2017-01-01

Abstract Background Delafloxacin (DLX) is an investigational anionic fluoroquinolone with an NDA that is under US FDA review to treat acute bacterial skin and skin structure infections and is undergoing Phase 3 studies to treat community-acquired bacterial pneumonia. Methods A total of 36,683 Gram-positive (GP) and -negative (GN) bacteria isolated during 2014–2016 were selected from medical centers in the US and Europe. Susceptibility testing (S) was performed by frozen-form broth microdilution methods for DLX and comparators. Results DLX was very active against Staphylococcus aureus (SA, n = 9,355; MIC50/90, 0.008/0.5 mg/L) while the levofloxacin (LEV) MIC50/90 was 0.25/>4 mg/L (67.9%S). The MIC50/90 for methicillin-resistant SA (MRSA) was 0.12/1 mg/L. For MRSA, all isolates were S to vancomycin and daptomycin (DAP), linezolid and tigecycline (TGC) S was ≥99.9%. Decreased rates of S were noted for LEV (29.8%), clindamycin (72.9%), and erythromycin (17.3/17.8%; CLSI/EUCAST). Minocycline (MIC50/90, 0.12/0.25 mg/L), ceftaroline (MIC50/90, 0.25/0.5 mg/L), DAP (MIC50/90, 0.5/0.5 mg/L), and DLX (MIC50/90, 0.015/0.5 mg/L) were the most active agents tested against coagulase-negative staphylococci. Against Streptococcus pneumoniae (SPN), the MIC50/90 for DLX (0.015/0.03 mg/L) and TGC (0.03/0.06 mg/L) were the lowest among the agents tested. The DLX MIC50/90 values did not vary among the penicillin-S, -intermediate, and -R subgroups of SPN. The MIC50/90 values for DLX against S. pyogenes and S. agalactiae were 0.015/0.03 mg/L. DLX was highly active against Haemophilus influenzae. The DLX MIC50/90 (≤0.001/0.004 mg/L) was the same for β-lactamase positive and negative H. influenzae. Against Enterobacteriaceae, 76.0% of DLX MIC values were ≤1 mg/L. Susceptibility to LEV was 80.8%, and S to ceftriaxone, ceftazidime (CAZ), and cefepime ranged from 78.5–86.3%. A total of 72.6% of Pseudomonas aeruginosa isolates exhibited DLX MIC values ≤1 mg/L, while LEV S was 73.2% and CAZ was 81.6%. The MIC50/90 for both DLX and LEV were 0.5/>4 mg/L, respectively. Conclusion DLX was active against a broad range of GP and GN bacteria, including MRSA and multidrug-resistant SPN. DLX merits further study as therapy in infections in which these organisms may occur. Disclosures R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant S. McCurdy, Melinta Therapeutics: Employee, Salary M. A. Pfaller, Melinta Therapeutics: Research Contractor, Research grant

Automated reading of MIC microdilution trays containing fluorogenic enzyme substrates with the Sensititre Autoreader.

PubMed Central

Staneck, J L; Allen, S D; Harris, E E; Tilton, R C

1985-01-01

The Sensititre Autoreader is a microcomputer-driven instrument capable of automatically reading antimicrobial susceptibility microdilution trays. The instrument measures the fluorescence liberated by bacterial enzymatic activity on fluorogenic substrates as an indicator of growth in each well. A mathematical algorithm converts the fluorescent signals from an antimicrobial dilution series to an MIC endpoint. A three-center study evaluated the performance of the Autoreader in comparison with MIC determined visually in a duplicate set of control plates lacking fluorogenic substrate. Among 828 isolates of gram-negative bacilli tested against 17 antimicrobial agents, Autoreader 18-h MIC were within +/- 1 twofold dilution of control MIC values (agreement) in 95.3% of instances. In 3.5% of the instances, Autoreader values occurred +/- 2 half-step dilutions from control values (minor discrepancy), and in only 1.2% of instances did Autoreader values deviate from control values by greater than +/- 2 dilution steps (major discrepancy). Agreement, minor discrepancies, and major discrepancies were noted among 148 gram-positive cocci tested against 11 antimicrobial agents in 93.5, 4.8, and 1.7% of the instances, respectively. Over half of the major discrepancies noted with gram-negative bacilli occurred with Proteus mirabilis-beta-lactam combinations, a problem that was resolved when a lower initial inoculum was used. Inter-and intralaboratory reproducibility was excellent. Standard Sensititre susceptibility trays may be instrument read at 18 h reproducibly and accurately with only slight modification of conventional procedures to include fluorogenic enzyme substrates in the incubation broth. PMID:4031033

Isolation and identification of antibacterial compounds from Thymus kotschyanus aerial parts and Dianthus caryophyllus flower buds.

PubMed

Mohammed, Muthanna J; Al-Bayati, Firas A

2009-06-01

The aerial parts of Thymus kotschyanus Boiss. and Hohen. (Lamiaceae) and flower buds of Dianthus caryophyllus L. (Caryophyllaceae) have been traditionally implemented in the treatment of wounds, throat and gum infections and gastro-intestinal disorder by the indigenous people of northern Iraq, although the compounds responsible for the medicinal properties have not been identified. In this study, antibacterial compounds from both plants were isolated and characterized, and the biological activity of each compound was assessed individually and combined. Compounds were isolated and characterized from the extracted essential oils of both plants using different spectral techniques: TLC, FTIR spectra and HPLC. The minimum inhibitory concentrations MIC values for the compounds were assessed individually and combined based on a microdilution and the checkerboard method in 96 multi-well microtiter plates. Two known compounds were isolated from the essential oils of both plants and were identified as thymol and eugenol. The isolated compounds were investigated for their single and combined antibacterial activities against seven selected pathogenic bacteria; Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Proteus mirabilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Thymol MIC values ranged from 15.6 to 250.0 microg/ml and B. cereus was found to be the most sensitive pathogen with a MIC value of 15.6 microg/ml. Eugenol achieved stronger MIC values against most tested pathogens and the best MIC value (15.6 microg/ml) was observed against B. cereus, L. monocytogenes and K. pneumoniae whereas, S. aureus, P. mirabilis and E. coli were inhibited with a MIC value of 31.2 microg/ml. Combination results had antibacterial enhancement against most pathogens and the best synergistic result was seen against P. mirabilis and E. coli. The isolation of two antibacterial compounds from Thymus kotschyanus aerial parts and Dianthus caryophyllus flower buds validates the use of these species in the treatment of throat and gum infections, wound-healing and gastro-intestinal disorder.

Susceptibility patterns for amoxicillin/clavulanate tests mimicking the licensed formulations and pharmacokinetic relationships: do the MIC obtained with 2:1 ratio testing accurately reflect activity against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis?

PubMed

Pottumarthy, Sudha; Sader, Helio S; Fritsche, Thomas R; Jones, Ronald N

2005-11-01

Amoxicillin/clavulanate has recently undergone formulation changes (XR and ES-600) that represent 14:1 and 16:1 ratios of amoxicillin/clavulanate. These ratios greatly differ from the 2:1 ratio used in initial formulations and in vitro susceptibility testing. The objective of this study was to determine if the reference method using a 2:1 ratio accurately reflects the susceptibility to the various clinically used amoxicillin/clavulanate formulations and their respective serum concentration ratios. A collection of 330 Haemophilus influenzae strains (300 beta-lactamase-positive and 30 beta-lactamase-negative) and 40 Moraxella catarrhalis strains (30 beta-lactamase-positive and 10 beta-lactamase-negative) were tested by the broth microdilution method against eight amoxicillin/clavulanate combinations (4:1, 5:1, 7:1, 9:1, 14:1, and 16:1 ratios; 0.5 and 2 microg/mL fixed clavulanate concentrations) and the minimum inhibitory concentration (MIC) results were compared with those obtained with the reference 2:1 ratio testing. For the beta-lactamase-negative strains of both genera, there was no demonstrable change in the MIC values obtained for all ratios analyzed (2:1 to 16:1). For the beta-lactamase-positive strains of H. influenzae and M. catarrhalis, at ratios >or=4:1 there was a shift in the central tendency of the MIC scatterplot compared with the results of testing 2:1 ratio. As a result, there was a 2-fold dilution increase in the MIC(50) and MIC(90) values, most evident for H. influenzae and BRO-1-producing M. catarrhalis strains. For beta-lactamase-positive strains of H. influenzae, the shift resulted in a change in the interpretive result for 3 isolates (1.0%) from susceptible using the reference method (2:1 ratio) to resistant (8/4 microg/mL; very major error) at the 16:1 ratio. In addition, the number of isolates with MIC values at or 1 dilution lower than the breakpoint (4/2 microg/mL) increased from 5% at 2:1 ratio to 32-33% for ratios 14:1 and 16:1. Our results indicate that, for the beta-lactamase-positive strains of H. influenzae and M. catarrhalis, the results of the amoxicillin/clavulanate reference 2:1 ratio testing do not accurately represent all the currently licensed formulations. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment might be compromised when higher amoxicillin/clavulanate ratios are used clinically. With a better understanding of PK/PD parameters, reevaluation of the amoxicillin/clavulanate in vitro susceptibility testing should be considered by the standardizing authorities to reflect the licensed formulations and accurately predict clinical outcomes.

Essential oils against foodborne pathogens and spoilage bacteria in minced meat.

PubMed

Barbosa, Lidiane Nunes; Rall, Vera Lucia Mores; Fernandes, Ana Angélica Henrique; Ushimaru, Priscila Ikeda; da Silva Probst, Isabella; Fernandes, Ary

2009-01-01

The antimicrobial activity of essential oils of oregano, thyme, basil, marjoram, lemongrass, ginger, and clove was investigated in vitro by agar dilution method and minimal inhibitory concentration (MIC) determination against Gram-positive (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative strains (Escherichia coli and Salmonella Enteritidis). MIC(90%) values were tested against bacterial strains inoculated experimentally in irradiated minced meat and against natural microbiota (aerobic or facultative, mesophilic, and psychrotrophic bacteria) found in minced meat samples. MIC(90%) values ranged from 0.05%v/v (lemongrass oil) to 0.46%v/v (marjoram oil) to Gram-positive bacteria and from 0.10%v/v (clove oil) to 0.56%v/v (ginger oil) to Gram-negative strains. However, the MIC(90%) assessed on minced meat inoculated experimentally with foodborne pathogen strains and against natural microbiota of meat did not show the same effectiveness, and 1.3 and 1.0 were the highest log CFU/g reduction values obtained against tested microorganisms.

Essential Oils Against Foodborne Pathogens and Spoilage Bacteria in Minced Meat

PubMed Central

Barbosa, Lidiane Nunes; Rall, Vera Lucia Mores; Fernandes, Ana Angélica Henrique; Ushimaru, Priscila Ikeda; da Silva Probst, Isabella

2009-01-01

Abstract The antimicrobial activity of essential oils of oregano, thyme, basil, marjoram, lemongrass, ginger, and clove was investigated in vitro by agar dilution method and minimal inhibitory concentration (MIC) determination against Gram-positive (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative strains (Escherichia coli and Salmonella Enteritidis). MIC90% values were tested against bacterial strains inoculated experimentally in irradiated minced meat and against natural microbiota (aerobic or facultative, mesophilic, and psychrotrophic bacteria) found in minced meat samples. MIC90% values ranged from 0.05%v/v (lemongrass oil) to 0.46%v/v (marjoram oil) to Gram-positive bacteria and from 0.10%v/v (clove oil) to 0.56%v/v (ginger oil) to Gram-negative strains. However, the MIC90% assessed on minced meat inoculated experimentally with foodborne pathogen strains and against natural microbiota of meat did not show the same effectiveness, and 1.3 and 1.0 were the highest log CFU/g reduction values obtained against tested microorganisms. PMID:19580445

[Bacteriological and clinical studies on flomoxef in the pediatric field].

PubMed

Sunakawa, K; Ishizuka, Y; Kawai, N; Saito, N; Iwata, S; Sato, Y; Akita, H; Kusano, S; Aoki, T

1987-08-01

Bacteriological and clinical studies on flomoxef (FMOX, 6315-S) were performed and the results obtained are summarized below. 1. The MIC values of FMOX against 307 clinically isolated strains of Staphylococcus aureus were 0.024 to 100 micrograms/ml with a peak MIC of 0.39 microgram/ml, and the MIC90 value was 1.56 micrograms/ml. The MIC90 against methicillin resistant S. aureus (MRSA) was 25 micrograms/ml. 2. FMOX was administered to 15 children with pediatric bacterial infections, and the effectiveness was rated excellent or good in all cases. 3. In bacteriological evaluation, 7 of 11 strains identified prior to the treatment were eliminated (63.6%). 4. As side effects, diarrhea or soft stool was found in 3 cases and eruption in 1 case. As abnormal laboratory values, eosinophilia and thrombocytosis were found in 1 case each. 5. On the intestinal bacterial flora, FMOX had a marked influence just as did other Group 4 and 5 cephems antibiotics. 6. FMOX interfered little with the coagulation system or platelet aggregation.

Corneal Optical Quality Following Sub 1.8 mm Micro-Incision Cataract Surgery vs. 2.2 mm Mini-Incision Coaxial Phacoemulsification

PubMed Central

Alió, Jorge L.; Elkady, Bassam; Ortiz, Dolores

2010-01-01

Purpose: To study and compare the effects of the micro-incision cataract surgery (MICS-sub 1.8 mm) and miniincision coaxial phacoemulsification (2.2 mm) on the optical quality of the cornea characterized in terms of corneal aberrations. Materials and Methods: Fifty eyes underwent MICS and 50 mini-incision phacoemulsification, by the same surgeon. Both types of cataract surgery were performed using low ultrasound power and through a clear corneal incision, placed on the steepest corneal meridian ranging from 1.6 to 1.8 in MICS (Group I) and from 2.12 to 2.3 mm in mini-incision coaxial phacoemulsification (Group II). Seidel and Zernike aberration coefficients and RMS values were obtained for a 6-mm pupil preoperatively and one month after surgery. Results: The corneal astigmatism did not show statistically significant changes in either of the two groups: (MICS: –0.73 ± 0.63, –0.65 ± 0.53 D, P = 0.25), (mini-incision phacoemulsification; –1.21 ± 1.52, –1.00 ± 1.19 D, P = 0.12). The total RMS remained unchanged after MICS (1.77 ± 1.7, 1.65 ± 1.3 μm, P = 0.18) and mini-incision phacoemulsification (2.00 ± 1.87, 2.09 ± 1.8 μm, P = 0.41). Statistically significant changes were found for coma (P = 0.004) and higher-order aberrations (P < 0.001), showing MICS significantly less changes in cornea. Conclusions: Both MICS and mini-incision phacoemulsification do not degrade the optical quality of the cornea. Both surgeries do not induce a modification of the corneal astigmatism, even in the axis. It seems that 2 mm is the limit around which no optical changes are induced by cataract surgery in the human cornea. PMID:20543945

In vitro antibacterial and antifungal activities of Rhus tripartitum used as antidiarrhoeal in Tunisian folk medicine.

PubMed

Abbassi, Feten; Hani, Khaled

2012-01-01

Rhus tripartitum (African sumac) is a plant commonly used in Tunisian traditional medicine to treat diarrhoea and dysentery. In this study, we have demonstrated that R. tripartitum extracts exhibited a significant broad spectrum activity against one or more of the test microorganisms with a zone size ranging from 8 to 28 mm in diameter. These diameters are much higher than those obtained with standard antibiotics. The chloroformic extracts were found to be effective against bacterial and fungal strains tested, with MIC values ranging between 0.07 and 0.62 mg mL(-1) against Staphylococcus aureus and Candida albicans. However, ethyl-acetate/methanol fractions showed a selective activity only against bacterial microorganisms with low MIC values between 0.07 and 0.15 mg mL(-1). The overall results suggested that the traditional use of R. tripartitum for the treatment of diarrhoea tract infections was attributed to the presence of antibacterial agents.

Antimicrobial susceptibility of porcine Brachyspira hyodysenteriae and Brachyspira pilosicoli isolated in Sweden between 1990 and 2010.

PubMed

Pringle, Märit; Landén, Annica; Unnerstad, Helle Ericsson; Molander, Benedicta; Bengtsson, Björn

2012-09-21

The anaerobic spirochetes Brachyspira hyodysenteriae and Brachyspira pilosicoli cause diarrheal diseases in pigs. Their fastidious nature has hampered standardization of methods for antimicrobial susceptibility testing. For monitoring of antimicrobial susceptibility wild type cutoff values are needed to define where the wild type distribution of MICs ends and no approved cutoffs are available for Brachyspira spp. In this study antimicrobial susceptibility data for both species (in total 906 isolates) were compiled and analyzed and wild type cut off values for B. hyodysenteriae proposed. The MICs of tiamulin, valnemulin, tylosin, tylvalosin, doxycycline and lincomycin were determined by broth dilution in brain heart infusion broth supplemented with 10% fetal calf serum. The compiled MICs from the broth dilution tests of the B. hyodysenteriae type strain, B78T (ATCC® 27164T), showed that the method yields reproducible results. In an international perspective the frequencies of isolates with decreased antimicrobial susceptibility were low among both B. hyodysenteriae and B. pilosicoli. However, in B. pilosicoli a constant level of 10-15% isolates with tiamulin MICs >4 μg/ml was detected between 2002 and 2010 and in B. hyodysenteriae a gradual increase in tiamulin MICs was seen between 1990 and 2003 although this increase has ceased during the last years. The wild type cutoff values proposed for B. hyodysenteriae are: tiamulin >0.25 μg/ml, valnemulin >0.125 μg/ml, tylosin >16 μg/ml, tylvalosin >1 μg/ml, lincomycin >1 μg/ml and doxycycline >0.5 μg/ml. The broth dilution method used in this study has over the years generated tightly grouped MIC populations for the field isolates and reproducible results for the control strain B78T and is therefore a suitable antimicrobial susceptibility test method for monitoring of Brachyspira spp. Here we propose wild type cutoff values for six antimicrobial agents for B. hyodysenteriae tested by broth dilution based on MIC distributions and the current knowledge on mechanisms of resistance in this species. There are few studies on antimicrobial resistance mechanisms and MIC distributions in B. pilosicoli but to some extent the cutoff values proposed for B. hyodysenteriae may be applicable also for monitoring of antimicrobial susceptibility in B. pilosicoli.

Antimicrobial susceptibility of porcine Brachyspira hyodysenteriae and Brachyspira pilosicoli isolated in Sweden between 1990 and 2010

PubMed Central

2012-01-01

Background The anaerobic spirochetes Brachyspira hyodysenteriae and Brachyspira pilosicoli cause diarrheal diseases in pigs. Their fastidious nature has hampered standardization of methods for antimicrobial susceptibility testing. For monitoring of antimicrobial susceptibility wild type cutoff values are needed to define where the wild type distribution of MICs ends and no approved cutoffs are available for Brachyspira spp. In this study antimicrobial susceptibility data for both species (in total 906 isolates) were compiled and analyzed and wild type cut off values for B. hyodysenteriae proposed. Methods The MICs of tiamulin, valnemulin, tylosin, tylvalosin, doxycycline and lincomycin were determined by broth dilution in brain heart infusion broth supplemented with 10% fetal calf serum. Results The compiled MICs from the broth dilution tests of the B. hyodysenteriae type strain, B78T (ATCC® 27164T), showed that the method yields reproducible results. In an international perspective the frequencies of isolates with decreased antimicrobial susceptibility were low among both B. hyodysenteriae and B. pilosicoli. However, in B. pilosicoli a constant level of 10-15% isolates with tiamulin MICs >4 μg/ml was detected between 2002 and 2010 and in B. hyodysenteriae a gradual increase in tiamulin MICs was seen between 1990 and 2003 although this increase has ceased during the last years. The wild type cutoff values proposed for B. hyodysenteriae are: tiamulin >0.25 μg/ml, valnemulin >0.125 μg/ml, tylosin >16 μg/ml, tylvalosin >1 μg/ml, lincomycin >1 μg/ml and doxycycline >0.5 μg/ml. Conclusions The broth dilution method used in this study has over the years generated tightly grouped MIC populations for the field isolates and reproducible results for the control strain B78T and is therefore a suitable antimicrobial susceptibility test method for monitoring of Brachyspira spp. Here we propose wild type cutoff values for six antimicrobial agents for B. hyodysenteriae tested by broth dilution based on MIC distributions and the current knowledge on mechanisms of resistance in this species. There are few studies on antimicrobial resistance mechanisms and MIC distributions in B. pilosicoli but to some extent the cutoff values proposed for B. hyodysenteriae may be applicable also for monitoring of antimicrobial susceptibility in B. pilosicoli. PMID:22998753

Clinical resistance and decreased susceptibility in Streptococcus suis isolates from clinically healthy fattening pigs.

PubMed

Callens, Bénédicte F; Haesebrouck, Freddy; Maes, Dominiek; Butaye, Patrick; Dewulf, Jeroen; Boyen, Filip

2013-04-01

Streptococcus suis (S. suis) has often been reported as an important swine pathogen and is considered as a new emerging zoonotic agent. Consequently, it is important to be informed on its susceptibility to antimicrobial agents. In the current study, the Minimum Inhibitory Concentration (MIC) population distribution of nine antimicrobial agents has been determined for nasal S. suis strains, isolated from healthy pigs at the end of the fattening period from 50 closed or semiclosed pig herds. The aim of the study was to report resistance based on both clinical breakpoints (clinical resistance percentage) and epidemiological cutoff values (non-wild-type percentage). Non-wild-type percentages were high for tetracycline (98%), lincomycin (92%), tilmicosin (72%), erythromycin (70%), tylosin (66%), and low for florfenicol (0%) and enrofloxacin (0.3%). Clinical resistance percentages were high for tetracycline (95%), erythromycin (66%), tylosin (66%), and low for florfenicol (0.3%) and enrofloxacin (0.3%). For tiamulin, for which no clinical breakpoint is available, 57% of the isolates did not belong to the wild-type population. Clinical resistance and non-wild-type percentages differed substantially for penicillin. Only 1% of the tested S. suis strains was considered as clinically resistant, whereas 47% of the strains showed acquired resistance when epidemiological cutoff values were used. In conclusion, MIC values for penicillin are gradually increasing, compared to previous reports, although pigs infected with strains showing higher MICs may still respond to treatment with penicillin. The high rate of acquired resistance against tiamulin has not been reported before. Results from this study clearly demonstrate that the use of different interpretive criteria contributes to the extent of differences in reported antimicrobial resistance results. The early detection of small changes in the MIC population distribution of isolates, while clinical failure may not yet be observed, provides the opportunity to implement appropriate risk management steps.

Drug Development and Conservation of Biodiversity in West and Central Africa

DTIC Science & Technology

2001-05-01

sensitive and -resistant isolates of Trichomonas vaginalis and 18 were tested against the veterinary parasite Tritrichomonas foetus . Of those tested vs...T. vaginalis, three had MIC values of 0.3-0.6 mg/ml and two extracts tested vs. T. foetus had MIC values of 0.3-0.6 mg/ml. These studies are

Relevant role of efflux pumps in high levels of rifaximin resistance in Escherichia coli clinical isolates.

PubMed

Gomes, C; Ruiz, L; Pons, M J; Ochoa, T J; Ruiz, J

2013-09-01

Enteropathogens have shown a high level of resistance against commonly used antibacterial drugs in Peru and it is necessary to explore alternative treatments. The aim of this study was to analyse the in vitro activity of rifaximin against diarrhoeagenic and commensal Escherichia coli in children less than 2 years of age. The minimal inhibitory concentration (MIC) to rifampicin and rifaximin was determined for 210 strains in the presence and absence of phenyl-arginine-β-naphthylamide (PAβN) and the mechanisms of resistance were investigated. The MIC levels ranged between 8 and >256 mg/litre and the predominant mechanism of resistance to rifaximin was the efflux pumps inhibited by PAβN in 95.2% of the isolates. The present MIC values are higher than those observed in other studies. Efflux pumps inhibited by PAβN were the cause of the rifaximin resistance in the majority of cases and suggest the presence of an environmental selective pressure. Consequently, rifaximin should be used with caution in the treatment of diarrhoea in Peru.

Antimicrobial activity of five essential oils from lamiaceae against multidrug-resistant Staphylococcus aureus.

PubMed

Kot, Barbara; Wierzchowska, Kamila; Piechota, Małgorzata; Czerniewicz, Paweł; Chrzanowski, Grzegorz

2018-06-11

Analysis of Lamiaceae essential oils (EOs) by GC-FID-MS revealed the presence as the major constituents of linalool (16.8%), linalyl acetate (15.7%) in Lavandula angustifolia, menthol (29.0%), menthone (22.7%), menthyl acetate (19.2%) in Mentha x piperita, terpinen-4-ol (27.1%), (E)-sabinene hydrate (12.1%), γ-terpinene (10.0%) in Origanum majorana, α-thujone (19.5%), camphor (19.0%), viridiflorol (13.5%) in Salvia officinalis, thymol (61.9%), p-cymene (10.0%), γ-terpinene (10.0%) in Thymus vulgaris. Based on the MIC and MBC values (0.09-0.78 mg/mL) and ratio MBC/MIC showed that EO from T. vulgaris (TO) had the strong inhibitory and bactericidal effect against multidrug-resistant Staphylococcus aureus. The bacterial cells were total killed by TO at 2MIC concentration after 6 h. The higher concentrations of other EOs were needed to achieve bactericidal effects. The strong bactericidal effect of TO against these bacteria indicates the possibility of topical use of TO but it requires research under clinical conditions.

Monitoring of antimicrobial susceptibility of Streptococcus suis in the Netherlands, 2013-2015.

PubMed

van Hout, Jobke; Heuvelink, Annet; Gonggrijp, Maaike

2016-10-15

The objective of the present study was to analyse the in vitro antimicrobial susceptibility of Streptococcus suis isolates from post-mortem samples from pigs in the Netherlands. S. suis isolates originated from diagnostic submissions of pigs sent to the Pathology Department of GD Animal Health, from April 2013 till June 2015. Minimal inhibitory concentrations (MICs) of in total 15 antimicrobials were assessed by broth microdilution following CLSI recommendations. MIC 50 and MIC 90 values were determined and MICs were interpreted as susceptible, intermediate and resistant using CLSI veterinary breakpoints (when available). Emergence of resistance among S. suis (n=1163) derived from clinical submissions of pigs appeared to be limited. Resistance to ampicillin, ceftiofur, clindamycin, enrofloxacin, florfenicol, penicillin, trimethoprim/sulfamethoxazole and tetracycline was 0.3%, 0.5%, 48.1%, 0.6%, 0.1%, 0.5%, 3.0%, and 78.4%, respectively. Cross-resistance between penicillin and ampicillin appeared to be incomplete. MIC values of erythromycin, clindamycin, neomycin, penicillin and tilmicosin for isolates originating from grower/finisher pigs were significantly more often lower than the MIC values of isolates from suckling/weaned piglets. It has to be kept in mind that these results represent only part of the Dutch pig population and it can be discussed whether this is a representative sample. Interpretation of the MIC results of (clinically relevant) antimicrobials tested for treatment of S. suis infection is strongly hampered by the lack of CLSI-defined veterinary clinical breakpoints that are animal species- and body site-specific. Therefore, and to conduct a clinically reliable monitoring of antimicrobial susceptibility of veterinary pathogens, more species- and organ-specific veterinary breakpoints are urgently needed. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of macrophage inhibitory cytokine-1 with nutritional status, body composition and bone mineral density in patients with anorexia nervosa: the influence of partial realimentation.

PubMed

Dostálová, Ivana; Kaválková, Petra; Papežová, Hana; Domluvilová, Daniela; Zikán, Vít; Haluzík, Martin

2010-04-23

Macrophage inhibitory cytokine-1 (MIC-1) is a key inducer of cancer-related anorexia and weight loss. However, its possible role in the etiopathogenesis of nutritional disorders of other etiology such as anorexia nervosa (AN) is currently unknown. We measured fasting serum concentrations of MIC-1 in patients with AN before and after 2-month nutritional treatment and explored its relationship with nutritional status, metabolic and biochemical parameters. Sixteen previously untreated women with AN and twenty-five normal-weight age-matched control women participated in the study. We measured serum concentrations of MIC-1 and leptin by ELISA, free fatty acids by enzymatic colorimetric assay, and biochemical parameters by standard laboratory methods; determined resting energy expenditure by indirect calorimetry; and assessed bone mineral density and body fat content by dual-energy X-ray absorptiometry. ANOVA, unpaired t-test or Mann-Whitney test were used for groups comparison as appropriate. The comparisons of serum MIC-1 levels and other studied parameters in patients with AN before and after partial realimentation were assessed by paired t-test or Wilcoxon Signed Rank Test as appropriate. At baseline, fasting serum MIC-1 concentrations were significantly higher in patients with AN relative to controls. Partial realimentation significantly reduced serum MIC-1 concentrations in patients with AN but it still remained significantly higher compared to control group. In AN group, serum MIC-1 was inversely related to Buzby nutritional risk index, serum insulin-like growth factor-1, serum glucose, serum total protein, serum albumin, and lumbar bone mineral density and it significantly positively correlated with the duration of AN and age. MIC-1 concentrations in AN patients are significantly higher relative to healthy women. Partial realimentation significantly decreased MIC-1 concentration in AN group. Clinical significance of these findings needs to be further clarified.

Evaluation of the in vitro activity of levornidazole, its metabolites and comparators against clinical anaerobic bacteria.

PubMed

Hu, Jiali; Zhang, Jing; Wu, Shi; Zhu, Demei; Huang, Haihui; Chen, Yuancheng; Yang, Yang; Zhang, Yingyuan

2014-12-01

This study evaluated the in vitro anti-anaerobic activity and spectrum of levornidazole, its metabolites and comparators against 375 clinical isolates of anaerobic bacteria, including Gram-negative bacilli (181 strains), Gram-negative cocci (11 strains), Gram-positive bacilli (139 strains) and Gram-positive cocci (44 strains), covering 34 species. Minimum inhibitory concentrations (MICs) of levornidazole, its five metabolites and three comparators against these anaerobic isolates were determined by the agar dilution method. Minimum bactericidal concentrations (MBCs) of levornidazole and metronidazole were measured against 22 strains of Bacteroides fragilis. Levornidazole showed good activity against B. fragilis, other Bacteroides spp., Clostridium difficile, Clostridium perfringens and Peptostreptococcus magnus, evidenced by MIC90 values of 0.5, 1, 0.25, 2 and 1mg/L, respectively. The activity of levornidazole and the comparators was poor for Veillonella spp. Generally, levornidazole displayed activity similar to or slightly higher than that of metronidazole, ornidazole and dextrornidazole against anaerobic Gram-negative bacilli, Gram-positive bacilli and Gram-positive cocci, especially B. fragilis. Favourable anti-anaerobic activity was also seen with levornidazole metabolites M1 and M4 but not M2, M3 or M5. For the 22 clinical B. fragilis strains, MBC50 and MBC90 values of levornidazole were 2mg/L and 4mg/L, respectively. Both MBC50/MIC50 and MBC90/MIC90 ratios of levornidazole were 4, similar to those of metronidazole. Levornidazole is an important anti-anaerobic option in clinical settings in terms of its potent and broad-spectrum in vitro activity, bactericidal property, and the anti-anaerobic activity of its metabolites M1 and M4. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Wild-type MIC distribution and epidemiological cut-off values in clinical Legionella pneumophila serogroup 1 isolates.

PubMed

Bruin, Jacob P; Ijzerman, Ed P F; den Boer, Jeroen W; Mouton, Johan W; Diederen, Bram M W

2012-01-01

The purpose of this study was to establish wild-type (WT) distributions and determine the epidemiological cut-off values (ECOFF) in clinical L. pneumophila serogroup 1 isolates for 10 antimicrobials commonly used for the treatment of Legionella infections using a method feasible in a routine clinical laboratory. MICs of 183 clinical L. pneumophila serogroup 1 isolates, collected as part of an outbreak detection program, were tested using E-test methodology on buffered charcoal yeast extract agar supplemented with α-ketoglutarate (BCYE-α). The MICs were read after 2 days of incubation at 35 °C with increased humidity and without CO(2). ECOFFs were determined according to EUCAST methodology and expressed as WT ≤ X mg/L. All antimicrobials showed a WT distribution, although the width varied from 2 two-fold dilutions to 8 dilutions, depending on antibiotic class. The ECOFFs determined were 1.0 mg/L for ciprofloxacin, 0.50 mg/L for levofloxacin, 1.0 mg/L for moxifloxacin, 1.0 mg/L for erythromycin, 1.0 mg/L for azithromycin, 0.50 mg/L for clarithromycin, 1.0 mg/L for cefotaxime, 0.032 mg/L for rifampicin, 16 mg/L for tigecycline, and 8 mg/L for doxycycline. All isolates were inhibited by low concentrations of the fluoroquinolones and macrolides tested, with somewhat higher MICs for the fluoroquinolones. Rifampicin was found to be the most active against L. pneumophila isolates in vitro. These data can be used as a reference for the detection of resistance in clinical L. pneumophila isolates and as a setting of clinical breakpoints. Copyright © 2012 Elsevier Inc. All rights reserved.

Antibacterial activity of selected Malaysian honey

PubMed Central

2013-01-01

Background Antibacterial activity of honey is mainly dependent on a combination of its peroxide activity and non-peroxide components. This study aims to investigate antibacterial activity of five varieties of Malaysian honey (three monofloral; acacia, gelam and pineapple, and two polyfloral; kelulut and tualang) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Methods Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed for semi-quantitative evaluation. Agar well diffusion assay was used to investigate peroxide and non-peroxide activities of honey. Results The results showed that gelam honey possessed lowest MIC value against S. aureus with 5% (w/v) MIC and MBC of 6.25% (w/v). Highest MIC values were shown by pineapple honey against E. coli and P. aeruginosa as well as acacia honey against E. coli with 25% (w/v) MIC and 50% (w/v) MBC values. Agar inhibition assay showed kelulut honey to possess highest total antibacterial activity against S. aureus with 26.49 equivalent phenol concentrations (EPC) and non-peroxide activity of 25.74 EPC. Lowest antibacterial activity was observed in acacia honey against E. coli with total activity of 7.85 EPC and non-peroxide activity of 7.59 EPC. There were no significant differences (p > 0.05) between the total antibacterial activities and non-peroxide activities of Malaysian honey. The intraspecific correlation between MIC and EPC of E. coli (r = -0.8559) was high while that between MIC and EPC of P. aeruginosa was observed to be moderate (r = -0.6469). S. aureus recorded a smaller correlation towards the opposite direction (r = 0.5045). In contrast, B.cereus showed a very low intraspecific correlation between MIC and EPC (r = -0.1482). Conclusions Malaysian honey, namely gelam, kelulut and tualang, have high antibacterial potency derived from total and non-peroxide activities, which implies that both peroxide and other constituents are mutually important as contributing factors to the antibacterial property of honey. PMID:23758747

Antibacterial activity of selected Malaysian honey.

PubMed

Zainol, Mohd Izwan; Mohd Yusoff, Kamaruddin; Mohd Yusof, Mohd Yasim

2013-06-10

Antibacterial activity of honey is mainly dependent on a combination of its peroxide activity and non-peroxide components. This study aims to investigate antibacterial activity of five varieties of Malaysian honey (three monofloral; acacia, gelam and pineapple, and two polyfloral; kelulut and tualang) against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed for semi-quantitative evaluation. Agar well diffusion assay was used to investigate peroxide and non-peroxide activities of honey. The results showed that gelam honey possessed lowest MIC value against S. aureus with 5% (w/v) MIC and MBC of 6.25% (w/v). Highest MIC values were shown by pineapple honey against E. coli and P. aeruginosa as well as acacia honey against E. coli with 25% (w/v) MIC and 50% (w/v) MBC values. Agar inhibition assay showed kelulut honey to possess highest total antibacterial activity against S. aureus with 26.49 equivalent phenol concentrations (EPC) and non-peroxide activity of 25.74 EPC. Lowest antibacterial activity was observed in acacia honey against E. coli with total activity of 7.85 EPC and non-peroxide activity of 7.59 EPC. There were no significant differences (p > 0.05) between the total antibacterial activities and non-peroxide activities of Malaysian honey. The intraspecific correlation between MIC and EPC of E. coli (r = -0.8559) was high while that between MIC and EPC of P. aeruginosa was observed to be moderate (r = -0.6469). S. aureus recorded a smaller correlation towards the opposite direction (r = 0.5045). In contrast, B.cereus showed a very low intraspecific correlation between MIC and EPC (r = -0.1482). Malaysian honey, namely gelam, kelulut and tualang, have high antibacterial potency derived from total and non-peroxide activities, which implies that both peroxide and other constituents are mutually important as contributing factors to the antibacterial property of honey.

Antistaphylococcal activity of CG400549, a new experimental FabI inhibitor, compared with that of other agents.

PubMed

Bogdanovich, Tatiana; Clark, Catherine; Kosowska-Shick, Klaudia; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C

2007-11-01

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 microg/ml, with MIC(50) and MIC(90) values of 0.25 microg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 microg/ml). The daptomycin MICs were 0.25 to 2.0 microg/ml for methicillin-susceptible and 0.25 to 4.0 microg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested.

Implementing Electric Potential Difference as a New Practical Parameter for Rapid and Specific Measurement of Minimum Inhibitory Concentration of Antibiotics.

PubMed

Mobasheri, Nasrin; Karimi, Mehrdad; Hamedi, Javad

2018-06-05

New methods to determine antimicrobial susceptibility of bacterial pathogens especially the minimum inhibitory concentration (MIC) of antibiotics have great importance in pharmaceutical industry and treatment procedures. In the present study, the MIC of several antibiotics was determined against some pathogenic bacteria using macrodilution test. In order to accelerate and increase the efficiency of culture-based method to determine antimicrobial susceptibility, the possible relationship between the changes in some physico-chemical parameters including conductivity, electrical potential difference (EPD), pH and total number of test strains was investigated during the logarithmic phase of bacterial growth in presence of antibiotics. The correlation between changes in these physico-chemical parameters and growth of bacteria was statistically evaluated using linear and non-linear regression models. Finally, the calculated MIC values in new proposed method were compared with the MIC derived from macrodilution test. The results represent significant association between the changes in EPD and pH values and growth of the tested bacteria during the exponential phase of bacterial growth. It has been assumed that the proliferation of bacteria can cause the significant changes in EPD values. The MIC values in both conventional and new method were consistent to each other. In conclusion, cost and time effective antimicrobial susceptibility test can be developed based on monitoring the changes in EPD values. The new proposed strategy also can be used in high throughput screening of biocompounds for their antimicrobial activity in a relatively shorter time (6-8 h) in comparison with the conventional methods.

The anchor-based minimal important change, based on receiver operating characteristic analysis or predictive modeling, may need to be adjusted for the proportion of improved patients.

PubMed

Terluin, Berend; Eekhout, Iris; Terwee, Caroline B

2017-03-01

Patients have their individual minimal important changes (iMICs) as their personal benchmarks to determine whether a perceived health-related quality of life (HRQOL) change constitutes a (minimally) important change for them. We denote the mean iMIC in a group of patients as the "genuine MIC" (gMIC). The aims of this paper are (1) to examine the relationship between the gMIC and the anchor-based minimal important change (MIC), determined by receiver operating characteristic analysis or by predictive modeling; (2) to examine the impact of the proportion of improved patients on these MICs; and (3) to explore the possibility to adjust the MIC for the influence of the proportion of improved patients. Multiple simulations of patient samples involved in anchor-based MIC studies with different characteristics of HRQOL (change) scores and distributions of iMICs. In addition, a real data set is analyzed for illustration. The receiver operating characteristic-based and predictive modeling MICs equal the gMIC when the proportion of improved patients equals 0.5. The MIC is estimated higher than the gMIC when the proportion improved is greater than 0.5, and the MIC is estimated lower than the gMIC when the proportion improved is less than 0.5. Using an equation including the predictive modeling MIC, the log-odds of improvement, the standard deviation of the HRQOL change score, and the correlation between the HRQOL change score and the anchor results in an adjusted MIC reflecting the gMIC irrespective of the proportion of improved patients. Adjusting the predictive modeling MIC for the proportion of improved patients assures that the adjusted MIC reflects the gMIC. We assumed normal distributions and global perceived change scores that were independent on the follow-up score. Additionally, floor and ceiling effects were not taken into account. Copyright © 2017 Elsevier Inc. All rights reserved.

Failure of Quality Control Measures To Prevent Reporting of False Resistance to Imipenem, Resulting in a Pseudo-Outbreak of Imipenem-Resistant Pseudomonas aeruginosa

PubMed Central

Carmeli, Yehuda; Eichelberger, Karen; Soja, Don; Dakos, Joanna; Venkataraman, Lata; DeGirolami, Paola; Samore, Matthew

1998-01-01

False results showing an outbreak of Pseudomonas aeruginosa with resistance to imipenem were traced to a defective lot of microdilution MIC testing panels. These panels contained two- to threefold lower concentrations of imipenem than expected and resulted in artifactual two- to fourfold increases in MICs of imipenem. The quality-control MIC results for Pseudomonas aeruginosa ATCC 27853 were 4 μg/ml, the highest value within the range recommended by the National Committee for Clinical Laboratory Standards. We recommend that this value be considered out of the quality-control range. PMID:9466787

Silver nanoparticles: Antimicrobial activity, cytotoxicity, and synergism with N-acetyl cysteine.

PubMed

Hamed, Selwan; Emara, Mohamed; Shawky, Riham M; El-Domany, Ramadan A; Youssef, Tareq

2017-08-01

The fast progression of nanotechnology has led to novel therapeutic interventions. Antimicrobial activities of silver nanoparticles (Ag NPs) were tested against standard ATCC strains of Staphylococcus aureus (ATCC 9144), Escherichia coli (O157:H7), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 90028) in addition to 60 clinical isolates collected from cancer patients. Antimicrobial activity was tested by disk diffusion method and MIC values for Ag NPs alone and in combination with N-acetylcysteine (NAC) against tested pathogens were determined by broth microdilution method. Ag NPs showed a robust antimicrobial activity against all tested pathogens and NAC substantially enhanced the antimicrobial activity of Ag NPs against all tested pathogens. Synergism between Ag NPs and NAC has been confirmed by checkerboard assay. The effect of Ag NPs on tested pathogens was further scrutinized by Transmission Electron Microscope (TEM) which showed disruption of cell wall in both bacteria and fungi. Ag NPs abrogated the activity of respiratory chain dehydrogenase of all tested pathogens and released muramic acid content from S. aureus in culture. The cytotoxic effect of Ag NPs alone and in combination with NAC was examined using human HepG2 cells and this revealed no cytotoxicity at MIC values of Ag NPs and interestingly, NAC reduced the cytotoxic effect of Ag NPs at concentrations higher than their MIC values. Taken together, Ag NPs have robust antimicrobial activity and NAC substantially enhances their antimicrobial activities against MDR pathogens which would provide a novel safe, effective, and inexpensive therapeutic approach to control the prevalence of MDR pathogens. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma-based determination of inorganic contaminants in waste of electric and electronic equipment after microwave-induced combustion

NASA Astrophysics Data System (ADS)

Mello, Paola A.; Diehl, Lisarb O.; Oliveira, Jussiane S. S.; Muller, Edson I.; Mesko, Marcia F.; Flores, Erico M. M.

2015-03-01

A systematic study was performed for the determination of inorganic contaminants in polymeric waste from electrical and electronic equipment (EEE) for achieving an efficient digestion to minimize interferences in determination using plasma-based techniques. The determination of As, Br, Cd, Co, Cr, Cu, Ni, Pb, Sb, and Zn by inductively coupled plasma mass spectrometry (ICP-MS) and also by inductively coupled plasma optical emission spectrometry (ICP OES) was carried out after digestion using microwave-induced combustion (MIC). Arsenic and Hg were determined by flow-injection chemical vapor generation inductively coupled plasma mass spectrometry (FI-CVG-ICP-MS). Dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) with ammonia was also used for Cr determination. The suitability of MIC for digestion of sample masses up to 400 mg was demonstrated using microcrystalline cellulose as aid for combustion of polymers from waste of EEEs that usually contain flame retardants that impair the combustion. The composition and concentration of acid solutions (HNO3 or HNO3 plus HCl) were evaluated for metals and metalloids and NH4OH solutions were investigated for Br absorption. Accuracy was evaluated by comparison of results with those obtained using high pressure microwave-assisted wet digestion (HP-MAWD) and also by the analysis of certified reference material (CRM) of polymer (EC680k-low-density polyethylene). Bromine determination was only feasible using digestion by MIC once losses were observed when HP-MAWD was used. Lower limits of detection were obtained for all analytes using MIC (from 0.005 μg g- 1 for Co by ICP-MS up to 3.120 μg g-1 for Sb by ICP OES) in comparison to HP-MAWD due to the higher sample mass that can be digested (400 mg) and the use of diluted absorbing solutions. The combination of HNO3 and HCl for digestion showed to be crucial for quantitative recovery of some elements, as Cr and Sb. In addition, suitable agreement of Cr to CRM value was only obtained by mixing NH4Cl to samples before combustion. No statistical difference (95% confidence level) was observed between the results obtained for As, Cd, Co, Cr, Cu, Hg, Ni, Pb, Sb, and Zn by MIC and HP-MAWD methods. Agreement with certified values was better than 96% using MIC for all inorganic contaminants. Particularly for Br, MIC was the method of choice for digestion due to the possibility of using diluted alkaline solutions for analyte absorption. Based on the obtained results, MIC can be considered as a suitable method for digestion of polymers from waste of EEEs for further plasma based determination of inorganic contaminants.

In Vitro Antibacterial and Antibiofilm Activities of Chlorogenic Acid against Clinical Isolates of Stenotrophomonas maltophilia including the Trimethoprim/Sulfamethoxazole Resistant Strain

PubMed Central

Karunanidhi, Arunkumar; Thomas, Renjan; van Belkum, Alex; Neela, Vasanthakumari

2013-01-01

The in vitro antibacterial and antibiofilm activity of chlorogenic acid against clinical isolates of Stenotrophomonas maltophilia was investigated through disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill and biofilm assays. A total of 9 clinical S. maltophilia isolates including one isolate resistant to trimethoprim/sulfamethoxazole (TMP/SMX) were tested. The inhibition zone sizes for the isolates ranged from 17 to 29 mm, while the MIC and MBC values ranged from 8 to 16 μg mL−1 and 16 to 32 μg mL−1. Chlorogenic acid appeared to be strongly bactericidal at 4x MIC, with a 2-log reduction in viable bacteria at 10 h. In vitro antibiofilm testing showed a 4-fold reduction in biofilm viability at 4x MIC compared to 1x MIC values (0.085 < 0.397 A 490 nm) of chlorogenic acid. The data from this study support the notion that the chlorogenic acid has promising in vitro antibacterial and antibiofilm activities against S. maltophilia. PMID:23509719

Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

PubMed Central

Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

2016-01-01

Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies. PMID:27031728

Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

PubMed

Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

2016-01-01

Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

Effects of various media on the activity of NXL103 (formerly XRP 2868), a new oral streptogramin, against Haemophilus influenzae.

PubMed

Pankuch, Glenn A; Hoellman, Dianne; Bryskier, André; Lowther, John; Appelbaum, Peter C

2006-11-01

The activity of NXL103 against 108 strains of Haemophilus influenzae was tested using Haemophilus test media (HTM) obtained from various sources. With the exception of those obtained with stored HTM, MICs did not differ significantly, with MIC(50) and MIC(90) values of 0.5 and 0.5 to 1 microg/ml, respectively, in each medium.

Habituation of enterotoxigenic Staphylococcus aureus to Origanum vulgare L. essential oil does not induce direct-tolerance and cross-tolerance to salts and organic acids

PubMed Central

Tavares, Adassa Gama; do Monte, Daniel Farias Marinho; Albuquerque, Allan dos Reis; Sampaio, Fábio Correia; Magnani, Marciane; de Siqueira, José Pinto; de Souza, Evandro Leite

2015-01-01

Enterotoxigenic Staphylococcus aureus strains that were isolated from foods were investigated for their ability to develop direct-tolerance and cross-tolerance to sodium chloride (NaCl), potassium chloride (KCl), lactic acid (LA) and acetic acid (AA) after habituation in sublethal amounts (1/2 of the minimum inhibitory concentration - 1/2 MIC and 1/4 of the minimum inhibitory concentration - 1/4 MIC) of Origanum vulgare L. essential oil (OVEO). The habituation of S. aureus to 1/2 MIC and 1/4 MIC of OVEO did not induce direct-tolerance or cross-tolerance in the tested strains, as assessed by modulation of MIC values. Otherwise, exposing the strains to OVEO at sublethal concentrations maintained or increased the sensitivity of the cells to the tested stressing agents because the MIC values of OVEO, NaCl, KCl, LA and AA against the cells that were previously habituated to OVEO remained the same or decreased when compared with non-habituated cells. These data indicate that OVEO does not have an inductive effect on the acquisition of direct-tolerance or cross-tolerance in the tested enterotoxigenic strains of S. aureus to antimicrobial agents that are typically used in food preservation. PMID:26413067

In vitro activity of cefditoren: antimicrobial efficacy against major respiratory pathogens from Asian countries.

PubMed

Lee, Mi Young; Ko, Kwan Soo; Oh, Won Sup; Park, Sulhee; Lee, Ji-Young; Baek, Jin Yang; Suh, Ji-Yoeun; Peck, Kyong Ran; Lee, Nam Yong; Song, Jae-Hoon

2006-07-01

In this study we evaluated the in vitro activities of cefditoren and 14 other comparator agents against 1025 isolates of major respiratory tract pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and Staphylococcus aureus. Bacterial isolates were collected from 11 Asian countries. The majority of S. pneumoniae isolates (98.8%) were susceptible to cefditoren. The MIC(50) and MIC(90) values (minimum inhibitory concentrations for 50% and 90% of the organisms, respectively) of S. pneumoniae were

[A study for testing the antifungal susceptibility of yeast by the Japanese Society for Medical Mycology (JSMM) method. The proposal of the modified JSMM method 2009].

PubMed

Nishiyama, Yayoi; Abe, Michiko; Ikeda, Reiko; Uno, Jun; Oguri, Toyoko; Shibuya, Kazutoshi; Maesaki, Shigefumi; Mohri, Shinobu; Yamada, Tsuyoshi; Ishibashi, Hiroko; Hasumi, Yayoi; Abe, Shigeru

2010-01-01

The Japanese Society for Medical Mycology (JSMM) method used for testing the antifungal susceptibility of yeast, the MIC end point for azole antifungal agents, is currently set at IC(80). It was recently shown, however that there is an inconsistency in the MIC value between the JSMM method and the CLSI M27-A2 (CLSI) method, in which the end- point was to read as IC(50). To resolve this discrepancy and reassess the JSMM method, the MIC for three azoles, fluconazole, itraconazole and voriconazole were compared to 5 strains of each of the following Candida species: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei, for a total of 25 comparisons, using the JSMM method, a modified JSMM method, and the CLSI method. The results showed that when the MIC end- point criterion of the JSMM method was changed from IC(80) to IC(50) (the modified JSMM method) , the MIC value was consistent and compatible with the CLSI method. Finally, it should be emphasized that the JSMM method, using a spectrophotometer for MIC measurement, was superior in both stability and reproducibility, as compared to the CLSI method in which growth was assessed by visual observation.

[In vitro testing of yeast resistance to antimycotic substances].

PubMed

Potel, J; Arndt, K

1982-01-01

Investigations have been carried out in order to clarify the antibiotic susceptibility determination of yeasts. 291 yeast strains of different species were tested for sensitivity to 7 antimycotics: amphotericin B, flucytosin, nystatin, pimaricin, clotrimazol, econazol and miconazol. Additionally to the evaluation of inhibition zone diameters and MIC-values the influence of pH was examined. 1. The dependence of inhibition zone diameters upon pH-values varies due to the antimycotic tested. For standardizing purposes the pH 6.0 is proposed; moreover, further experimental parameters, such as nutrient composition, agar depth, cell density, incubation time and -temperature, have to be normed. 2. The relation between inhibition zone size and logarythmic MIC does not fit a linear regression analysis when all species are considered together. Therefore regression functions have to be calculated selecting the individual species. In case of the antimycotics amphotericin B, nystatin and pimaricin the low scattering of the MIC-values does not allow regression analysis. 3. A quantitative susceptibility determination of yeasts--particularly to the fungistatical substances with systemic applicability, flucytosin and miconazol, -- is advocated by the results of the MIC-tests.

Effective concentration-based serum pharmacodynamics for antifungal azoles in a murine model of disseminated Candida albicans infection.

PubMed

Maki, Katsuyuki; Kaneko, Shuji

2013-12-01

An assessment of the effective in vivo concentrations of antifungal drugs is important in determining their pharmacodynamics, and therefore, their optimal dosage regimen. Here we establish the effective in vivo concentration-based pharmacodynamics of three azole antifungal drugs (fluconazole, itraconazole, and ketoconazole) in a murine model of disseminated Candida albicans infection. A key feature of this study was the use of a measure of mycelial (m) growth rather than of yeast growth, and pooled mouse sera rather than synthetic media as a growth medium, for determining the minimum inhibitory concentrations (MICs) of azoles for C. albicans (denoted serum mMICs). The serum mMIC assay was then used to measure antifungal concentrations and effects as serum antifungal titers in the serum of treated mice. Both serum mMIC and sub-mMIC values reflected the effective in vivo serum concentrations. Supra-mMIC and mMIC effects exhibited equivalent efficacies and were concentration-independent, while the sub-mMIC effect was concentration-dependent. Following administration of the minimum drug dosage that inhibited an increase in mouse kidney fungal burden, the duration periods of these effects were similar for all drugs tested. The average duration of either the mMIC effect including the supra-mMIC effect, the sub-mMIC effect, or the post-antifungal effect (PAFE) were 6.9, 6.5 and 10.6 h, respectively. Our study suggests that the area under the curve for serum drug concentration versus time, between the serum mMIC and the sub-mMIC, and exposure time above the serum sub-mMIC after the mMIC effect, are major pharmacodynamic parameters. These findings have important implications for effective concentration-based pharmacodynamics of fungal infections treated with azoles.

Antistaphylococcal Activity of CG400549, a New Experimental FabI Inhibitor, Compared with That of Other Agents▿

PubMed Central

Bogdanovich, Tatiana; Clark, Catherine; Kosowska-Shick, Klaudia; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C.

2007-01-01

Among 203 strains of Staphylococcus aureus, the MICs of CG400549 were 0.06 to 1.0 μg/ml, with MIC50 and MIC90 values of 0.25 μg/ml each. All strains were susceptible to linezolid and quinupristin-dalfopristin (MICs, 0.25 to 2.0 μg/ml). The daptomycin MICs were 0.25 to 2.0 μg/ml for methicillin-susceptible and 0.25 to 4.0 μg/ml against methicillin-resistant strains (including vancomycin-intermediate strains). Single-passage selection testing showed low resistance frequencies with CG400549, but multistep analysis showed that CG400549 yielded resistant mutants after 14 to 17 days in all strains tested. PMID:17875997

Interferometry as a tool for evaluating effects of antimicrobial doses on Mycobacterium bovis growth.

PubMed

Machado, Rachel R P; Dutra, Rafael C; Raposo, Nádia R B; Lesche, Bernhard; Gomes, Marlei S; Duarte, Rafael S; Soares, Geraldo Luiz G; Kaplan, Maria Auxiliadora C

2015-12-01

Interferometry was used together with the conventional microplate resazurin assay to evaluate the antimycobacterial properties of essential oil (EO) from fruits of Pterodon emarginatus and also of rifampicin against Mycobacterium bovis. The aim of this work is not only to investigate the potential antimycobacterial activity of this EO, but also to test the interferometric method in comparison with the conventional one. The Minimum Inhibitory Concentration (MIC) values of EO (625 μg/mL) and rifampicin (4 ng/mL) were firstly identified with the microplate method. These values were used as parameters in Drug Susceptibility Tests (DST) with interferometry. The interferometry confirmed the MIC value of EO identified with microplate and revealed a bacteriostatic behavior for this concentration. At 2500 μg/mL interferometry revealed bactericidal activity of the EO. Mycobacterial growth was detected with interferometry at 4 ng/mL of rifampicin and even at higher concentrations. One important difference is that the interferometric method preserves the sample, so that after weeks of quantitative observation, the sample can be used to evaluate the bactericidal activity of the tested drug. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis, Antibacterial Evaluation and QSAR of α-Substituted-N4-Acetamides of Ciprofloxacin and Norfloxacin

PubMed Central

Qandil, Amjad M.; Al-Zoubi, Lorca O.; Al-Bakri, Amal G.; Amawi, Haneen A.; Al-Balas, Qosay A.; Alkatheri, Abdulmalik M.; Albekairy, Abdulkareem M.

2014-01-01

Twenty six α-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar = 2-pyrimidyl) and CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4–0.9 μM, against Staphylococcus aureus than CIPRO, while only compound CD-10 exhibited better activity, 0.1 μM, against Bacillus subtilis than CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (α-phenyl, Ar = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (α-phenyl, Ar = 3-chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 μM against this strain. The NOR derivatives showed lower activity than NOR itself against Staphylococcus aureus, although ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 μM. Two NOR derivatives, ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (α-phenyl, Ar = 3-chlorophenyl) and ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 μM against the same strain. QSAR revealed that while polarity is the major contributing factor in the potency against Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against Bacillus subtilis, with a lesser and variable effect for lipophilicity. PMID:27025747

[In vitro susceptibilities of causative organisms isolated from patients with primary respiratory tract infections to BRL 25000 (clavulanic acid/amoxicillin)].

PubMed

Deguchi, K; Fukayama, S; Nishimura, Y; Yokota, N; Tanaka, S; Oda, S; Matsumoto, Y; Ikegami, R; Sato, K; Fukumoto, T

1985-10-01

The in vitro susceptibilities of various causative organisms recently isolated from patients with primary respiratory tract infections to BRL 25000 (a formulation of amoxicillin, 2 parts, and potassium clavulanate, 1 part), amoxicillin (AMPC), cefaclor (CCL), cephalexin (CEX), cefadroxil (CDX) and cefroxadine (CXD) were determined. beta-Lactamase producing strains were detected by nitrocefin chromogenic method and PCG acidometric method. The frequency of isolation of beta-lactamase production in strains of S. aureus, H. influenzae, B. catarrhalis and K. pneumoniae was 92%, 18%, 36% and 98%, respectively. Against S. aureus strains with MIC values to AMPC of less than or equal to 100 micrograms/ml and CEX of less than or equal to 25 micrograms/ml BRL 25000 showed MIC values in the range 0.39-6.25 micrograms/ml with inocula of 10(6) CFU/ml, while BRL 25000 required 12.5-100 micrograms/ml of concentrations for inhibition of the strains with MIC values to AMPC of greater than 100 micrograms/ml and CEX of greater than or equal to 25 micrograms/ml. Against S. pyogenes and S. pneumoniae BRL 25000 showed MIC values in the range less than 0.024-0.10 micrograms/ml with inocula of 10(6) CFU/ml, which is much more active than CCL, CEX, CDX and CXD and slight less active than AMPC. Against H. influenzae and B. catarrhalis BRL 25000 showed MIC values in the range 0.20-6.25 micrograms/ml with inocula of 10(6) CFU/ml, which showed most potent activity among the agents tested. The activity of BRL 25000 against K. pneumoniae was approximately equal to that of CCL and superior to that of AMPC, CEX, CDX and CXD.

Pharmacodynamics of Ceftolozane plus Tazobactam Studied in an In Vitro Pharmacokinetic Model of Infection.

PubMed

MacGowan, Alasdair P; Noel, Alan R; Tomaselli, Sharon G; Nicholls, Donna; Bowker, Karen E

2016-01-01

Ceftolozane plus tazobactam is an antipseudomonal cephalosporin combined with tazobactam, an established beta-lactamase inhibitor, and has in vitro potency against a range of clinically important β-lactamase-producing bacteria, including most extended-spectrum-β-lactamase (ESBL)-positive Enterobacteriaceae. The pharmacodynamics of β-lactam-β-lactamase inhibitor combinations presents a number of theoretical and practical challenges, including modeling different half-lives of the compounds. In this study, we studied the pharmacodynamics of ceftolozane plus tazobactam against Escherichia coli and Pseudomonas aeruginosa using an in vitro pharmacokinetic model of infection. Five strains of E. coli, including three clinical strains plus two CTX-M-15 (one high and one moderate) producers, and five strains of P. aeruginosa, including two with OprD overexpression and AmpC β-lactamases, were employed. Ceftolozane MICs (E. coli, 0.12 to 0.25 mg/liter, and P. aeruginosa, 0.38 to 8 mg/liter) were determined in the presence of 4 mg/liter tazobactam. Dose ranging of ceftolozane (percentage of time in which the free-drug concentration exceeds the MIC [fT>MIC], 0 to 100%) plus tazobactam (human pharmacokinetics) was simulated every 8 hours, with half-lives (t1/2) of 2.5 and 1 h, respectively. Ceftolozane and tazobactam concentrations were confirmed by high-performance liquid chromatography (HPLC). The ceftolozane-plus-tazobactam fT>MIC values at 24 h for a static effect and a 1-log and 2-log drop in initial inoculum for E. coli were 27.8% ± 5.6%, 33.0% ± 5.6%, and 39.6% ± 8.5%, respectively. CTX-M-15 production did not affect the 24-h fT>MIC for E. coli strains. The ceftolozane-plus-tazobactam fT>MIC values for a 24-h static effect and a 1-log and 2-log drop for P. aeruginosa were 24.9% ± 3.0%, 26.6% ± 3.9%, and 31.2% ± 3.6%. Despite a wide range of absolute MICs, the killing remained predictable as long as the MICs were normalized to the corresponding fT>MIC. Emergence of resistance on 4× MIC plates and 8× MIC plates occurred maximally at an fT>MIC of 10 to 30% and increased as time of exposure increased. The fT>MIC for a static effect for ceftolozane plus tazobactam is less than that observed with other cephalosporins against E. coli and P. aeruginosa and is more similar to the fT>MIC reported for carbapenems. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of Various Media on the Activity of NXL103 (Formerly XRP 2868), a New Oral Streptogramin, against Haemophilus influenzae

PubMed Central

Pankuch, Glenn A.; Hoellman, Dianne; Bryskier, André; Lowther, John; Appelbaum, Peter C.

2006-01-01

The activity of NXL103 against 108 strains of Haemophilus influenzae was tested using Haemophilus test media (HTM) obtained from various sources. With the exception of those obtained with stored HTM, MICs did not differ significantly, with MIC50 and MIC90 values of 0.5 and 0.5 to 1 μg/ml, respectively, in each medium. PMID:17065630

Relationship between the clinical efficacy and AUC/MIC of intravenous ciprofloxacin in Japanese patients with intraabdominal infections.

PubMed

Ohki, Emiko; Yamagishi, Yuka; Mikamo, Hiroshige

2013-10-01

The efficacy of fluoroquinolones (FQs) correlates with the pharmacokinetic/pharmacodynamic (PK-PD) parameter, AUC/MIC. To our knowledge, however, no prospective studies have reported the relationship between FQ efficacy and PK-PD parameters in intraabdominal infection; therefore, we prospectively investigated the relationship between the efficacy of intravenous ciprofloxacin (CPFX IV) and PK-PD parameters. The study included 16 patients diagnosed with peritonitis between 2006 and 2008: 14 patients infected with a single organism and 2 patients infected with more than one organism. Each patient was treated with CPFX IV (300 mg twice daily). The response rate was 56% (9 responders and 7 non-responders). Non-responders were infected with Escherichia coli, Pseudomonas aeruginosa, and Bacteroides fragilis (6 patients were infected with a single organism and 1 with more than one organism). Plasma drug concentrations were measured 1 h and 2 or 4 h after administration of CPFX IV. AUC for 24 h (AUC(0-24))/MIC values was calculated. The range of AUC(0-24)/MIC values in responders [95.3-3628.4 (geometric mean, 521.6)] was significantly different from that in non-responders [7.0-45.2 (geometric mean, 16.5)] (p = 0.001). The target AUC/MIC value of CPFX IV would be considered to be 45-95 in patients with peritonitis.

In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex.

PubMed

Lavollay, M; Dubée, V; Heym, B; Herrmann, J-L; Gaillard, J-L; Gutmann, L; Arthur, M; Mainardi, J-L

2014-05-01

The in vitro activity of cefoxitin and imipenem was compared for 43 strains of the Mycobacterium abscessus complex, mostly isolated from cystic fibrosis patients. The MICs of imipenem were lower than those of cefoxitin, although the number of imipenem-resistant strains was higher according to the CLSI breakpoints. Strain comparisons indicated that the MICs of cefoxitin were significantly higher for Mycobacterium bolletii than for M. abscessus. The MICs of both β-lactams were higher for the rough morphotype than for the smooth morphotype. The clinical impact of the in vitro difference between the activity of imipenem and that of cefoxitin remains to be determined. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

[Emerging pathogen: Candida kefyr (Kluvyeromyces marxianus)].

PubMed

Çuhadar, Tuğba; Kalkancı, Ayşe

2017-10-01

In the central microbiology laboratory of Gazi University Hospital Candida kefyr was isolated from different clinical samples as 5.3% in 2016 and in 2017 this rate increased to 9.3% which was nearly two-fold and this has drawn our attention. The aim of this study was to evaluate the special characteristics, antifungal susceptibility and virulence properties of C.keyfr species. Germ tube, corn meal-tween 80 agar morphology and carbohydrate assimilation profiles on ID32C yeast identification system were used for the diagnosis of Candida species. In this study, DNA sequencing was performed using ITS1 and ITS4 primers amplifying fungal gene between 5.8S and 18S regions of rRNA. Antifungal susceptibility was performed using M27A microdilution method recommended by Clinical and Laboratory Standards Institute (CLSI). Minimum inhibitory concentration (MIC) values for amphotericin B, fluconazole, voriconazole and itraconazole were determined. MIC distribution, MIC50 and MIC90 values and geometric mean (GM) were detected. The existence of virulence factors caseinase, secreted aspartyl proteinase, esterase and phospholipase were investigated in vitro. A total of 865 Candida species were isolated from different clinical samples in the central microbiology laboratory of Gazi University Hospital in 2016. Among them, 46 (5.3%) were C.kefyr. In the first four months of 2017, 30 (9.3%) C.kefyr were identified among 320 Candida isolates. Ten isolates which have shown atypical morphology on corn meal agar were selected. Among these 10 isolates, nine of them were identified as C.kefyr by using ID32C system and DNA sequencing method. Amphotericin B MIC value was 2 µg/ml for one isolate, and fluconazole MIC value was 8 µg/ml for another isolate among 46 isolates. Among the 30 isolates of the year 2017, one of them presented MIC value for fluconazole as 8 µg/ml. No marked antifungal resistance was detected in our isolate group. Caseinase was positive in one C.kefyr isolate, and phospholipase were positive in eight of nine isolates. As a result, the reason of increase in the incidence of this Candida species, which does not show significant resistance and presents mostly phospholipase activity as a virulence factor, should be investigated in more detail.

Antifungal Susceptibility Testing of Malassezia spp. with an Optimized Colorimetric Broth Microdilution Method.

PubMed

Leong, Cheryl; Buttafuoco, Antonino; Glatz, Martin; Bosshard, Philipp P

2017-06-01

Malassezia is a genus of lipid-dependent yeasts. It is associated with common skin diseases such as pityriasis versicolor and atopic dermatitis and can cause systemic infections in immunocompromised individuals. Owing to the slow growth and lipid requirements of these fastidious yeasts, convenient and reliable antifungal drug susceptibility testing assays for Malassezia spp. are not widely available. Therefore, we optimized a broth microdilution assay for the testing of Malassezia that is based on the CLSI and EUCAST assays for Candida and other yeasts. The addition of ingredients such as lipids and esculin provided a broth medium formulation that enabled the growth of all Malassezia spp. and could be read, with the colorimetric indicator resazurin, by visual and fluorescence readings. We tested the susceptibility of 52 strains of 13 Malassezia species to 11 commonly used antifungals. MIC values determined by visual readings were in good agreement with MIC values determined by fluorescence readings. The lowest MICs were found for the azoles itraconazole, posaconazole, and voriconazole, with MIC 90 values of 0.03 to 1.0 μg/ml, 0.06 to 0.5 μg/ml, and 0.03 to 2.0 μg/ml, respectively. All Malassezia spp. were resistant to echinocandins and griseofulvin. Some Malassezia spp. also showed high MIC values for ketoconazole, which is the most widely recommended topical antifungal to treat Malassezia skin infections. In summary, our assay enables the fast and reliable susceptibility testing of Malassezia spp. with a large panel of different antifungals. Copyright © 2017 American Society for Microbiology.

Antifungal Susceptibility Testing of Malassezia spp. with an Optimized Colorimetric Broth Microdilution Method

PubMed Central

Leong, Cheryl; Buttafuoco, Antonino

2017-01-01

ABSTRACT Malassezia is a genus of lipid-dependent yeasts. It is associated with common skin diseases such as pityriasis versicolor and atopic dermatitis and can cause systemic infections in immunocompromised individuals. Owing to the slow growth and lipid requirements of these fastidious yeasts, convenient and reliable antifungal drug susceptibility testing assays for Malassezia spp. are not widely available. Therefore, we optimized a broth microdilution assay for the testing of Malassezia that is based on the CLSI and EUCAST assays for Candida and other yeasts. The addition of ingredients such as lipids and esculin provided a broth medium formulation that enabled the growth of all Malassezia spp. and could be read, with the colorimetric indicator resazurin, by visual and fluorescence readings. We tested the susceptibility of 52 strains of 13 Malassezia species to 11 commonly used antifungals. MIC values determined by visual readings were in good agreement with MIC values determined by fluorescence readings. The lowest MICs were found for the azoles itraconazole, posaconazole, and voriconazole, with MIC90 values of 0.03 to 1.0 μg/ml, 0.06 to 0.5 μg/ml, and 0.03 to 2.0 μg/ml, respectively. All Malassezia spp. were resistant to echinocandins and griseofulvin. Some Malassezia spp. also showed high MIC values for ketoconazole, which is the most widely recommended topical antifungal to treat Malassezia skin infections. In summary, our assay enables the fast and reliable susceptibility testing of Malassezia spp. with a large panel of different antifungals. PMID:28381607

Effect of citral and carvacrol on the susceptibility of Listeria monocytogenes and Listeria innocua to antibiotics.

PubMed

Zanini, S F; Silva-Angulo, A B; Rosenthal, A; Rodrigo, D; Martínez, A

2014-05-01

The aim of this study was to evaluate the antibiotic susceptibility of Listeria innocua (L. innocua) and Listeria monocytogenes (L. monocytogenes) cells in the presence of citral and carvacrol at sublethal concentrations in an agar medium. The presence of terpenes in the L. monocytogenes and L. innocua culture medium provided a reduction in the minimal inhibitory concentration (MIC) of all the antibiotics tested. These effects were dependent on the concentration of terpenes present in the culture medium. The combination of citral and carvacrol potentiated antibiotic activity by reducing the MIC values of bacitracin and colistin from 32.0 and 128.0 μg ml⁻¹ to 1.0 and 2.0 μg ml⁻¹, respectively. Thus, both Listeria species became more susceptible to these drugs. In this way, the colistin and bacitracin resistance of L. monocytogenes and L. innocua was reversed in the presence of terpenes. Results obtained in this study show that the phytochemicals citral and carvacrol potentiate antibiotic activity, reducing the MIC values of cultured L. monocytogenes and L. innocua. Phytochemicals citral and carvacrol potentiate antibiotic activity of erythromycin, bacitracin and colistin by reducing the MIC values of cultured Listeria monocytogenes and Listeria innocua. This effect in reducing the MIC values of the antibiotics tested in both micro-organisms was increased when natural antimicrobials were combined. This finding indicated that the combination among terpenes and antibiotic may contribute in reducing the required dosage of antibiotics due to the possible effect of terpenes on permeation barrier of the micro-organism cell membrane. © 2014 The Society for Applied Microbiology.

Resistance to echinocandin-class antifungal drugs

PubMed Central

Perlin, David S.

2009-01-01

Invasive fungal infections cause morbidity and mortality in severely ill patients, and limited drug classes restrict treatment choices. The echinocandins drugs are the first new class of antifungal compounds that target the fungal cell wall by blocking β-1,3-D-glucan synthase. Elevated MIC values with occasional treatment failure have been reported for strains of Candida. Yet, an uncertain correlation exists between clinical failure and elevated MIC values for the echinocandin drugs. Fungi display several adaptive physiological mechanisms that result in elevated MIC values. However, resistance to echinocandin drugs among clinical isolates is associated with amino acid substitutions in two “hot-spot” regions of Fks1, the major subunit of glucan synthase. The mutations, yielding highly elevated MIC values, are genetically dominant and confer cross-resistance to all echinocandin drugs. Prominent Fks1 mutations decrease the sensitivity of glucan synthase for drug by one thousand-fold or more, and strains harboring such mutations may require a concomitant increase in drug to reduce fungal organ burdens in animal infection models. The Fks1-mediated resistance mechanism is conserved in a wide variety of Candida spp. and can account for intrinsic reduced susceptibility of certain species. Fks1 mutations confer resistance in both yeasts and moulds suggesting that this mechanism is pervasive in the fungal kingdom. PMID:17569573

Susceptibility Profile of Staphylococcus epidermidis and Staphylococcus haemolyticus Isolated from Blood Cultures to Vancomycin and Novel Antimicrobial Drugs over a Period of 12 Years.

PubMed

Pinheiro, Luiza; Brito, Carla Ivo; Pereira, Valéria Cataneli; Oliveira, Adilson; Bartolomeu, Ariane Rocha; Camargo, Carlos Henrique; Cunha, Maria Lourdes Ribeiro Souza

2016-06-01

The aim of this study was to evaluate the antimicrobial susceptibility profile of 85 Staphylococcus epidermidis and 84 Staphylococcus haemolyticus strains isolated from blood cultures to oxacillin, vancomycin, tigecycline, linezolid, daptomycin, and quinupristin/dalfopristin over a period of 12 years. S. epidermidis and S. haemolyticus isolated from blood cultures of inpatients, attended at a teaching hospital, were analyzed for the presence of the mecA gene and by SCCmec typing. The minimum inhibitory concentration (MIC) values of tigecycline, linezolid, daptomycin, quinupristin/dalfopristin, and vancomycin were determined. Isolates exhibiting vancomycin MICs of ≥2 μg/ml were typed by pulsed-field gel electrophoresis (PFGE). The rate of mecA positivity was 92.9% and 100% in S. epidermidis and S. haemolyticus, respectively. The most frequent SCCmec types were type III (53.2%) in S. epidermidis and type I (32.1%) in S. haemolyticus. All isolates were susceptible to linezolid and daptomycin, but 7.1% of S. haemolyticus and 2.3% of S. epidermidis isolates were resistant to tigecycline, and 1.2% each of S. haemolyticus and S. epidermidis were resistant and intermediately resistant to quinupristin/dalfopristin, respectively. S. epidermidis exhibited higher vancomycin MICs (40% with MIC of ≥2 μg/ml). Clonal typing of strains with vancomycin MIC of ≥2 μg/ml revealed the presence of different PFGE types of S. epidermidis and S. haemolyticus over a period of up to 4 years (2002-2004, 2005-2008, 2006-2009, 2010-2011). Despite the observation of a high prevalence of mecA, the clinical strains were fully susceptible to vancomycin and to the new drugs linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. The PFGE types with vancomycin MIC of ≥2 μg/ml exhibited a great diversity of SCCmec cassettes, demonstrating that S. epidermidis and S. haemolyticus may easily acquire these resistance-conferring genetic elements.

Fungicidal efficacy of various honeys against fluconazole-resistant Candida species isolated from HIV+ patients with candidiasis.

PubMed

Shokri, H; Sharifzadeh, A

2017-06-01

Honey is well known to possess a broad spectrum of activity against medically important organisms. The purpose of this study was to assess the antifungal activity of different honeys against 40 fluconazole (FLU) resistant Candida species, including Candida albicans (C. albicans), Candida glabrata, Candida krusei and Candida tropicalis. Three honey samples were collected from northern (Mazandaran, A), southern (Hormozgan, B) and central (Lorestan, C) regions of Iran. A microdilution technique based on the CLSI, M27-A2 protocol was employed to compare the susceptibility of honeys "A", "B" and "C" against different pathogenic Candida isolates. The results showed that different Candida isolates were resistant to FLU, ranging from 64μg/mL to 512μg/mL. All of the honeys tested had antifungal activities against FLU-resistant Candida species, ranging from 20% to 56.25% (v/v) and 25% to 56.25% (v/v) for minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs), respectively. Honey "A" (MIC: 31.59%, v/v) showed higher anti-Candida activity than honey "B" (MIC: 35.99%, v/v) and honey "C" (MIC: 39.2%, v/v). No statistically significant differences were observed among the mean MIC values of the honey samples (P>0.05). The order of overall susceptibility of Candida species to honey samples were; C. krusei>C. glabrata>C. tropicalis>C. albicans (P>0.05). In addition, the mean MICs of Candida strains isolated from the nail, vagina and oral cavity were 33.68%, 36.44% and 39.89%, respectively, and were not significantly different (P>0.05). Overall, varying susceptibilities to the anti-Candida properties of different honeys were observed with four FLU-resistant species of Candida. Further research is needed to assess the efficacy of honey as an inhibitor of candidal growth in clinical trials. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome.

PubMed

McNeil, J Chase; Kok, Eric Y; Forbes, Andrea R; Lamberth, Linda; Hulten, Kristina G; Vallejo, Jesus G; Mason, Edward O; Kaplan, Sheldon L

2016-03-01

Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes. Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine. Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 μg/mL. A vancomycin trough >15 μg/mL was, however, an independent risk factor for AKI. Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

[Mutant prevention concentrations of antibacterial agents to ocular pathogenic bacteria].

PubMed

Liang, Qing-Feng; Wang, Zhi-Qun; Li, Ran; Luo, Shi-Yun; Deng, Shi-Jing; Sun, Xu-Guang

2009-01-01

To establish a method to measure mutant prevention concentration (MPC) in vitro, and to measure MPC of antibacterial agents for ocular bacteria caused keratitis. It was an experimental study. Forty strains of ocular bacteria were separated from cornea in Beijing Institute of Ophthalmology, which included 8 strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Pseudomonas aeruginosa and Klebsiella pneumoniae respectively. The minimal inhibitory concentration (MIC) of the levofloxacin (LVF), ofloxacin (OFL), ciprofloxacin (CIP), norfloxacin (NFL), tobramycin (TOB) and chloromycetin (CHL) were determined by agar dilution method from National Committee of Clinical Laboratory Standard (NCCLS). The MPC were measured by accumulate-bacterial methods with bacterial population inoculated more than 1.2 x 10(10) colony forming units per milliliter with Mueller-Hinton broth and tryptic soy agar plate. With the software of SPSS 11.0, the datum such as the range of MIC, MPC, MIC90 and MPC90 were calculated, and the selection index (MPC90/ MI90) and mutant selection window (MSW) were obtained. The MI90 of LVF and TOB (4 mg/L) to Staphylococcus aureus strains were the lowest. CIP showed the lowest MIC90 (0.25 mg/L) to Pseudomonas aeruginosa among six kinds of antibacterial agents. The MIC90 of LVF to Staphylococcus epidermidis (256 mg/L), Streptococcus pneumoniae (1 mg/L) and Klebsiella pneumoniae (0.25 mg/L) were lower than other antibacterial agents. The MPC90, MSW and the MPC90/MIC90 of levofloxacin showed lower values compared with other antibacterial medicines. From all the datum, the MIC90 of CHL was the highest and the activity was the weakest. Although the activity of LVF was higher to every kind of bacteria, CIP had the highest activity antibacterial to Pseudomonas aeruginosa. The capacity of CHL and TOB was weaker than Quinolones for restricting resistant mutants on ocular bacteria. LVF had the strongest capacity for restricting resistant mutants among Quinolones. LVF has better antibacterial effects and stronger capacity for restricting the selection of resistant mutants on ocular bacteria than other antibacterial agents.

Chemical composition and in vitro evaluation of antioxidant, antimicrobial, cytotoxicity and anti-acetylcholinesterase properties of Tunisian Origanum majorana L. essential oil.

PubMed

Hajlaoui, Hafedh; Mighri, Hedi; Aouni, Mahjoub; Gharsallah, Néji; Kadri, Adel

2016-06-01

This study investigated the chemical composition and evaluated the antioxidant, antimicrobial, cytotoxic and anti-acetylcholinesterase properties of Tunisian Origanum majorana essential oil. The findings showed that the oil exhibited high activity, particularly in terms of reducing power and β-Carotene bleaching, inducing higher IC50 values than BHT. The oil showed an important antimicrobial activity against 25 bacterial and fungal strains. In fact, the IZ, MIC and MBC values recorded for the bacterial strains were in the range of 8 ± 0-18.33 ± 0.57 mm, 0.097-3.125 and 0.39-6.25 mg/mL, respectively. The IZ, MIC and MFC values of the fungal strains varied between 11±0-28 ± 0 mm, 0.058-0.468 mg/mL and 0.234-1.875 mg/mL, respectively. A low cytotoxic effect was observed against cancer (Hep-2 and HT29) and continuous cell lineage (Vero), with CC50 values ranging from 13.73 to 85.63 mg/mL. The oil was also evaluated for anti-acetylcholinesterase effects, which showed that it exhibited significant activity with IC50 values reaching 150.33 ± 2.02 μg/mL. Copyright © 2016 Elsevier Ltd. All rights reserved.

In Vitro Activity of DC-159a, a New Broad-Spectrum Fluoroquinolone, Compared with That of Other Agents against Drug-Susceptible and -Resistant Pneumococci▿

PubMed Central

Clark, Catherine; Smith, Kathy; Ednie, Lois; Bogdanovich, Tatiana; Dewasse, Bonifacio; McGhee, Pamela; Appelbaum, Peter C.

2008-01-01

DC-159a yielded MICs of ≤1 μg/ml against 316 strains of both quinolone-susceptible and -resistant pneumococci (resistance was defined as a levofloxacin MIC ≥4 μg/ml). Although the MICs for DC-159a against quinolone-susceptible pneumococci were a few dilutions higher than those of gemifloxacin, the MICs of these two compounds against 28 quinolone-resistant pneumococci were identical. The DC-159a MICs against quinolone-resistant strains did not appear to depend on the number or the type of mutations in the quinolone resistance-determining region. DC-159a, as well as the other quinolones tested, was bactericidal after 24 h at 2× MIC against 11 of 12 strains tested. Two of the strains were additionally tested at 1 and 2 h, and DC-159a at 4× MIC showed significant killing as early as 2 h. Multistep resistance selection studies showed that even after 50 consecutive subcultures of 10 strains in the presence of sub-MICs, DC-159a produced only two mutants with maximum MICs of 1 μg/ml. PMID:17938189

Antipneumococcal activity of ceftobiprole, a novel broad-spectrum cephalosporin.

PubMed

Kosowska, Klaudia; Hoellman, Dianne B; Lin, Gengrong; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bozdogan, Bülent; Shapiro, Stuart; Appelbaum, Peter C

2005-05-01

Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC(50) and MIC(90) values (microg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1x and 2x the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2x the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2x the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole.

Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin

PubMed Central

Kosowska, Klaudia; Hoellman, Dianne B.; Lin, Gengrong; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bozdogan, Bülent; Shapiro, Stuart; Appelbaum, Peter C.

2005-01-01

Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant Staphylococcus aureus cephalosporin, was very highly active against a panel of 299 drug-susceptible and -resistant pneumococci, with MIC50 and MIC90 values (μg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem, and ertapenem had lower MICs against all pneumococcal strains than amoxicillin, cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did not correlate with penicillin or macrolide susceptibility or resistance. All strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin, vancomycin, and teicoplanin. Time-kill analyses showed that at 1× and 2× the MIC, ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively. Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal against 10 to 12 strains at 2× the MIC. Azithromycin and clarithromycin were slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains at 2× the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin-dalfopristin and daptomycin showed marked killing at early time periods. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to yield mutants with high MICs towards this cephalosporin, and single-passage selection showed very low frequencies of spontaneous mutants with breakthrough MICs towards ceftobiprole. PMID:15855516

In vitro activity of ceftazidime/avibactam against Gram-negative pathogens isolated from pneumonia in hospitalised patients, including ventilated patients.

PubMed

Flamm, Robert K; Nichols, Wright W; Sader, Helio S; Farrell, David J; Jones, Ronald N

2016-03-01

The activities of the novel β-lactam/non-β-lactam β-lactamase inhibitor combination ceftazidime/avibactam and comparators were evaluated against isolates from pneumonia in hospitalised patients including ventilated patients (PHP, pneumonia not designated as VABP; VABP, pneumonia in ventilated patients). Isolates were from the European-Mediterranean region (EuM), China and the USA collected in the SENTRY Antimicrobial Surveillance Program between 2009 and 2011 inclusive. A total of 2393 organisms from PHP were from the EuM, 888 from China and 3213 from the USA; from VABP patients there were 918, 97 and 692 organisms collected, respectively. Among Enterobacteriaceae from PHP, ceftazidime/avibactam MIC90 values against Escherichia coli ranged from 0.25-0.5mg/L and Klebsiella spp. MIC90 values were 0.5mg/L in each region. Among VABP isolates, MIC90 values for ceftazidime/avibactam against E. coli were 0.25mg/L; for Klebsiella spp. from VABP patients, MIC90 values were similar to those obtained against PHP isolates. The MIC of ceftazidime/avibactam was ≤8mg/L against 92-96% of Pseudomonas aeruginosa isolated from PHP patients. Isolates of P. aeruginosa from VABP patients were of lower susceptibility to all antibacterial agents (e.g. depending on region, meropenem susceptibilities were 51.2-69.4% in contrast to 68.3-76.7% among PHP patients). However, ceftazidime/avibactam inhibited 79.2-95.4% of VABP isolates at an MIC of ≤8mg/L. Acinetobacter spp. were resistant to many agents and only rates of susceptibility to colistin were >90% across all regions both for PHP and VABP isolates. Ceftazidime/avibactam was generally active against a high proportion of isolates resistant to ceftazidime from PHP and VAPB patients. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Surface activation of graphene oxide nanosheets by ultraviolet irradiation for highly efficient anti-bacterials

NASA Astrophysics Data System (ADS)

Veerapandian, Murugan; Zhang, Linghe; Krishnamoorthy, Karthikeyan; Yun, Kyusik

2013-10-01

A comprehensive investigation of anti-bacterial properties of graphene oxide (GO) and ultraviolet (UV) irradiated GO nanosheets was carried out. Microscopic characterization revealed that the GO nanosheet-like structures had wavy features and wrinkles or thin grooves. Fundamental surface chemical states of GO nanosheets (before and after UV irradiation) were investigated using x-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy. Minimum inhibitory concentration (MIC) results revealed that UV irradiated GO nanosheets have more pronounced anti-bacterial behavior than GO nanosheets and standard antibiotic, kanamycin. The MIC of UV irradiated GO nanosheets was 0.125 μg ml-1 for Escherichia coli and Salmonella typhimurium, 0.25 μg ml-1 for Bacillus subtilis and 0.5 μg ml-1 for Enterococcus faecalis, ensuring its potential as an anti-infective agent for controlling the growth of pathogenic bacteria. The minimum bactericidal concentration of normal GO nanosheets was determined to be two-fold higher than its corresponding MIC value, indicating promising bactericidal activity. The mechanism of anti-bacterial action was evaluated by measuring the enzymatic activity of β-d-galactosidase for the hydrolysis of o-nitrophenol-β-d-galactopyranoside.

Anti-Candida activity of geraniol involves disruption of cell membrane integrity and function.

PubMed

Sharma, Y; Khan, L A; Manzoor, N

2016-09-01

Candidiasis is a major problem in immunocompromised patients. Candida, an opportunistic fungal pathogen, is a major health concern today as conventional drugs are highly toxic with undesirable side effects. Their fungistatic nature is responsible for drug resistance in continuously evolving strains. Geraniol, an acyclic monoterpene alcohol, is a component of several plant essential oils. In the present study, an attempt has been made to understand the antifungal activity of geraniol at the cell membrane level in three Candida species. With an MIC of 30-130μg/mL, this natural compound was fungicidal at concentrations 2×MIC. There was complete suppression of fungal growth at MIC values (growth curves) and encouragingly geraniol is non-toxic even at the concentrations approaching 5×MIC (hemolysis assay). Exposed cells showed altered morphology, wherein the cells appeared either broken or shrivelled up (SEM studies). Significant reduction was seen in ergosterol levels at sub-MIC and glucose-induced H(+) efflux at concentrations>MIC values. Our results suggest that geraniol disrupts cell membrane integrity by interfering with ergosterol biosynthesis and inhibiting the very crucial PM-ATPase. It may hence be used in the management and treatment of both superficial and invasive candidiasis but further studies are required to elaborate its mode of action. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluation of graphical and statistical representation of analytical signals of spectrophotometric methods

NASA Astrophysics Data System (ADS)

Lotfy, Hayam Mahmoud; Fayez, Yasmin Mohammed; Tawakkol, Shereen Mostafa; Fahmy, Nesma Mahmoud; Shehata, Mostafa Abd El-Atty

2017-09-01

Simultaneous determination of miconazole (MIC), mometasone furaoate (MF), and gentamicin (GEN) in their pharmaceutical combination. Gentamicin determination is based on derivatization with of o-phthalaldehyde reagent (OPA) without any interference of other cited drugs, while the spectra of MIC and MF are resolved using both successive and progressive resolution techniques. The first derivative spectrum of MF is measured using constant multiplication or spectrum subtraction, while its recovered zero order spectrum is obtained using derivative transformation. Beside the application of constant value method. Zero order spectrum of MIC is obtained by derivative transformation after getting its first derivative spectrum by derivative subtraction method. The novel method namely, differential amplitude modulation is used to get the concentration of MF and MIC, while the novel graphical method namely, concentration value is used to get the concentration of MIC, MF, and GEN. Accuracy and precision testing of the developed methods show good results. Specificity of the methods is ensured and is successfully applied for the analysis of pharmaceutical formulation of the three drugs in combination. ICH guidelines are used for validation of the proposed methods. Statistical data are calculated, and the results are satisfactory revealing no significant difference regarding accuracy and precision.

Interpretive criteria of antimicrobial disk susceptibility tests with flomoxef.

PubMed

Grimm, H

1991-01-01

320 recently isolated pathogens, 20 strains from each of 16 species, were investigated using Mueller-Hinton agar and DIN as well as NCCLS standards. The geometric mean of the agar dilution MICs of flomoxef were 0.44 mg/l for Staphylococcus aureus, 0.05 mg/l (Klebsiella oxytoca) to 12.6 mg/l (Enterobacter spp.) for enterobacteriaceae, 33.1 mg/l for Acinetobacter anitratus, 64 mg/l for Enterococcus faecalis, and more than 256 mg/l for Pseudomonas aeruginosa. For disk susceptibility testing of flomoxef a 30 micrograms disk loading and the following interpretation of inhibition zones using the DIN method were recommended: resistant-up to 22 mm (corresponding to MICs of 8 mg/l or more), moderately susceptible-23 to 29 mm (corresponding to MICs from 1 to 4 mg/l), and susceptible-30 mm or more (corresponding to MICs of 0.5 mg/l or less). The respective values for the NCCLS method using the American high MIC breakpoints are: resistant--up to 14 mm (corresponding to MICs of 32 mg/l or more), moderately susceptible--15 to 17 mm (corresponding to MICs of 16 mg/l), and susceptible--18 mm or more (corresponding to MICs of 8 mg/l or less).

Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis.

PubMed

Pereira, Fillipe de Oliveira; Mendes, Juliana Moura; Lima, Igara Oliveira; Mota, Kelly Samara de Lira; Oliveira, Wylly Araújo de; Lima, Edeltrudes de Oliveira

2015-02-01

Trichophyton rubrum is the most common fungus causing chronic dermatophytosis in humans. Antifungal activity of promising agents is of great interest. Geraniol and citronellol are monoterpenes with antimicrobial properties. This study aimed to investigate the inhibitory effects and possible mechanism of antifungal activity of geraniol and citronellol against strains of T. rubrum. The minimum inhibitory concentration (MIC) of each drug against 14 strains was determined by broth microdilution. The effects of the drugs on dry mycelial weight, conidial germination, infectivity on human nail fragments, and morphogenesis of T. rubrum were analyzed. The effects on the cell wall (test with sorbitol) and cell membrane (release of intracellular material and ergosterol biosynthesis) were investigated. MIC values of geraniol ranged between 16 and 256 µg/mL while citronellol showed MIC values from 8 to 1024 µg/mL. The drugs (MIC and 2 × MIC) inhibited the mycelial growth, conidia germination, and fungal growth on nail fragments. The drugs (half of MIC) induced the formation of wide, short, and crooked hyphae in T. rubrum morphology. With sorbitol, geraniol MIC was increased by 64-fold and citronellol by 32-fold. The drugs caused leakage of intracellular material and inhibited ergosterol biosynthesis. The results suggest that the drugs damage cell wall and cell membrane of T. rubrum through a mechanism that seems to involve the inhibition of the ergosterol biosynthesis. This study confirms that geraniol and citronellol can be regarded as potential drugs for controlling T. rubrum growth, with great potential against agents of dermatophytosis.

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.

PubMed

Curis, Emmanuel; Pestre, Vincent; Jullien, Vincent; Eyrolle, Luc; Archambeau, Denis; Morand, Philippe; Gatin, Laure; Karoubi, Matthieu; Pinar, Nicolas; Dumaine, Valérie; Nguyen Van, Jean-Claude; Babinet, Antoine; Anract, Philippe; Salmon, Dominique

2015-08-01

Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome. An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L. Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin. This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

Human Target Attainment Probabilities for Delafloxacin against Escherichia coli and Pseudomonas aeruginosa

PubMed Central

Hoover, Randall; Marra, Andrea; Duffy, Erin; Cammarata, Sue K

2017-01-01

Abstract Background Delafloxacin (DLX) is a broad-spectrum fluoroquinolone antibiotic under FDA review for the treatment of ABSSSI. Previous studies determined DLX bacterial stasis and 1-log10 bacterial reduction free AUC0-24 / MIC (fAUC0-24/MIC) targets for Escherichia coli (EC) and Pseudomonas aeruginosa (PA) in a mouse thigh infection model. The resulting PK/PD targets were used to predict DLX target attainment probabilities (TAP) in humans. Methods Monte Carlo simulations were used to estimate TAP with DLX 300 mg IV, q12hr. Human DLX plasma pharmacokinetics were determined in patients with ABSSSI in a Phase 3 clinical trial. Individual AUC values were analyzed and determined to be log-normally distributed. The parameters of the AUC distribution were used to simulate random values for fAUC24, which then were combined with random MIC values based on 2014–2015 US distributions of skin and soft tissue isolates of EC (n = 108) and PA (n = 40), to calculate PK/PD TAPs. Results DLX fAUC0-24/MIC targets for bacterial stasis and 1-log10 bacterial reduction for EC were 14.5 and 26.2, and for PA were 3.81 and 5.02, respectively. The Monte Carlo simulations for EC predicted TAPs of 98.7% for stasis at an MIC of 0.25 μg/mL, and 99.3% for 1-log10 bacterial reduction at an MIC of 0.12 μg/mL. The simulations for PA predicted TAPs of 97.3% for stasis and 86.5% for 1-log10 bacterial reduction at an MIC of 1 μg/mL. E. coli MIC (ug/mL) Target 0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 Stasis 100 100 100 100 100 97.8 50.4 2.0 1-Log Kill 100 100 100 100 99.3 60.4 5.8 0.0 P. aeruginosa MIC (ug/mL) Target 0.03 0.06 0.12 0.25 0.5 1 2 4 5 Stasis 100 100 100 100 100 97.3 45.9 1.7 0.5 1-Log Kill 100 100 100 100 100 86.5 17.8 0.3 0.1 Conclusion DLX 300 mg IV, q12hr, should achieve fAUC24/MIC ratios that are adequate to treat ABSSSI caused by most contemporary isolates of EC and PA. For EC, isolates with DLX MICs ≤0.25 μg/mL comprised 73% of all isolates. For PA, isolates with DLX MICs ≤1 μg/mL comprised 88% of all isolates. Similar results would be expected for TAP with oral DLX 450 mg, q12hr. Disclosures R. Hoover, Melinta Therapeutics: Consultant, Consulting fee; A. Marra, Melinta Therapeutics: Employee, Salary; E. Duffy, Melinta Therapeutics: Employee, Salary; S. K. Cammarata, Melinta Therapeutics: Employee, Salary

Slime production and proteinase activity of Candida species isolated from blood samples and the comparison of these activities with minimum inhibitory concentration values of antifungal agents.

PubMed

Ozkan, Semiha; Kaynak, Fatma; Kalkanci, Ayse; Abbasoglu, Ufuk; Kustimur, Semra

2005-05-01

Slime and proteinase activity of 54 strains consisting of 19 Candida parapsilosis and 35 C. albicans strains isolated from blood samples were investigated in this study. Ketoconazole, amphothericin B, and fluconazole susceptibility of Candida species were compared with slime production and proteinase activity of these species. For both Candida species, no correlation was detected between the slime activity and minimum inhibitory concentration (MIC) values of the three antifungal agents. For both Candida species no correlation was detected between the proteinase activity and the MIC values of amphothericin B, and fluconazole however, statistically significant difference, was determined between the proteinase activity and MIC values of ketoconazole (p = 0.007). Slime production was determined by using modified Christensen macrotube method and proteinase activity was measured by the method of Staib. Antifungal susceptibility was determined through the guidelines of National Committee for Laboratory Standards (NCCLS M27-A).

Synthesis and Bioactivity Evaluation of N-Arylsulfonylindole Analogs Bearing a Rhodanine Moiety as Antibacterial Agents.

PubMed

Song, Ming-Xia; Li, Song-Hui; Peng, Jiao-Yang; Guo, Ting-Ting; Xu, Wen-Hui; Xiong, Shao-Feng; Deng, Xian-Qing

2017-06-14

Due to the rapidly growing bacterial resistance to antibiotics and the scarcity of novel agents under development, bacterial infections are still a pressing global problem, making new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, urgently needed. In this paper, seven series of N -arylsulfonylindole analogs 5 - 11 bearing rhodanine moieties were synthesized, characterized, and evaluated for antibacterial activity. According to the in vitro antimicrobial results, half of the synthesized compounds showed potent inhibition against four Gram-positive bacteria, with MIC values in the range of 0.5-8 µg/mL. For multidrug-resistant strains, compounds 6a and 6c were the most potent, with MIC values of 0.5 µg/mL, having comparable activity to gatifloxacin, moxiflocaxin and norfloxacin and being 128-fold more potent than oxacillin (MIC = 64 µg/mL) and 64-fold more active than penicillin (MIC = 32 µg/mL) against Staphylococcus aureus ATCC 43300 .

The activity of silver nanoparticles against microalgae of the Prototheca genus.

PubMed

Jagielski, Tomasz; Bakuła, Zofia; Pleń, Małgorzata; Kamiński, Michał; Nowakowska, Julita; Bielecki, Jacek; Wolska, Krystyna I; Grudniak, Anna M

2018-05-01

To investigate the in vitro activity of silver NPs (AgNPs) against pathogenic microalgae of the Prototheca genus. The antialgal potential of AgNPs against Prototheca species of both clinical and environmental origin was assessed from minimum inhibitory (algistatic) and algicidal concentrations. The in vitro cytotoxicity of AgNPs against bovine mammary epithelial cell line was evaluated by means of the standard MTT assay. AgNPs showed a strong killing activity toward Prototheca algae, as the minimal algicidal concentration (MAC) values matched perfectly the corresponding minimum inhibitory concentration (MIC) values for all species (MAC = MIC, 1-4 mg/l), except P. stagnora (MIC > 8 mg/l). The concentrations inhibitory to pathogenic Prototheca spp. (MIC, 1-4 mg/l) were below the concentrations at which any toxicity in epithelial cells could be observed (CC 20 > 6 mg/l). The study emphasizes the potential of AgNPs as a new therapeutic tool for the management of Prototheca infections.

Determination of antibacterial activity of green coffee bean extract on periodontogenic bacteria like Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans: An in vitro study.

PubMed

Bharath, Nagaraj; Sowmya, Nagur Karibasappa; Mehta, Dhoom Singh

2015-01-01

The aim of this study was to evaluate the antibacterial activity of pure green coffee bean extract on periodonto pathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were used to assess the antibacterial effect of pure green coffee bean extract against periodonto pathogenic bacteria by micro dilution method and culture method, respectively. MIC values of Pg, Pi and Aa were 0.2 μg/ml whereas Fn showed sensitive at concentration of 3.125 μg/ml. MBC values mirrors the values same as that of MIC. Antimicrobial activity of pure green coffee bean extract against Pg, Pi, Fn and Aa suggests that it could be recommended as an adjunct to mechanical therapy in the management of periodontal disease.

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.

PubMed

Holmes, Natasha E; Turnidge, John D; Munckhof, Wendy J; Robinson, J Owen; Korman, Tony M; O'Sullivan, Matthew V N; Anderson, Tara L; Roberts, Sally A; Warren, Sanchia J C; Gao, Wei; Howden, Benjamin P; Johnson, Paul D R

2013-04-01

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥ 400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥ 400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

Vancomycin AUC/MIC Ratio and 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia

PubMed Central

Turnidge, John D.; Munckhof, Wendy J.; Robinson, J. Owen; Korman, Tony M.; O'Sullivan, Matthew V. N.; Anderson, Tara L.; Roberts, Sally A.; Warren, Sanchia J. C.; Gao, Wei; Howden, Benjamin P.; Johnson, Paul D. R.

2013-01-01

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a “real-world” context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods. PMID:23335735

NGAL, MIC-1 and CA19-9 in Pancreatic Juice: Pathobiological Implications in Diagnosing Benign and Malignant Disease of the Pancreas

PubMed Central

KAUR, SUKHWINDER; BAINE, MICHAEL J.; GUHA, SUSHOVAN; OCHI, NOBUO; CHAKRABORTY, SUBHANKAR; MALLYA, KAVITA; THOMAS, COLLEEN; CROOK, JULIA; WALLACE, MICHAEL B.; WOODWARD, TIMOTHY A.; JAIN, MANEESH; SINGH, SHAILENDER; SASSON, AARON R.; SKINNER, VERNA; RAIMONDO, MASSIMO; BATRA, SURINDER K.

2012-01-01

Objective Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase–associated lipocalin (NGAL), macrophage inhibitory cytokine-1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases. Methods 105 chronic pancreatitis (CP), pancreatic cancer (PC), and non-pancreatic non-healthy (NPNH, patients with symptoms mimicking pancreatic disease but found to be free of pancreatic pathology) patients underwent endoscopic pancreatic juice collection following secretin-stimulation. NGAL and MIC-1 levels were measured by enzyme-linked immunosorbent assay while CA19-9 was measured by radioimmunoassay. Results NGAL, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of CP and PC patients as compared to NPNH controls (p<0.034). NGAL appeared most promising in differentiating diseased versus non-diseased pancreata (AUCs=0.88–0.91) while MIC-1 was found to be higher in PC than CP patients (p=0.043). Interestingly, MIC-1 levels in diabetic PC patients were higher than in non-diabetic PC (p=0.030) and diabetic CP patients (p=0.087). CA19-9 showed the least ability to distinguish patient groups (AUCs=0.61–0.76). Conclusions Pancreatic juice NGAL shows potential utility in establishing pancreatic etiology in the context of non-specific symptoms while MIC-1 may aid in differentiating PC from CP. PMID:23146921

Myocardial protection during minimally invasive cardiac surgery through right mini-thoracotomy.

PubMed

De Palo, Micaela; Guida, Pietro; Mastro, Florinda; Nanna, Daniela; Quagliara, Teresa A P; Rociola, Ruggiero; Lionetti, Giosuè; Paparella, Domenico

2017-04-01

Myocardial damage is an independent predictor of adverse outcome following cardiac surgery and myocardial protection is one of the key factors to achieve successful outcomes. Cardioplegia with Custodiol is currently the most used cardioplegia during minimally invasive cardiac surgery (MICS). Different randomized controlled trials compared blood and Custodiol cardioplegia in the context of traditional cardiac surgery. No data are available for MICS. The aim of this study was to compare the efficacy of cold blood versus Custodiol cardioplegia during MICS. We retrospectively evaluated 90 patients undergoing MICS through a right mini-thoracotomy in a three-year period. Myocardial protection was performed using cold blood (44 patients, CBC group) or Custodiol (46 patients, Custodiol group) cardioplegia, based on surgeon preference and complexity of surgery. The primary outcomes were post-operative cardiac troponin I (cTnI) and creatine kinase MB (CKMB) serum release and the incidence of Low Cardiac Output Syndrome (LCOS). Aortic cross-clamp and cardiopulmonary bypass times were higher in the Custodiol group. No difference was observed in myocardial injury enzyme release (peak cTnI value was 18±46 ng/ml in CBC and 21±37 ng/ml in Custodiol; p=0.245). No differences were observed for mortality, LCOS, atrial or ventricular arrhythmias onset, transfusions, mechanical ventilation time duration, intensive care unit and total hospital stay. Custodiol and cold blood cardioplegic solutions seem to assure similar myocardial protection in patients undergoing cardiac surgery through a right mini-thoracotomy approach.

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--I. Gram-positive bacteria].

PubMed

Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

2003-10-01

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial susceptibility for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (2,363 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), methicillin-resistant Staphylococcus epidermidis (MRSE), Staphylococcus haemolyticus, Staphylococcus saprophyticus, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, Streptococcus pyogenes, Streptococcus agalactiae, penicillin-susceptible Streptococcus pneumoniae (PSSP), penicillin-intermediate resistant S. pneumoniae (PISP), penicillin-resistant S. pneumoniae (PRSP), Streptococcus milleri group and Peptostreptococcus spp. The antibacterial activity of CZOP either against MSSA or MSSE was preferable (MIC90: 2 or 0.5 micrograms/mL) and comparable to those of other cephems. CZOP was also effective on MRSE (MIC90: 16 micrograms/mL) but not on MRSA. CZOP and other cephems had low antibacterial activity against S. haemolyticus (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than those of other cephems, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (32 vs 1-2 micrograms/mL). The antibacterial activity of CZOP against E. faecalis was comparable to that of cefpirome (CPR; MIC90: 16 micrograms/mL) and higher than those of other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, like other drugs. The antibacterial activity of CZOP against S. pyogenes was as potent as those of cefotiam and CPR (MIC90: < or = 0.063 microgram/mL), and, against S. agalactiae, was also preferable (MIC90: 0.125 microgram/mL). CZOP indicated preferable antibacterial activity either against PSSP, PISP, or PRSP (MIC90: 0.25, 1, or 2 micrograms/mL). The antibacterial activity of CZOP against S. milleri group was also preferable, but the MIC90 of CZOP in 2001 was higher than those in 1996-2000 (4 vs 0.5 micrograms/mL). The antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than those of cefazolin and cefmetazole. The resistance ratio estimated from breakpoint MIC of CZOP was 95.9% in MRSA, 93.5% in PRSP, 63.3% in PISP, 35.8% in S. haemolyticus, 27.9% in E. faecalis, and 13.3% MRSE. Those resistance ratios were comparable to those for cefepime (CFPM), but E. faecalis showed 91.2% for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against these species. In correlation of drug susceptibility, 40.3% of PRSP was not inhibited at breakpoint MIC either CZOP or CFPM while 69.2% at breakpoint MIC either CZOP or ceftazidime. In conclusion, the antibacterial activities of CZOP against the Gram-positive bacteria obtained from the 6-year duration study were consistent with the results from the studies performed until the new drug application approval. A decline in the sensitivities of S. saprophyticus, S. milleri group, PISP, and PRSP to CZOP, however, was suggested.

Antifungal metabolites from Schinopsis balansae Engl (Anacardiaceae): isolation, identification and evidences of their mode of action on Fusarium graminearum Schwabe.

PubMed

Aristimuño Ficoseco, María Eugenia; Sequin, Christian Javier; Aceñolaza, Pablo Gilberto; Vattuone, Marta Amelia; Catalán, Cesar Atilio N; Sampietro, Diego Alejandro

2017-06-01

An antifungal activity-directed fractionation of leaf constituents from Schinopsis balansae on Fusarium graminearum yielded a fraction mainly made of a mixture of four 3-n-heptadec(en)ylcatechols (PALK). The PALK fraction showed on macroconidia germination a MIC 100 value of 500 μg/mL which was twofold higher than that required for prothioconazole (MIC 100  = 250 μg/mL). Sublethal concentrations of PALK modify the morphogenesis in germinating macroconidia, and decreased fungal production of H 2 O 2 and deoxynivalenol biosynthesis at early fungal growth. Mixes of PALK and prothioconazole showed a synergic interaction. Our findings suggest that PALK constituents might restrict the adherence of F. graminearum to the surface of its hosts and its virulence on susceptible cereals. They deserve further research as additives of azole fungicides against F. graminearum.

Relationship of In Vitro Susceptibility to Moxifloxacin and In Vivo Clinical Outcome in Bacterial Keratitis

PubMed Central

Lalitha, Prajna; Srinivasan, Muthiah; Manikandan, P.; Bharathi, M. Jayahar; Rajaraman, Revathi; Ravindran, Meenakshi; Cevallos, Vicky; Oldenburg, Catherine E.; Ray, Kathryn J.; Toutain-Kidd, Christine M.; Glidden, David V.; Zegans, Michael E.; McLeod, Stephen D.; Acharya, Nisha R.; Lietman, Thomas M.

2012-01-01

Background. For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. Methods. Data were collected as part of a National Eye Institute–funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. Results. Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040–.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010–.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86–.97; P = .005). Conclusions. In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. Clinical Trials Registration: NCT00324168. PMID:22447793

Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis.

PubMed

Lalitha, Prajna; Srinivasan, Muthiah; Manikandan, P; Bharathi, M Jayahar; Rajaraman, Revathi; Ravindran, Meenakshi; Cevallos, Vicky; Oldenburg, Catherine E; Ray, Kathryn J; Toutain-Kidd, Christine M; Glidden, David V; Zegans, Michael E; McLeod, Stephen D; Acharya, Nisha R; Lietman, Thomas M

2012-05-01

For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005). In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. NCT00324168.

Exopolysaccharide matrix of developed Candida albicans biofilms after exposure to antifungal agents.

PubMed

da Silva, Wander José; Gonçalves, Letícia Machado; Seneviratne, Jayampath; Parahitiyawa, Nipuna; Samaranayake, Lakshman Perera; Del Bel Cury, Altair Antoninha

2012-01-01

This study aimed to evaluate the effects of fluconazole or nystatin exposure on developed Candida albicans biofilms regarding their exopolysaccharide matrix. The minimal inhibitory concentration (MIC) against fluconazole or nystatin was determined for C. albicans reference strain (ATCC 90028). Poly(methlymethacrylate) resin (PMMA) specimens were fabricated according to the manufacturer's instructions and had their surface roughness measured. Biofilms were developed on specimens surfaces for 48 h and after that were exposed during 24 h to fluconazole or nystatin prepared in a medium at MIC, 10 x MIC or 100 x MIC. Metabolic activity was evaluated using an XTT assay. Production of soluble and insoluble exopolysaccharide and intracellular polysaccharides was evaluated by the phenol-sulfuric method. Confocal laser scanning microscope was used to evaluate biofilm architecture and percentage of dead/live cells. Data were analyzed statistically by ANOVA and Tukey's test at 5% significance level. The presence of fluconazole or nystatin at concentrations higher than MIC results in a great reduction of metabolic activity (p<0.001). At MIC or 10 x MIC, fluconazole showed high amounts of intracellular polysaccharides (p<0.05), but did not affect the exopolysaccharide matrix (p>0.05). The exposure to nystatin also did not alter the exopolysaccharide matrix at all the tested concentrations (p>0.05). Biofilm architecture was not affected by either of the antifungal agents (p>0.05). Nystatin promoted higher proportion of dead cells (p<0.05). It may be concluded that fluconazole and nystatin above the MIC concentration reduced the metabolic activity of C. albicans biofilms; however, they were not able to alter the exopolysaccharide matrix and biofilm architecture.

Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1.

PubMed

Mallegol, Julia; Fernandes, Prabhavathi; Melano, Roberto G; Guyard, Cyril

2014-01-01

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis.

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

PubMed Central

Mallegol, Julia; Fernandes, Prabhavathi

2014-01-01

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis. PMID:24277019

The Influence of Reduced Susceptibility to Fluoroquinolones in Salmonella enterica Serovar Typhi on the Clinical Response to Ofloxacin Therapy

PubMed Central

Parry, Christopher M.; Vinh, Ha; Chinh, Nguyen Tran; Wain, John; Campbell, James I.; Hien, Tran Tinh; Farrar, Jeremy J.; Baker, Stephen

2011-01-01

Background Infection with Salmonella enterica serovar Typhi (S. Typhi) with reduced susceptibility to fluoroquinolones has been associated with fluoroquinolone treatment failure. We studied the relationship between ofloxacin treatment response and the ofloxacin minimum inhibitory concentration (MIC) of the infecting isolate. Individual patient data from seven randomised controlled trials of antimicrobial treatment in enteric fever conducted in Vietnam in which ofloxacin was used in at least one of the treatment arms was studied. Data from 540 patients randomised to ofloxacin treatment was analysed to identify an MIC of the infecting organism associated with treatment failure. Principal Findings The proportion of patients failing ofloxacin treatment was significantly higher in patients infected with S. Typhi isolates with an MIC≥0.25 µg/mL compared with those infections with an MIC of ≤0.125 µg/mL (p<0.001). Treatment success was 96% when the ofloxacin MIC was ≤0.125 µg/mL, 73% when the MIC was between 0.25 and 0.50 µg/mL and 53% when the MIC was 1.00 µg/mL. This was despite a longer duration of treatment at a higher dosage in patients infected with isolates with an MIC≥0.25 µg/mL compared with those infections with an MIC of ≤0.125 µg/mL. Significance There is a clear relationship between ofloxacin susceptibility and clinical outcome in ofloxacin treated patients with enteric fever. An ofloxacin MIC of ≥0.25 µg/mL, or the presence of nalidixic acid resistance, can be used to define S. Typhi infections in which the response to ofloxacin may be impaired. PMID:21713025

Is continuous infusion of imipenem always the best choice?

PubMed

Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

2017-03-01

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Antimicrobial activity of tigecycline against recent isolates of respiratory pathogens from Asian countries.

PubMed

Ko, Kwan Soo; Song, Jae-Hoon; Lee, Mi Young; Park, Sulhee; Kwon, Ki Tae; Heo, Sang Taek; Ryu, Seong Yeol; Oh, Won Sup; Peck, Kyong Ran; Lee, Nam Yong

2006-08-01

In vitro activities of tigecycline were compared with 15 other comparator agents against recent clinical isolates of respiratory pathogens (623 Streptococcus pneumoniae, 105 Staphylococcus aureus, 92 Klebsiella pneumoniae, and 84 Haemophilus influenzae isolates) collected from 11 Asian countries. All isolates of S. pneumoniae from Asian countries were susceptible to tigecycline regardless of penicillin susceptibility with MIC90 of

Meta-Analysis

PubMed Central

Kale-Pradhan, Pramodini B.; Mariani, Nicholas P.; Wilhelm, Sheila M.; Johnson, Leonard B.

2015-01-01

Background: Vancomycin is used to treat serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). It is unclear whether MRSA isolates with minimum inhibitory concentration (MIC) 1.5 to 2 µg/mL are successfully treated with vancomycin. Objective: Evaluate vancomycin failure rates in MRSA bacteremia with an MIC <1.5 versus ≥1.5 µg/mL, and MIC ≤1 versus ≥2 µg/mL. Methods: A literature search was conducted using MESH terms vancomycin, MRSA, bacteremia, MIC, treatment and vancomycin failure to identify human studies published in English. All studies of patients with MRSA bacteremia treated with vancomycin were included if they evaluated vancomycin failures, defined as mortality, and reported associated MICs determined by E-test. Study sample size, vancomycin failure rates, and corresponding MIC values were extracted and analyzed using RevMan 5.2.5. Results: Thirteen studies including 2955 patients met all criteria. Twelve studies including 2861 patients evaluated outcomes using an MIC cutoff of 1.5 µg/mL. A total of 413 of 1186 (34.8%) patients with an MIC <1.5 and 531 of 1675 (31.7%) patients with an MIC of ≥1.5 µg/mL experienced treatment failure (odds ratio = 0.72, 95% confidence interval = 0.49-1.04, P = .08). Six studies evaluated 728 patients using the cutoffs of ≤1 and ≥2 µg/mL. A total of 384 patients had isolates with MIC ≤1 µg/mL, 344 had an MIC ≥2 µg/mL. Therapeutic failure occurred in 87 and 102 patients, respectively (odds ratio = 0.61, 95% confidence interval = 0.34-1.10, P = .10). As heterogeneity between the studies was high, a random-effects model was used. Conclusion: Vancomycin MIC may not be an optimal sole indicator of vancomycin treatment failure in MRSA bacteremia.

Susceptibility to antimicrobial agents of Streptococcus suis capsular type 2 strains isolated from pigs.

PubMed

Seol, B; Kelneric, Z; Hajsig, D; Madic, J; Naglic, T

1996-03-01

The minimal inhibitory concentrations (MICs) for thirty-three epidemiologicaly unrelated clinical isolates of Streptococcus suis capsular type 2 were determined in relation to ampicillin, ampicillin-sulbactam, amoxicillin, clavulanate-amoxicillin, penicillin G, cephalexin, gentamicin, streptomycin, erythromycin, tylosin and doxycycline, using the microtitre broth dilution procedure described by the U.S. National Committee for Clinical Laboratory Standards (NCCLS). Gentamicin was the most active compound tested, with an MIC for 90% of the strains tested (MIC(90)) of 0.4 mg/L. Overall, 70% of strains were resistant to doxycycline (MIC(90) > or = 100.0 mg/L), followed by penicillin G (51% of strains) (MIC(90) + or = 100.0 mg/L). Resistance to amoxicillin and ampicillin was 36.4% (MIC(90) 12.5 mg/L) and 33.3% (MIC(90) 50.0 mg/L), respectively. 15.2% of S. suis strains were resistant to streptomycin, tylosin and cephalexin with MIC90 values of 25.0 mg/L, 12.5 mg/L and 25.0 mg/L, respectively. A combination of ampicillin and sulbactam (MIC(90) 6.3 mg/L) and a combination of amoxicillin and clavulanate (MIC(90) 3.1 mg/L) as well as erythromycin (1.6 mg/L) were of the same efficacy, with a total of 9.1% resistant S. suis strains. This high percentage of resistance to doxycycline and penicillin G precludes the use of these antibiotics as empiric therapy of swine diseases.

Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents.

PubMed

Kosowska-Shick, Klaudia; Credito, Kim; Pankuch, Glenn A; Lin, Gengrong; Bozdogan, Bülent; McGhee, Pamela; Dewasse, Bonifacio; Choi, Dong-Rack; Ryu, Jei Man; Appelbaum, Peter C

2006-06-01

DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC(50), 0.016 microg/ml; MIC(90), 0.03 microg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. beta-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 microg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2x MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days.

Potency of marbofloxacin for pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida: Comparison of growth media.

PubMed

Dorey, L; Hobson, S; Lees, P

2017-04-01

Pharmacodynamic properties of marbofloxacin were established for six isolates each of the pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Three in vitro indices of potency were determined; Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Mutant Prevention Concentration (MPC). For MIC determination Clinical Laboratory Standards Institute guidelines were modified in three respects: (1) comparison was made between two growth media, an artificial broth and pig serum; (2) a high inoculum count was used to simulate heavy clinical bacteriological loads; and (3) five overlapping sets of two-fold dilutions were used to improve accuracy of determinations. Similar methods were used for MBC and MPC estimations. MIC and MPC serum:broth ratios for A. pleuropneumoniae were 0.79:1 and 0.99:1, respectively, and corresponding values for P. multocida were 1.12:1 and 1.32:1. Serum protein binding of marbofloxacin was 49%, so that fraction unbound (fu) serum MIC values were significantly lower than those predicted by correction for protein binding; fu serum:broth MIC ratios were 0.40:1 (A. pleuropneumoniae) and 0.50:1 (P. multocida). For broth, MPC:MIC ratios were 13.7:1 (A. pleuropneumoniae) and 14.2:1 (P. multocida). Corresponding ratios for serum were similar, 17.2:1 and 18.8:1, respectively. It is suggested that, for dose prediction purposes, serum data might be preferable to potency indices measured in broths. Copyright © 2016 Elsevier Ltd. All rights reserved.

In Vitro Antimicrobial Susceptibility Testing of Helicobacter felis, H. bizzozeronii, and H. salomonis

PubMed Central

Van den Bulck, K.; Decostere, A.; Gruntar, I.; Baele, M.; Krt, B.; Ducatelle, R.; Haesebrouck, F.

2005-01-01

The susceptibilities of Helicobacter felis (15 strains), H. bizzozeronii (7 strains), and H. salomonis (3 strains) to 10 antimicrobial agents were investigated by determination of the MIC using the agar dilution method. No consistent differences were noticed between the different Helicobacter species, which were all highly susceptible to ampicillin, clarithromycin, tetracycline, tylosin, enrofloxacin, gentamicin, and neomycin, as demonstrated by low MICs. Higher MICs were obtained for lincomycin (up to 8 μg/ml) and spectinomycin (up to 4 μg/ml). Two H. felis strains showed a MIC of 16 μg/ml for metronidazole, suggesting acquired resistance to this antimicrobial agent. PMID:15980383

Antimicrobial susceptibility pattern of clinical isolates of Burkholderia pseudomallei in Bangladesh.

PubMed

Dutta, Subarna; Haq, Sabah; Hasan, Mohammad Rokibul; Haq, Jalaluddin Ashraful

2017-07-20

Melioidosis an infectious disease, caused by a Gram negative bacterium called Burkholderia pseudomallei, is endemic in Bangladesh. This organism is sensitive to limited number of antimicrobial agents and need prolonged treatment. There is no comprehensive data on the antimicrobial susceptibility profile of B. pseudomallei isolated in Bangladesh over last several years. The present study aimed to determine the antimicrobial susceptibility pattern of B. pseudomallei isolated in a tertiary care hospital of Dhaka city from 2009 to 2015. All B. pseudomallei isolated from melioidosis patients over a period of 7 years (2009-2015) in the Department of Microbiology of a 725-bed tertiary care referral hospital in Dhaka city, Bangladesh were included in the study. B. pseudomallei was identified by Gram stain, culture, specific biochemical tests, serology and PCR using specific primers constructed from 16s rRNA region of B. pseudomallei. Antimicrobial susceptibility to specific agents was determined by disk diffusion and minimum inhibitory concentration methods. A total of 20 isolates of B. pseudomallei which were isolated from patients coming from different geographic locations of Bangladesh were included in the study. All the isolates were uniformly sensitive (100%) to ceftazidime, imipenem, piperacillin-tazobactam, amoxicillin-clavulanic acid and tetracycline by both disk diffusion and MIC methods. Two strains were resistant to trimethoprim-sulfamethoxazole by disk diffusion method but were sensitive by MIC method. The MIC 50 and MIC 90 values of the above antimicrobial agents were almost similar. All the isolates were resistant to amikacin by both MIC and disk diffusion methods. The results of the study suggest that B. pseudomallei prevalent in Bangladesh were still susceptible to all recommended antimicrobial agents used for the treatment of melioidosis. However, regular monitoring is needed to detect any emergence of resistance and shifting of MIC 50 and MIC 90 values.

An investigation of vancomycin minimum inhibitory concentration creep among methicillin-resistant Staphylococcus aureus strains isolated from pediatric patients and healthy children in Northern Taiwan.

PubMed

Chang, Chia-Ning; Lo, Wen-Tsung; Chan, Ming-Chin; Yu, Ching-Mei; Wang, Chih-Chien

2017-06-01

The phenomenon of vancomycin minimum inhibitory concentration (MIC) creep is an increasingly serious problem in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. In this study, we investigated the vancomycin and daptomycin MIC values of MRSA strains isolated from pediatric patients and MRSA colonized healthy children. Then, we assessed whether there was evidence of clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 μg/mL. We collected clinical MRSA isolates from pediatric patients and from healthy children colonized with MRSA during 2008-2012 at a tertiary medical center in northern Taiwan and obtained vancomycin and daptomycin MIC values using the Etest method. Pulse-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome (SCCmec) typing were used to assess clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 μg/mL. A total 195 MRSA strains were included in this study; 87 were isolated patients with a clinical MRSA infection, and the other 108 strains from nasally colonized healthy children. Vancomycin MIC≥1.5 μg/mL was seen in more clinical isolates (60/87, 69%) than colonized isolates (32/108, 29.6%), p < 0.001. The PFGE typing of both strains revealed multiple pulsotypes. Vancomycin MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains. Great diversity of PFGE typing was in both strains collected. There was no association between the clinical and colonized MRSA isolates with vancomycin MIC creep. Copyright © 2016. Published by Elsevier B.V.

Wild-type MIC distributions for aminoglycoside and cyclic polypeptide antibiotics used for treatment of Mycobacterium tuberculosis infections.

PubMed

Juréen, P; Angeby, K; Sturegård, E; Chryssanthou, E; Giske, C G; Werngren, J; Nordvall, M; Johansson, A; Kahlmeter, G; Hoffner, S; Schön, T

2010-05-01

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed +/-1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis.

Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections▿

PubMed Central

Juréen, P.; Ängeby, K.; Sturegård, E.; Chryssanthou, E.; Giske, C. G.; Werngren, J.; Nordvall, M.; Johansson, A.; Kahlmeter, G.; Hoffner, S.; Schön, T.

2010-01-01

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed ±1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis. PMID:20237102

In vitro combined effect of co-amoxiclav concentrations achievable in serum after a 2000/125 mg oral dose, and polymorphonuclear neutrophils against strains of Streptococcus pneumoniae exhibiting decreased susceptibility to amoxicillin.

PubMed

Amores, Raquel; Alou, Luis; Giménez, María José; Sevillano, David; Gómez-Lus, María Luisa; Aguilar, Lorenzo; Prieto, José

2004-07-01

The in vitro effect that the presence of components of non-specific immunity (serum plus polymorphonuclear neutrophils) has on the bactericidal activity of co-amoxiclav was explored against Streptococcus pneumoniae strains exhibiting an amoxicillin MIC > or =4 mg/L. Eight penicillin-resistant clinical isolates non-susceptible to co-amoxiclav with MICs of 4 (two strains), 8 (four strains) and 16 mg/L (two strains) were used. Values of MBC were identical to MIC values in all cases. Time-kill curves were performed with co-amoxiclav concentrations achievable in serum after a single oral dose administration of the new 2000/125 mg sustained-release formulation. Results were expressed as percentage of reduction of initial inocula after 3 h incubation. Control curves showed growth with no reduction of initial inocula. Against strains with MIC of 4 and 8 mg/L, the results obtained with the antibiotic alone or with the presence of factors of non-specific immunity were similar, with a weak combined effect due to the intrinsic activity of co-amoxiclav (reductions of initial inocula ranging from 70 to 99.16%). Against strains with MIC of 16 mg/L, the addition of PMN in the presence of serum increased the reduction of bacterial load provided by the aminopenicillin, even at sub-inhibitory concentrations (25.8% versus 51.1% at 0.5 x MIC concentration--8/0.5 mg/L). This combined activity against strains with an amoxicillin MIC of 16 mg/L which decreased the bacterial load may be important in preventing bacterial proliferation within the host and the transmission of resistant clones to others.

[Comparison of four MICS intraocular lenses regarding their rates of neodymium:YAG laser capsulotomy].

PubMed

Spyridaki, M; Höh, H

2010-03-01

The aim of this study was to evaluate the incidence of posterior capsule opacification up to 50 months following 1.7-mm bimanual MICS-cataract surgery. Bimanual MICS cataract surgery was performed in 197 eyes (135 patients) via two 1.7-mm corneal incisions. Four MICS acrylic foldable IOLs were implanted: AcriSmart 48S-5, n = 54 (Acritec GmbH, Hennigsdorf, now AT.Smart 48S Carl-Zeiss-Meditec, AG, Jena, Germany), ThinLens UltraChoice 1.0, n = 53 (Technomed GmbH, Baesweiler, Germany), AcriFlex 46, n = 41 und AcriFlex 48 CSE, n = 7 (Acrimed GmbH, Berlin, now: Lentis L-303, Oculentis GmbH, Berlin, Germany) and CareFlex, n = 43 (w2o Medizintechnik AG, Bruchsal, Germany). Statistical analysis was performed using the Kaplan-Meier technique. High levels of completeness of follow-up rates were: ThinLens 96%, CareFlex 100%, AcriSmart 93%, AcriFlex 92%. The capsulotomy rate was 43.13% for ThinLens within a mean/max. follow-up period of 801/1131 days, 34.88% for CareFlex (565/872 days), 40% for AcriSmart (988/1506 days) and 15.91% for AcriFlex (728/975 days). By limiting the follow-up period to a comparable maximum of 850 days for all four IOLs, our capsulotomy rates were as follows: ThinLens 33.33%, CareFlex 32.56 %, AcriSmart 20.0% and AcriFlex 11.36%. MICS IOLs have higher capsulotomy rates than hydrophobic acrylic lenses and sharp-edged silicone lenses. In literature comparisons MICS-IOLs do not exceed the variance levels of capsulotomy rates of PMMA, hydrophilic acrylic and silicone lenses without sharp edges. Cases of decentration or luxation of MICS-IOLs following Neodym:YAG laser capsulotomy were not detected. Capsulotomy frequency with the CareFlex was statistically significantly higher in comparison to the AcriSmart (Log Rank Mantel Cox Test, p = 0.007) and AcriFlex (log rank Mantel Cox test, p = 0.002). Capsulotomy rates observed varied for the four MICS-IOL-types tested. The posterior capsule opacification frequency of the two best MICS-IOLs (AcriFlex, AcriSmart) did not exceed the higher variance levels of posterior capsule opacification rates of the round-edged "conventional" non-MICS IOLs of PMMA, silicone or hydrophilic acryl material. Sharp-edged silicone or hydrophobic acrylic "conventional" lenses have shown lower posterior capsule opacification rates. Georg Thieme Verlag KG Stuttgart, New York.

Analysis of Triclosan-Selected Salmonella enterica Mutants of Eight Serovars Revealed Increased Aminoglycoside Susceptibility and Reduced Growth Rates

PubMed Central

Rensch, Ulrike; Klein, Guenter; Kehrenberg, Corinna

2013-01-01

The biocide triclosan (TRC) is used in a wide range of household, personal care, veterinary, industrial and medical products to control microbial growth. This extended use raises concerns about a possible association between the application of triclosan and the development of antibiotic resistance. In the present study we determined triclosan mutant prevention concentrations (MPC) for Salmonella enterica isolates of eight serovars and investigated selected mutants for their mechanisms mediating decreased susceptibility to triclosan. MPCTRC values were 8 - 64-fold higher than MIC values and ranged between 1 - 16 µg/ml. The frequencies at which mutants were selected varied between 1.3 x 10-10 - 9.9 x 10-11. Even if MIC values of mutants decreased by 3-7 dilution steps in the presence of the efflux pump inhibitor Phe-Arg-β-naphtylamide, only minor changes were observed in the expression of genes encoding efflux components or regulators, indicating that neither the major multidrug efflux pump AcrAB-TolC nor AcrEF are up-regulated in triclosan-selected mutants. Nucleotide sequence comparisons confirmed the absence of alterations in the regulatory regions acrRA, soxRS, marORAB, acrSE and ramRA of selected mutants. Single bp and deduced Gly93→Val amino acid exchanges were present in fabI, the target gene of triclosan, starting from a concentration of 1 µg/ml TRC used for MPC determinations. The fabI genes were up to 12.4-fold up-regulated. Complementation experiments confirmed the contribution of Gly93→Val exchanges and fabI overexpression to decreased triclosan susceptibility. MIC values of mutants compared to parent strains were even equal or resulted in a more susceptible phenotype (1-2 dilution steps) for the aminoglycoside antibiotics kanamycin and gentamicin as well as for the biocide chlorhexidine. Growth rates of selected mutants were significantly lower and hence, might partly explain the rare occurrence of Salmonella field isolates exhibiting decreased susceptibility to triclosan. PMID:24205194

Effects of lead and cadmium nitrate on biomass and substrate utilization pattern of soil microbial communities.

PubMed

Muhammad, Akmal; Xu, Jianming; Li, Zhaojun; Wang, Haizhen; Yao, Huaiying

2005-07-01

A study was conducted to evaluate the effects of different concentrations of lead (Pb) and cadmium (Cd) applied as their nitrates on soil microbial biomass carbon (C(mic)) and nitrogen (N(mic)), and substrate utilization pattern of soil microbial communities. The C(mic) and N(mic) contents were determined at 0, 14, 28, 42 and 56 days after heavy metal application (DAA). The results showed a significant decline in the C(mic) for all Pb and Cd amended soils from the start to 28 DAA. From 28 to 56 DAA, C(mic) contents changed non-significantly for all other treatments except for 600 mgkg(-1) Pb and 100 mgkg(-1) Cd in which it declined significantly from 42 to 56 DAA. The N(mic) contents also decreased significantly from start to 28 DAA for all other Pb and Cd treatments except for 200 mgkg(-1) Pb which did not show significant difference from the control. Control and 200 mgkg(-1) Pb had significantly lower soil microbial biomass C:N ratio as compared with other Pb treatments from 14 to 42 DAA, however at 56 DAA, only 1000 mgkg(-1) Pb showed significantly higher C:N ratio compared with other treatments. No significant difference in C:N ratio for all Cd treated soils was seen from start to 28 DAA, however from 42 to 56 DAA, 100 mgkg(-1) Pb showed significantly higher C:N ratio compared with other treatments. On 56 DAA, substrate utilization pattern of soil microbial communities was determined by inoculating Biolog ECO plates. The results indicated that Pb and Cd addition inhibited the functional activity of soil microbial communities as indicated by the intensity of average well color development (AWCD) during 168 h of incubation. Multivariate analysis of sole carbon source utilization pattern demonstrated that higher levels of heavy metal application had significantly affected soil microbial community structure.

In Vitro Activities of Various Antimicrobials Alone and in Combination with Tigecycline against Carbapenem-Intermediate or -Resistant Acinetobacter baumannii▿

PubMed Central

Scheetz, Marc H.; Qi, Chao; Warren, John R.; Postelnick, Michael J.; Zembower, Teresa; Obias, Arlene; Noskin, Gary A.

2007-01-01

The activities of tigecycline alone and in combination with other antimicrobials are not well defined for carbapenem-intermediate or -resistant Acinetobacter baumannii (CIRA). Pharmacodynamic activity is even less well defined when clinically achievable serum concentrations are considered. Antimicrobial susceptibility testing of clinical CIRA isolates from 2001 to 2005 was performed by broth or agar dilution, as appropriate. Tigecycline concentrations were serially increased in time-kill studies with a representative of the most prevalent carbapenem-resistant clone (strain AA557; imipenem MIC, 64 mg/liter). The in vitro susceptibility of the strain was tested by time-kill studies in duplicate against the average free serum steady-state concentrations of tigecycline alone and in combination with various antimicrobials. Ninety-three CIRA isolates were tested and were found to have the following antimicrobial susceptibility profiles: tigecycline, MIC50 of 1 mg/liter and MIC90 of 2 mg/liter; minocycline, MIC50 of 0.5 mg/liter and MIC90 of 8 mg/liter; doxycycline, MIC50 of 2 mg/liter and MIC90 of ≥32 mg/liter; ampicillin-sulbactam, MIC50 of 48 mg/liter and MIC90 of 96 mg/liter; ciprofloxacin, MIC50 of ≥16 mg/liter and MIC90 of ≥16 mg/liter; rifampin, MIC50 of 4 mg/liter and MIC90 of 8 mg/liter; polymyxin B, MIC50 of 1 mg/liter and MIC90 of 1 mg/liter; amikacin, MIC50 of 32 mg/liter and MIC90 of ≥32 mg/liter; meropenem, MIC50 of 16 mg/liter and MIC90 of ≥128 mg/liter; and imipenem, MIC50 of 4 mg/liter and MIC90 of 64 mg/liter. Among the tetracyclines, the isolates were more susceptible to tigecycline than minocycline and doxycycline, according to FDA breakpoints (95%, 88%, and 71% of the isolates were susceptible to tigecycline, minocycline, and doxycycline, respectively). Concentration escalation studies with tigecycline revealed a maximal killing effect near the MIC, with no additional extent or rate of killing at concentrations 2× to 4× the MIC for tigecycline. Time-kill studies demonstrated indifference for tigecycline in combination with the antimicrobials tested. Polymyxin B, minocycline, and tigecycline are the most active antimicrobials in vitro against CIRA. Concentration escalation studies demonstrate that tigecycline may need to approach concentrations higher than those currently achieved in the bloodstream to adequately treat CIRA bloodstream infections. Future studies should evaluate these findings in vivo. PMID:17307973

Susceptibility profile and epidemiological cut-off values of Cryptococcus neoformans species complex from Argentina.

PubMed

Córdoba, Susana; Isla, Maria G; Szusz, Wanda; Vivot, Walter; Altamirano, Rodrigo; Davel, Graciela

2016-06-01

Epidemiological cut-off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild-type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC50 , MIC90 and ECV for each of these drugs were calculated. The highest ECV, which included ≥95% of the WT population modelled, was observed for flucytosine and fluconazole (32 μg ml(-1) each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 μg ml(-1) respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested. © 2016 Blackwell Verlag GmbH.

Efficacy of taurolidine against periodontopathic species--an in vitro study.

PubMed

Eick, Sigrun; Radakovic, Sabrina; Pfister, Wolfgang; Nietzsche, Sandor; Sculean, Anton

2012-06-01

The antimicrobial effect of taurolidine was tested against periodontopathic species in comparison to chlorhexidine digluconate in the presence or absence of serum. Minimal inhibitory concentrations (MIC), microbiocidal concentrations (MBC), as well as killing were determined against 32 different microbial strains including 3 Porphyromonas gingivalis, 3 Aggregatibacter actinomycetemcomitans, and 15 potentially superinfecting species with and without 25% v/v human serum. The MIC(50) of taurolidine against the tested microbial strains was 0.025% and the MIC(90) 0.05%. The respective values for the MBCs were 0.05% and 0.1%. Addition of 25% serum (heat-inactivated) did not change the MIC and MBC values of taurolidine. In contrast, MICs and MBCs of chlorhexidine (CHX) increased by two steps after addition of serum. Taurolidine killed microorganisms in a concentration and time-dependent manner, the killing rate of 1.6% taurolidine was 99.08% ± 2.27% in mean after 2 h. Again, killing activity of taurolidine was not affected if serum was added, whereas addition of inactivated serum clearly reduced the killing rate of all selected bacterial strains by CHX. Therefore, taurolidine possesses antimicrobial properties which are not reduced in the presence of serum as a main component in gingival crevicular fluid and wound fluid. Taurolidine may have potential as an antimicrobial agent in non-surgical and surgical periodontal treatment.

Late Pleistocene Sea level on the New Jersey Margin: Implications to eustasy and deep-sea temperature

USGS Publications Warehouse

Wright, J.D.; Sheridan, R.E.; Miller, K.G.; Uptegrove, J.; Cramer, B.S.; Browning, J.V.

2009-01-01

We assembled and dated a late Pleistocene sea-level record based on sequence stratigraphy from the New Jersey margin and compared it with published records from fossil uplifted coral reefs in New Guinea, Barbados, and Araki Island, as well as a composite sea-level estimate from scaling of Red Sea isotopic values. Radiocarbon dates, amino acid racemization data, and superposition constrain the ages of large (20-80??m) sea-level falls from New Jersey that correlate with Marine Isotope Chrons (MIC) 2, 3b, 4, 5b, and 6 (the past 130??kyr). The sea-level records for MIC 1, 2, 4, 5e, and 6 are similar to those reported from New Guinea, Barbados, Araki, and the Red Sea; some differences exist among records for MIC 3. Our record consistently provides the shallowest sea level estimates for MIC3 (??? 25-60??m below present); it agrees most closely with the New Guinea record of Chappell (2002; ??? 35-70??m), but contrasts with deeper estimates provided by Araki (??? 85-95??m) and the Red Sea (50-90??m). Comparison of eustatic estimates with benthic foraminiferal ??18O records shows that the deep sea cooled ??? 2.5????C between MIC 5e and 5d (??? 120-110??ka) and that near freezing conditions persisted until Termination 1a (14-15??ka). Sea-level variations between MIC 5b and 2 (ca. 90-20??ka) follow a well-accepted 0.1???/10??m linear variation predicted by ice-growth effects on foraminiferal ??18O values. The pattern of deep-sea cooling follows a previously established hysteresis loop between two stable modes of operation. Cold, near freezing deep-water conditions characterize most of the past 130??kyr punctuated only by two warm intervals (the Holocene/MIC 1 and MIC 5e). We link these variations to changes in Northern Component Water (NCW). ?? 2009 Elsevier B.V. All rights reserved.

Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.

PubMed

Ehmann, Lisa; Zoller, Michael; Minichmayr, Iris K; Scharf, Christina; Maier, Barbara; Schmitt, Maximilian V; Hartung, Niklas; Huisinga, Wilhelm; Vogeser, Michael; Frey, Lorenz; Zander, Johannes; Kloft, Charlotte

2017-10-21

Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed. Clinicaltrials.gov, NCT01793012 . Registered on 24 January 2013.

Antibacterial activities of the methanol extract, fractions and compounds from Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae).

PubMed

Voukeng, Igor K; Nganou, Blaise K; Sandjo, Louis P; Celik, Ilhami; Beng, Veronique P; Tane, Pierre; Kuete, Victor

2017-01-07

Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae) is used in Cameroonian folk medicine to treat several ailments including bacterial-related diseases such as skin infections. In this study, the methanol extract from the leaves (EDL), fractions (EDLa-d), sub-fractions EDLc1-7 and EDLc31-35 as well as isolated compounds were tested for their antimicrobial activities against a panel of Gram-negative and Gram-positive bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the leaves extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Phytochemical investigation lead to the isolation of a mixture (1:3) of stigmasterol and β-sitosterol (1 + 2), euphol (3), sitosterol-O-β- D -xylopyranoside (4), 3,3',4'-tri-O-methylellagic acid (5), a mixture (1:1) of afzelin and quercetin-3-O-β- D -xylopyranoside (6 + 7), 3,3',4'-tri-O-methylellagic acid 4-O-β- D -glucopyranoside (8), ellagic acid-4-O-β-xylopyranoside-3,3',4'-trimethyl ether (9) from EDLc. Crude extract and fractions displayed selective activities with MIC values ranged from 32 to 1024 μg/mL for EDL against 84.9% of the 33 tested bacteria, 93.9% for EDLc, 69.7% for EDLb, 33.4% for EDLa and 0.03% for EDLd. MIC values ranged from 16 to 1024 μg/mL were obtained with EDLc3 and EDLc4 on all tested bacteria meanwhile other sub-fractions displayed selective activities. MIC value of 32 μg/mL was obtained with fractions EDLa against Escherichia coli AG100, EDLc against Enterobacer aerogenes ATCC13048 and EA298. For sub-fractions obtained from EDLc, the lowest MIC value of 16 μg/mL was recorded with EDLc3 against Staphylococcus aureus MRSA11. A corresponding value of 8 μg/mL against Providencia stuartii NAE16 was recorded with EDLc33 obtained from further fractionation of EDLc3. EDLc3 had MIC values below 100 μg/mL against all tested bacteria. Compound 5 as well as the mixture (1:1) of 6 and 7 inhibited the growth of all the tested bacteria with MICs ranged from 64 to 256 μg/mL. Elaeophorbia drupifera is a potential source of phytomedicine to tackle MDR bacteria. Sub-fraction EDLc3 was more active than all isolated compounds and deserves further investigations to develop natural drug to combat Gram-negative, Gram-positive bacteria and otherwise MDR phenotypes.

Antimicrobial Susceptibility of Flavobacterium psychrophilum from Chilean Salmon Farms and Their Epidemiological Cut-Off Values Using Agar Dilution and Disk Diffusion Methods.

PubMed

Miranda, Claudio D; Smith, Peter; Rojas, Rodrigo; Contreras-Lynch, Sergio; Vega, J M Alonso

2016-01-01

Flavobacterium psychrophilum is the most important bacterial pathogen for freshwater farmed salmonids in Chile. The aims of this study were to determine the susceptibility to antimicrobials used in fish farming of Chilean isolates and to calculate their epidemiological cut-off (CO WT ) values. A number of 125 Chilean isolates of F. psychrophilum were isolated from reared salmonids presenting clinical symptoms indicative of flavobacteriosis and their identities were confirmed by 16S rRNA polymerase chain reaction. Susceptibility to antibacterials was tested on diluted Mueller-Hinton by using an agar dilution MIC method and a disk diffusion method. The CO WT values calculated by Normalized Resistance Interpretation (NRI) analysis allow isolates to be categorized either as wild-type fully susceptible (WT) or as manifesting reduced susceptibility (NWT). When MIC data was used, NRI analysis calculated a CO WT of ≤0.125, ≤2, and ≤0.5 μg mL -1 for amoxicillin, florfenicol, and oxytetracycline, respectively. For the quinolones, the CO WT were ≤1, ≤0.5, and ≤0.125 μg mL -1 for oxolinic acid, flumequine, and enrofloxacin, respectively. The disk diffusion data sets obtained in this work were extremely diverse and were spread over a wide range. For the quinolones there was a close agreement between the frequencies of NWT isolates calculated using MIC and disk data. For oxolinic acid, flumequine, and enrofloxacin the frequencies were 45, 39, and 38% using MIC data, and 42, 41, and 44%, when disk data were used. There was less agreement with the other antimicrobials, because NWT frequencies obtained using MIC and disk data, respectively, were 24 and 10% for amoxicillin, 8 and 2% for florfenicol, and 70 and 64% for oxytetracycline. Considering that the MIC data was more precise than the disk diffusion data, MIC determination would be the preferred method for susceptibility testing for this species and the NWT frequencies derived from the MIC data sets should be considered as the more authoritative. Despite the high frequency of isolates showing full susceptibility to florfenicol, the significant frequencies of isolates exhibiting reduced susceptibility to oxytetracycline and quinolones may result in treatment failures when these agents are used.

In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from United States Hospitals and Comparative Activity of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes.

PubMed

Castanheira, Mariana; Davis, Andrew P; Mendes, Rodrigo E; Serio, Alisa W; Krause, Kevin M; Flamm, Robert K

2018-06-04

Plazomicin and comparators agents were tested using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 United States hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC 50/90 , 0.5/2 μg/ml) inhibited 99.2% of 4,362 Enterobacteriaceae at ≤4 μg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, applying CLSI breakpoints. The activity of plazomicin was similar among Enterobacteriaceae species with MIC 50 values ranging from 0.25 to 1 μg/ml, with exception of Proteus mirabilis and indole-positive Proteaee that displayed MIC 50 values of 2 μg/ml. Against 97 carbapenem-resistant Enterobacteriaceae (CRE) that included 87 isolates carrying bla KPC , plazomicin inhibited all but 1 isolate at ≤2 μg/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5/95.5% of the gentamicin-resistant, 96.9/96.5% of the tobramycin-resistant and 64.3/90.0% of the amikacin-resistant isolates using CLSI/EUCAST breakpoints. The activity of plazomicin against Pseudomonas aeruginosa (MIC 50/90 , 4/16 μg/ml) and Acinetobacter spp. (MIC 50/90 , 2/16 μg/ml) isolates was similar. Plazomicin was active against coagulase-negative staphylococci (MIC 50/90 , 0.12/0.5 μg/ml) and Staphylococcus aureus (MIC 50/90 , 0.5/0.5 μg/ml), but had limited activity against Enterococcus spp. (MIC 50/90 , 16/64 μg/ml) and Streptococcus pneumoniae (MIC 50/90 , 32/64 μg/ml). Plazomicin activity against the Enterobacteriaceae tested, including CRE and isolates carrying bla KPC from U.S. hospitals, support the development plan for plazomicin to treat serious infections caused by resistant Enterobacteriaceae in patients with limited treatment options. Copyright © 2018 American Society for Microbiology.

In Vitro Activity of Ertapenem versus Ceftriaxone against Neisseria gonorrhoeae Isolates with Highly Diverse Ceftriaxone MIC Values and Effects of Ceftriaxone Resistance Determinants: Ertapenem for Treatment of Gonorrhea?

PubMed Central

Golparian, Daniel; Limnios, Athena; Whiley, David; Ohnishi, Makoto; Lahra, Monica M.; Tapsall, John W.

2012-01-01

Clinical resistance to the currently recommended extended-spectrum cephalosporins (ESCs), the last remaining treatment options for gonorrhea, is being reported. Gonorrhea may become untreatable, and new treatment options are crucial. We investigated the in vitro activity of ertapenem, relative to ceftriaxone, against N. gonorrhoeae isolates and the effects of ESC resistance determinants on ertapenem. MICs were determined using agar dilution technique or Etest for international reference strains (n = 17) and clinical N. gonorrhoeae isolates (n = 257), which included the two extensively drug-resistant (XDR) strains H041 and F89 and additional isolates with high ESC MICs, clinical ESC resistance, and other types of clinical high-level and multidrug resistance (MDR). Genetic resistance determinants for ESCs (penA, mtrR, and penB) were sequenced. In general, the MICs of ertapenem (MIC50 = 0.032 μg/ml; MIC90 = 0.064 μg/ml) paralleled those of ceftriaxone (MIC50 = 0.032 μg/ml; MIC90 = 0.125 μg/ml). The ESC resistance determinants mainly increased the ertapenem MIC and ceftriaxone MIC at similar levels. However, the MIC ranges for ertapenem (0.002 to 0.125 μg/ml) and ceftriaxone (<0.002 to 4 μg/ml) differed, and the four (1.5%) ceftriaxone-resistant isolates (MIC = 0.5 to 4 μg/ml) had ertapenem MICs of 0.016 to 0.064 μg/ml. Accordingly, ertapenem had in vitro advantages over ceftriaxone for isolates with ceftriaxone resistance. These in vitro results suggest that ertapenem might be an effective treatment option for gonorrhea, particularly for the currently identified ESC-resistant cases and possibly in a dual antimicrobial therapy regimen. However, further knowledge regarding the genetic determinants (and their evolution) conferring resistance to both antimicrobials, and clear correlates between genetic and phenotypic laboratory parameters and clinical treatment outcomes, is essential. PMID:22547617

Vancomycin tolerance in enterococci.

PubMed

Saribas, Suat; Bagdatli, Yasar

2004-11-01

Tolerance can be defined as the ability of bacteria to grow in the presence of high concentrations of bactericide antimicrobics, so that the killing action of the drug is avoided but the minimal inhibitory concentration (MIC) remains the same. We investigated vancomycin tolerance in the Enterococcus faecium and Enterococcus faecalis strains isolated from different clinical specimens. Vancomycin was obtained from Sigma Chemical Co. We studied 100 enterococci strains. Fifty-six and 44 of Enterococcus strains were idendified as E. feacalis and E. faecium, respectively. To determine MICs and minimal bactericidal concentration (MBC), we inoculated strains from an overnight agar culture to Muller-Hinton broth and incubated them for 4-6 h at 37 degrees C with shaking to obtain a logarithmic phase culture. The inoculum was controlled by performing a colony count for each test. We determined MBC values and MBC/MIC ratios to study tolerance to vancomycin. Vancomycin tolerance was defined as a high MBC value and an MBC/MIC ratio > or =32. Fifty-six and 44 of the Enterococcus strains were identified as E. faecium and E. faecalis, respectively. Thirty-one E. faecium and 48 E. faecalis were found to be susceptible to vancomycin and these susceptible strains were included in this study. The MICs of susceptible strains ranged from < or =1 to 4 mg/l, the MBCs were > or =512 mg/l. Tolerance was detected in all E. faecalis and E. faecium strains. The standard E. faecalis 21913 strain also exhibited tolerance according to the high MBC value and the MBC/MIC ratio. We defined the tolerant strains as having no bactericidal effect and MBC/MIC > or =32. We found that a 100% tolerance was present in susceptible strains. One of the hypotheses for tolerance is that tolerant cells fail to mobilize or create the autolysins needed for enlargement and division. Our data suggests that tolerance may compromise glycopeptide therapy of serious enterococci infections. To add an aminoglycoside to the glycopeptide therapy unless MBCs are unavailable can be useful in the effective treatment of serious Enterococcus infections.

The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey

PubMed Central

Tan, Hern Tze; Rahman, Rosliza Abdul; Gan, Siew Hua; Halim, Ahmad Sukari; Hassan, Siti Asma'; Sulaiman, Siti Amrah; BS, Kirnpal-Kaur

2009-01-01

Background Antibiotic resistance of bacteria is on the rise, thus the discovery of alternative therapeutic agents is urgently needed. Honey possesses therapeutic potential, including wound healing properties and antimicrobial activity. Although the antimicrobial activity of honey has been effectively established against an extensive spectrum of microorganisms, it differs depending on the type of honey. To date, no extensive studies of the antibacterial properties of tualang (Koompassia excelsa) honey on wound and enteric microorganisms have been conducted. The objectives of this study were to conduct such studies and to compare the antibacterial activity of tualang honey with that of manuka honey. Methods Using a broth dilution method, the antibacterial activity of tualang honey against 13 wound and enteric microorganisms was determined; manuka honey was used as the control. Different concentrations of honey [6.25-25% (w/v)] were tested against each type of microorganism. Briefly, two-fold dilutions of honey solutions were tested to determine the minimum inhibitory concentration (MIC) against each type of microorganism, followed by more assays within a narrower dilution range to obtain more precise MIC values. MICs were determined by both visual inspection and spectrophotometric assay at 620 nm. Minimum bactericidal concentration (MBC) also was determined by culturing on blood agar plates. Results By visual inspection, the MICs of tualang honey ranged from 8.75% to 25% compared to manuka honey (8.75-20%). Spectrophotometric readings of at least 95% inhibition yielded MIC values ranging between 10% and 25% for both types of honey. The lowest MBC for tualang honey was 20%, whereas that for manuka honey was 11.25% for the microorganisms tested. The lowest MIC value (8.75%) for both types of honey was against Stenotrophomonas maltophilia. Tualang honey had a lower MIC (11.25%) against Acinetobacter baumannii compared to manuka honey (12.5%). Conclusion Tualang honey exhibited variable activities against different microorganisms, but they were within the same range as those for manuka honey. This result suggests that tualang honey could potentially be used as an alternative therapeutic agent against certain microorganisms, particularly A. baumannii and S. maltophilia. PMID:19754926

Antipneumococcal Activity of DW-224a, a New Quinolone, Compared to Those of Eight Other Agents

PubMed Central

Kosowska-Shick, Klaudia; Credito, Kim; Pankuch, Glenn A.; Lin, Gengrong; Bozdogan, Bülent; McGhee, Pamela; Dewasse, Bonifacio; Choi, Dong-Rack; Ryu, Jei Man; Appelbaum, Peter C.

2006-01-01

DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC50, 0.016 μg/ml; MIC90, 0.03 μg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. β-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 μg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2× MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days. PMID:16723567

Antibacterial activity of Pinus elliottii against anaerobic bacteria present in primary endodontic infections.

PubMed

Caetano da Silva, Sandro Donizete; Mendes de Souza, Maria Gorete; Oliveira Cardoso, Miguel Jorge; da Silva Moraes, Thais; Ambrósio, Sérgio Ricardo; Sola Veneziani, Rodrigo Cássio; Martins, Carlos Henrique G

2014-12-01

Endodontic infections have a polymicrobial nature, but anaerobic bacteria prevail among the infectious microbes. Considering that it is easy to eliminate planktonic bacteria, biofilm-forming bacteria still challenge clinicians during the fight against endodontic diseases. The chemical constituents of the oleoresin of Pinus elliottii, a plant belonging to the family Pinaceae, stand out in the search for biologically active compounds based on natural products with potential application in the treatment of endodontic infections. Indeed, plant oleoresins are an abundant natural source of diterpenes that display significant and well-defined biological activities as well as potential antimicrobial action. In this context, this study aimed to (1) evaluate the in vitro antibacterial activity of the oleoresin, fractions, and subfractions of P. elliottii as well as the action of dehydroabietic acid against 11 anaerobic bacteria that cause endodontic infection in both their planktonic and biofilm forms and (2) assess the in vitro antibiofilm activity of dehydroabietic acid against the same group of bacteria. The broth microdilution technique helped to determine the minimum inhibitory concentration (MIC) of the oleoresin and fractions. This same technique aided determination of the MIC values of nine subfractions of Fraction 1, the most active fraction. The MIC, minimum bactericidal concentration, and antibiofilm activity of dehydroabietic acid against the tested anaerobic bacteria were also examined. The oleoresin and fractions, especially fraction PE1, afforded promising MIC values, which ranged from 0.4 to 50 μg/mL. Concerning the nine evaluated subfractions, PE1.3 and PE1.4 furnished the most noteworthy MIC values, between 6.2 and 100 μg/mL. Dehydroabietic acid displayed antibacterial activity, with MIC values lying from 6.2 to 50 μg/mL, as well as bactericidal effect for all the investigated bacteria, except for Prevotella nigrescens. Assessment of the antibiofilm activity revealed significant results--MICB50 lay between 7.8 and 62.5 μg/mL, and dehydroabietic acid prevented all the evaluated bacteria from forming a biofilm. Hence, the chemical constituents of P. elliottii are promising biomolecules to develop novel therapeutic strategies to fight against endodontic infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tolerance response of multidrug-resistant Salmonella enterica strains to habituation to Origanum vulgare L. essential oil

PubMed Central

Monte, Daniel F. M.; Tavares, Adassa G.; Albuquerque, Allan R.; Sampaio, Fábio C.; Oliveira, Tereza C. R. M.; Franco, Octavio L.; Souza, Evandro L.; Magnani, Marciane

2014-01-01

Multidrug-resistant Salmonella enterica isolates from human outbreaks or from poultry origin were investigated for their ability to develop direct-tolerance or cross-tolerance to sodium chloride, potassium chloride, lactic acid, acetic acid, and ciprofloxacin after habituation in subinhibitory amounts ( of the minimum inhibitory concentration – (MIC) and of the minimum inhibitory concentration – MIC) of Origanum vulgare L. essential oil (OVEO) at different time intervals. The habituation of S. enterica to OVEO did not induce direct-tolerance or cross-tolerance in the tested strains, as assessed by the modulation of MIC values. However, cells habituated to OVEO maintained or increased susceptibility to the tested antimicrobials agents, with up to fourfold double dilution decrease from previously determined MIC values. This study reports for the first time the non-inductive effect of OVEO on the acquisition of direct-tolerance or cross-tolerance in multidrug-resistant S. enterica strains to antimicrobial agents that are largely used in food preservation, as well as to CIP, the therapeutic drug of salmonellosis. PMID:25566231

Comparative In Vitro Activities of ABT-773 against 362 Clinical Isolates of Anaerobic Bacteria

PubMed Central

Citron, Diane M.; Appleman, Maria D.

2001-01-01

The activity of ABT-773, a novel ketolide antibiotic, against clinical isolates of anaerobic bacteria was determined and compared to the activities of other antimicrobial agents. MICs at which 90% of isolates were inhibited (MIC90s) were ≤0.06 μg/ml for Actinomyces spp., Clostridium perfringens, Peptostreptococcus spp., Propionibacterium spp., and Porphyromonas spp. The MIC50s and MIC90s were ≤0.06 and >32 μg/ml, respectively, for Eubacterium spp., Lactobacillus spp., Clostridium difficile, and Clostridium ramosum. The MIC90 for Bilophila wadsworthia, Bacteroides ureolyticus, and Campylobacter gracilis was 1 μg/ml, and that for Prevotella bivia and other Prevotella spp. was 0.5 μg/ml. The MIC90 for Fusobacterium nucleatum was 8 μg/ml, and that for Fusobacterium mortiferum and Fusobacterium varium was >32 μg/ml. The MIC90s for the Bacteroides fragilis group were as follows: for B. fragilis, 8 μg/ml; for Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides distasonis, and Bacteroides uniformis, >32 μg/ml; and for Bacteroides vulgatus, 4 μg/ml. Telithromycin MICs for the B. fragilis group were usually 1 to 2 dilutions higher than ABT-773 MICs. For all strains, ABT-773 was more active than erythromycin by 4 or more dilutions, and for some strains this drug was more active than clindamycin. PMID:11120995

Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves.

PubMed

Brentnall, C; Cheng, Z; McKellar, Q A; Lees, P

2012-09-15

The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time-kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation-adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo-determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (C(av)/MIC and C(min)/MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar C(av)/MIC and C(min)/MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK-PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.

In vitro and in vivo activities of posaconazole and amphotericin B in a murine invasive infection by Mucor circinelloides: poor efficacy of posaconazole.

PubMed

Salas, Valentina; Pastor, F Javier; Calvo, Enrique; Alvarez, Eduardo; Sutton, Deanna A; Mayayo, Emilio; Fothergill, Anette W; Rinaldi, Michael G; Guarro, Josep

2012-05-01

The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥ 3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivo studies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivo efficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloides or by strains of Mucor not identified to the species level.

Investigation of the antimicrobial activities of Snakin-Z, a new cationic peptide derived from Zizyphus jujuba fruits.

PubMed

Daneshmand, Fatemeh; Zare-Zardini, Hadi; Ebrahimi, Leila

2013-01-01

Snakin-Z is a novel antimicrobial peptide (AMP) that is identified from the fruit of Zizyphus jujuba. This peptide is composed of 31 amino acids which is determined with the sequence of CARLNCVPKGTSGNTETCPCYASLHSCRKYG and molecular weight of 3318.82 Da. Snakin-Z is not identical to any AMP in the peptide database. According to this study, Snakin-Z potentially has antimicrobial property against bacteria and fungi. Minimal inhibitory concentration (MIC) value of this peptide is suitable for antimicrobial activity. We assessed that Snakin-Z could affect Phomopsis azadirachtae with the MIC value of 7.65 μg/mL and vice versa Staphylococcus aureus with the MIC value of 28.8 μg/mL. Interestingly, human red blood cells also showed good tolerance to the Snakin-Z. On the basis of this study, Snakin-Z can be an appropriate candidate for therapeutic applications in the future due to its antimicrobial property.

Determination of antibacterial activity of green coffee bean extract on periodontogenic bacteria like Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans: An in vitro study

PubMed Central

Bharath, Nagaraj; Sowmya, Nagur Karibasappa; Mehta, Dhoom Singh

2015-01-01

Background: The aim of this study was to evaluate the antibacterial activity of pure green coffee bean extract on periodonto pathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa). Materials and Methods: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were used to assess the antibacterial effect of pure green coffee bean extract against periodonto pathogenic bacteria by micro dilution method and culture method, respectively. Results: MIC values of Pg, Pi and Aa were 0.2 μg/ml whereas Fn showed sensitive at concentration of 3.125 μg/ml. MBC values mirrors the values same as that of MIC. Conclusion: Antimicrobial activity of pure green coffee bean extract against Pg, Pi, Fn and Aa suggests that it could be recommended as an adjunct to mechanical therapy in the management of periodontal disease. PMID:26097349

In Vitro Structural and Functional Evaluation of Gold Nanoparticles Conjugated Antibiotics

NASA Astrophysics Data System (ADS)

Saha, Biswarup; Bhattacharya, Jaydeep; Mukherjee, Ananda; Ghosh, Anup Kumar; Santra, Chitta Ranjan; Dasgupta, Anjan K.; Karmakar, Parimal

2007-12-01

Bactericidal efficacy of gold nanoparticles conjugated with ampicillin, streptomycin and kanamycin were evaluated. Gold nanoparticles (Gnps) were conjugated with the antibiotics during the synthesis of nanoparticles utilizing the combined reducing property of antibiotics and sodium borohydride. The conjugation of nanoparticles was confirmed by dynamic light scattering (DLS) and electron microscopic (EM) studies. Such Gnps conjugated antibiotics showed greater bactericidal activity in standard agar well diffusion assay. The minimal inhibitory concentration (MIC) values of all the three antibiotics along with their Gnps conjugated forms were determined in three bacterial strains, Escherichia coli DH5α, Micrococcus luteus and Staphylococcus aureus. Among them, streptomycin and kanamycin showed significant reduction in MIC values in their Gnps conjugated form whereas; Gnps conjugated ampicillin showed slight decrement in the MIC value compared to its free form. On the other hand, all of them showed more heat stability in their Gnps conjugated forms. Thus, our findings indicated that Gnps conjugated antibiotics are more efficient and might have significant therapeutic implications.

[Antibiotic resistance analysis of Streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children's Hospital from 2012 to 2014].

PubMed

Ge, L L; Han, Z Y; Liu, A H; Zhu, L; Meng, J H

2017-02-02

Objective: To investigate the antibiotic resistance status of Streptococcus pneumoniae isolates from hospitalized children in Shanxi Children's Hospital. Method: E-test and Kirby-Bauer methods were applied to determine drug sensitivity of the isolates collected from the body fluid specimens of hospitalized children in Shanxi Children's Hospital from January 2012 to December 2014. The antimicrobial sensitivity and minimum inhibitory concentration (MIC) of Streptococcus pneumoniae to the conventional antibiotics were analyzed, in order to compare the annual trends of non-invasive isolates, while the differentiation of sensitivity from specimens. The comparison of rates was performed by Chi-squared test and Fisher's exact test. Result: A total of 671 isolates of streptococcus pneumoniae were obtained, which could be divided as non-invasive isolates(607), invasive isolates from non-cerebrospinal fluid(non-CSF)(40) and invasive isolates from cerebrospinal fluid(CSF)(24). The antimicrobial sensitivity(isolates(%)) of the 671 isolates were respectively vancomycin 671(100.0%), linezolid 671(100.0%), levofloxacin 665(99.1%), penicillin 595(88.7%), ceftriaxone 516(76.9%), cefotaxime 512(76.3%), sulfamethoxazole-trimethoprin(SMZ-TMP) 103(15.4%), clindamycin 28(4.2%), tetracycline 26(3.9%), erythromycin 12(1.8%). From 2012 to 2014, the susceptibility rates of non-invasive isolates to penicillin every year were 95.0%(96/101), 97.3%(110/113), 87.3%(343/393), respectively, and there was significant difference among the three years(χ(2)=13.266, P <0.05), and the values of MIC(50, )MIC(90) and the maximum values of MIC(mg/L) of penicillin were 0.064, 2.000, 6.000 in 2012, which grew up to 1.000, 3.000, 16.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to ceftriaxone and cefotaxime during these three years, (χ(2)=1.172, 1.198, both P >0.05). On the other hand, the values of MIC(50, )MIC(90) and the maximum value of MIC(mg/L) of ceftriaxone and cefotaxime both increased from 0.500, 2.000, 8.000 in 2012 to 0.750, 4.000, 32.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to the rest antibiotic. Based on the same examining standard of CSF, the antimicrobial sensitivity(isolates(%)) of the non-invasive isolates to ceftriaxone, cefotaxime, SMZ-TMP were respectively 281(46.3%), 278(45.8%), 78(12.9%), were significantly lower than the susceptibility rate of the invasive isolates from non-CSF (28(70%), 28(70%), 14(35%), χ(2)=8.453, 8.817, 15.094, all P <0.012 5), and lower than the invasive isolates from CSF (18(75%), 18(75%), χ(2)=7.631, 7.905, P <0.012 5; 11(45.8%), P =0.001). The sensitivity of the isolates to the rest antibiotics were similar( P >0.05). Conclusion: More than 95.0% strains of the streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children's Hospital were sensitive to vancomycin, linezolid, levofloxacin, and the susceptibility rate of penicillin, ceftriaxone, cefotaxime were 88.7%, 76.9%, 76.3%. However, less than 20.0% of streptococcus pneumoniae were sensitive to erythromycin, clindamycin, SMZ-TMP and tetracycline. The susceptibility rate of penicillin of non-invasive Streptococcus pneumoniae declined by these years, and the differences to ceftriaxone and cefotaxime can be neglected, but the values of MIC(50, )MIC(90) and the maximum value of MIC of all were linearly rising. The susceptibility rate of antibiotics to ceftriaxone and cefotaxime of the non-invasive isolates was lower than the invasive isolates.

Multiple Food-Animal-Borne Route in Transmission of Antibiotic-Resistant Salmonella Newport to Humans

PubMed Central

Pan, Hang; Paudyal, Narayan; Li, Xiaoliang; Fang, Weihuan; Yue, Min

2018-01-01

Characterization of transmission routes of Salmonella among various food-animal reservoirs and their antibiogram is crucial for appropriate intervention and medical treatment. Here, we analyzed 3728 Salmonella enterica serovar Newport (S. Newport) isolates collected from various food-animals, retail meats and humans in the United States between 1996 and 2015, based on their minimum inhibitory concentration (MIC) toward 27 antibiotics. Random Forest and Hierarchical Clustering statistic was used to group the isolates according to their MICs. Classification and Regression Tree (CART) analysis was used to identify the appropriate antibiotic and its cut-off value between human- and animal-population. Two distinct populations were revealed based on the MICs of individual strain by both methods, with the animal population having significantly higher MICs which correlates to antibiotic-resistance (AR) phenotype. Only ∼9.7% (267/2763) human isolates could be attributed to food–animal origins. Furthermore, the isolates of animal origin had less diverse antibiogram than human isolates (P < 0.001), suggesting multiple sources involved in human infections. CART identified trimethoprim-sulfamethoxazole to be the best classifier for differentiating the animal and human isolates. Additionally, two typical AR patterns, MDR-Amp and Tet-SDR dominant in bovine- or turkey-population, were identified, indicating that distinct food-animal sources could be involved in human infections. The AR analysis suggested fluoroquinolones (i.e., ciprofloxacin), but not extended-spectrum cephalosporins (i.e., ceftriaxone, cefoxitin), is the adaptive choice for empirical therapy. Antibiotic-resistant S. Newport from humans has multiple origins, with distinct food-animal-borne route contributing to a significant proportion of heterogeneous isolates. PMID:29410657

Antibacterial and antifungal efficacy of fatty acid methyl esters from the leaves of Sesuvium portulacastrum L.

PubMed

Chandrasekaran, M; Senthilkumar, A; Venkatesalu, V

2011-07-01

The fatty acid methyl esters (FAME extract) from Sesuvium (S.) portulacastrum was studied for its fatty acid composition and antimicrobial activity against human pathogenic microorganisms. The gas chromatographic analysis of FAME extract revealed the presence of palmitic acid with the highest relative percentage (31.18%), followed by oleic acid (21.15%), linolenic acid (14.18%) linoleic acid (10.63%), myristic acid (6.91%) and behenic acid (2.42%). The saturated fatty acids were higher than the unsaturated fatty acids. FAME extract showed the highest antibacterial and anticandidal activities and moderate antifungal activity against the tested microorganisms. The highest mean zone of inhibition (16.3 mm) and the lowest MIC (0.25 mg/ml) and MBC (0.5 mg/ml) values were recorded against Bacillus subtilis. The lowest mean zone of inhibition (8.8 mm) and the highest MIC (8 mg/ml) and MFC (16 mg/ml) values were recorded against Aspergillus fumigatus and Aspergillus niger. The results of the present study justify the use of S. portulacastrum in traditional medicine and the FAME extract can be used as a potential antimicrobial agent against the tested human pathogenic microorganisms.

Pharmacokinetics of furagin, a new nitrofurantoin congener, on human volunteers.

PubMed

Männistö, P; Karttunen, P

1979-06-01

The human pharmacokinetics of a nitrofurantoin congener furagin was studied after a single oral dose of 200 mg and during a 9-day continuous treatment with a dose of 100 mg t.i.d. The same dose of nitrofurantoin served as a reference medication. In the acute cross-over phase food greatly speeded up and atropine somewhat retarded the absorption of furagin, but the total absorption remained virtually unchanged as judged from the unchanged AUC values. The furagin concentrations in serum remain several hours above the MIC concentrations of many pathogenic bacteria. Despite the high concentrations in serum, the urine levels of furagin were generally lower than those of nitrofurantoin. The 24 hr recoveries in urine were 8--13% for furagin and about 36% for nitrofurantoin. In the prolonged trial furagin was absorbed and excreted in the same way as in the acute trial. On the 9th day the concentrations in serum and urine were higher than on the first day. The urinary concentrations of both furagin and nitrofurantoin always remained well above the MIC values of the most susceptible bacteria. Several volunteers complained of nightly cramps in their calves after taking furagin for some days, otherwise the side effects were minimal.

Chemical composition, antioxidant and antimicrobial activities of essential oil from Wedelia prostrata

PubMed Central

Dai, Jiali; Zhu, Liang; Yang, Li; Qiu, Jun

2013-01-01

The following study deals with the chemical composition, antioxidant and antimicrobial activity of essential oils of Wedelia prostrata and their main constituents in vitro. A total of 70 components representing 99.26 % of the total oil were identified. The main compounds in the oil were limonene (11.38 %) and α-pinene (10.74 %). Antioxidant assays (1,1-diphenyl-2-picrylhydrazyl, superoxide anion radical, and reducing power test) demonstrate moderate activities for the essential oil and its main components (limonene and α-pinene). The essential oil (1000 μg/disc) exhibited promising antimicrobial activity against 10 strains of test microorganisms as a diameter of zones of inhibition (20.8 to 22.2 mm) and MIC values (125 to 250 µg/ml). The activities of limonene and α-pinene were also determined as main components of the oil. α-Pinene showed higher antimicrobial activity than the essential oil with a diameter of zones of inhibition (20.7 to 22.3 mm) and MIC values (62.5 to 125 µg/ml). The antioxidant and antimicrobial properties of the essential oil may be attributed to the synergistic effects of its diverse major and minor components. PMID:26648809

Antimicrobial activity of juniper berry essential oil (Juniperus communis L., Cupressaceae).

PubMed

Pepeljnjak, Stjepan; Kosalec, Ivan; Kalodera, Zdenka; Blazević, Nikola

2005-12-01

Juniper essential oil (Juniperi aetheroleum) was obtained from the juniper berry, and the GC/MS analysis showed that the main compounds in the oil were alpha-pinene (29.17%) and beta-pinene (17.84%), sabinene (13.55%), limonene (5.52%), and mircene (0.33%). Juniper essential oil was evaluated for the antimicrobial activity against sixteen bacterial species, seven yeast-like fungi, three yeast and four dermatophyte strains. Juniper essential oil showed similar bactericidal activities against Gram-positive and Gram-negative bacterial species, with MIC values between 8 and 70% (V/V), as well as a strong fungicidal activity against yeasts, yeast-like fungi and dermatophytes, with MIC values below 10% (V/V). The strongest fungicidal activity was recorded against Candida spp. (MIC from 0.78 to 2%, V/V) and dermatophytes (from 0.39 to 2%, V/V).

The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives.

PubMed

Wang, Jing; Yang, Teng; Chen, Huang; Xu, Yun-Nan; Yu, Li-Fang; Liu, Ting; Tang, Jie; Yi, Zhengfang; Yang, Cai-Guang; Xue, Wei; Yang, Fan

2017-02-15

A series of novel 9, 13-disubstituted berberine derivatives have been synthesized and evaluated for the antibacterial activities against Staphylococcus aureus, including Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). Compound 20 shows the most potent activity against the growth of Newman strain, with a MIC value of 0.78 μg/mL, which is comparable with the positive control vancomycin. In addition, compound 20, 21, and 33 are highly antistaphylococcal active against five strains of multidrug-resistant S. aureus, with MIC values of 0.78-1.56 μg/mL. Of note, theses antibacterial active compounds have no obvious toxicity to the viability of human fibroblast (HAF) cells at the MIC concentration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

PubMed Central

Pitart, C.; Marco, F.; Keating, T. A.; Nichols, W. W.

2015-01-01

Ceftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200 Enterobacteriaceae and 25 Pseudomonas aeruginosa strains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistant Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBL Escherichia coli (MIC90 of 0.25 mg/liter), ESBL Klebsiella pneumoniae (MIC90 of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90 of 1 mg/liter), non-ESBL E. coli (MIC90 of ≤0.125 mg/liter), non-ESBL K. pneumoniae (MIC90 of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90 of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant P. aeruginosa strains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90 of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtained in vitro from two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90 values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains of Enterobacteriaceae and P. aeruginosa were ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affect Enterobacteriaceae and P. aeruginosa susceptibility to ceftazidime-avibactam; that is, there is no cross-resistance. PMID:25753646

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia

PubMed Central

Lee, Hao-Yuan; Chen, Chyi-Liang; Liu, Shu-Ying; Yan, Yu-Shan; Chang, Chee-Jen; Chiu, Cheng-Hsun

2015-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial. Methods A retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed. Results Most MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759). Conclusions Giving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality. PMID:26295150

Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.

PubMed

Pajot, O; Burdet, C; Couffignal, C; Massias, L; Armand-Lefevre, L; Foucrier, A; Da Silva, D; Lasocki, S; Laouénan, C; Mentec, H; Mentré, F; Wolff, M

2015-05-01

Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

In vitro susceptibility testing of Aspergillus spp. against voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin.

PubMed

Shi, Jun-yan; Xu, Ying-chun; Shi, Yi; Lü, Huo-xiang; Liu, Yong; Zhao, Wang-sheng; Chen, Dong-mei; Xi, Li-yan; Zhou, Xin; Wang, He; Guo, Li-na

2010-10-01

During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting. The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35°C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software. The MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 µg/ml whereas the MIC(90) against A. niger was 0.19 µg/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 µg/ml in all 7 strains tested. The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

Combined Activity of Colloid Nanosilver and Zataria Multiflora Boiss Essential Oil-Mechanism of Action and Biofilm Removal Activity.

PubMed

Shirdel, Maryam; Tajik, Hossein; Moradi, Mehran

2017-12-01

Purpose: The aim of this study was to investigate antimicrobial and biofilm removal potential of Zataria multiflora essential oil (ZEO) and silver nanoparticle (SNP) alone and in combination on Staphylococcus aureus and Salmonella Typhimurium and evaluate the mechanism of action. Methods: The minimum inhibitory concentration (MIC), and optimal inhibitory combination (OIC) of ZEO and SNP were determined according to fractional inhibitory concentration (FIC) method. Biofilm removal potential and leakage pattern of 260-nm absorbing material from the bacterial cell during exposure to the compounds were also investigated. Results: MICs of SNP for both bacteria were the same as 25 μg/ mL. The MICs and MBCs values of ZEO were 2500 and 1250 μg/mL, respectively. The most effective OIC value for SNP and ZEO against Salm. Typhimurium and Staph. aureus were 12.5, 625 and 0.78, 1250 μg/ mL, respectively. ZEO and SNP at MIC and OIC concentrations represented a strong removal ability (>70%) on biofilm. Moreover, ZEO at MIC and OIC concentrations did a 6-log reduction of primary inoculated bacteria during 15 min contact time. The effect of ZEO on the loss of 260-nm material from the cell was faster than SNP during 15 and 60 min. Conclusion: Combination of ZEO and SNP had significant sanitizing activity on examined bacteria which may be suitable for disinfecting the surfaces.

In vitro activity of five tetracyclines and some other antimicrobial agents against four porcine respiratory tract pathogens.

PubMed

Pijpers, A; Van Klingeren, B; Schoevers, E J; Verheijden, J H; Van Miert, A S

1989-09-01

The minimal inhibitory concentrations (MIC) of five tetracyclines and ten other antimicrobial agents were determined for four porcine bacterial respiratory tract pathogens by the agar dilution method. For the following oxytetracycline-susceptible strains, the MIC50 ranges of the tetracyclines were: P. multocida (n = 17) 0.25-0.5 micrograms/ml; B. bronchiseptica (n = 20) 0.25-1.0 micrograms/ml; H. pleuropneumoniae (n = 20) 0.25-0.5 micrograms/ml; S. suis Type 2 (n = 20) 0.06-0.25 micrograms/ml. For 19 oxytetracycline-resistant P. multocida strains the MIC50 of the tetracyclines varied from 64 micrograms/ml for oxytetracycline to 0.5 micrograms/ml for minocycline. Strikingly, minocycline showed no cross-resistance with oxytetracycline, tetracycline, chlortetracycline and doxycycline in P. multocida and in H. pleuropneumoniae. Moreover, in susceptible strains minocycline showed the highest in vitro activity followed by doxycycline. Low MIC50 values were observed for chloramphenicol, ampicillin, flumequine, ofloxacin and ciprofloxacin against P. multocida and H. pleuropneumoniae. B. bronchiseptica was moderately susceptible or resistant to these compounds. As expected tiamulin, lincomycin, tylosin and spiramycin were not active against H. pleuropneumoniae. Except for flumequine, the MIC50 values of nine antimicrobial agents were low for S. suis Type 2. Six strains of this species showed resistance to the macrolides and lincomycin.

Chemical Composition and Antibacterial Activity of the Essential Oil of Vitex agnus-castus L. (Lamiaceae).

PubMed

Gonçalves, Regiane; Ayres, Vanessa F S; Carvalho, Carlos E; Souza, Maria G M; Guimarães, Anderson C; Corrêa, Geone M; Martins, Carlos H G; Takeara, Renata; Silva, Eliane O; Crotti, Antônio E M

2017-01-01

Abnormal multiplication of oral bacteria causes dental caries and dental plaque. These diseases continue to be major public health concerns worldwide, mainly in developing countries. In this study, the chemical composition and antimicrobial activity of the essential oil of Vitex agnus-castus leaves (VAC‒EO) collected in the North of Brazil against a representative panel of cariogenic bacteria were investigated. The antimicrobial activity of VAC-EO was evaluated in terms of its minimum inhibitory concentration (MIC) values by using the broth microdilution method in 96-well microplates. The chemical constituents of VAC-EO were identified by gas chromatography (GC‒FID) and gas chromatography‒mass spectrometry (GC‒MS). VAC‒EO displayed some activity against all the investigated oral pathogens; MIC values ranged from 15.6 to 200 μg/mL. VAC-EO had promising activity against Streptococcus mutans (MIC= 15.6 μg/mL), Lactobacillus casei (MIC= 15.6 μg/mL), and Streptococcus mitis (MIC= 31.2 μg/mL). The compounds 1,8-cineole (23.8%), (E)-β-farnesene (14.6%), (E)-caryophyllene (12.5%), sabinene (11.4%), and α-terpinyl acetate (7.7%) were the major chemical constituents of VAC‒EO. VAC-EO displays antimicrobial activity against cariogenic bacteria. The efficacy of VAC-EO against S. mutans is noteworthy and should be further investigated.

Achievement of trifecta in minimally invasive partial nephrectomy correlates with functional preservation of operated kidney: a multi-institutional assessment using MAG3 renal scan.

PubMed

Zargar, Homayoun; Porpiglia, Francesco; Porter, James; Quarto, Giuseppe; Perdona, Sisto; Bertolo, Riccardo; Autorino, Riccardo; Kaouk, Jihad H

2016-07-01

To validate and compare the values of "MIC" and "trifecta" as predictors of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive PN. We retrospectively reviewed records of consecutive cases of minimally invasive PN performed for cT1 renal masses in 4 centers from 2009 to 2013. Inclusion criteria consisted of availability of a renal scan obtained within 2 weeks prior to surgery and follow-up renal scan 3-6 months after the surgery. The primary endpoint of the study was to compare the degree of ipsilateral renal function preservation assessed by MAG3 renal scan in relation to achievement of MIC and trifecta. Total of 351 patients met our inclusion criteria. The rates of trifecta achievement for cT1a and cT1b tumors were 78.9 and 60.6 %, respectively. The rate of MIC achievement for cT1a tumors and cT1b tumors was 60.3 and 31.7 %, respectively. On multivariable linear regression model, only the degree of tumor complexity assessed by R.E.N.A.L nephrometry score [coefficient B -1.8 (-2.7, -0.9); p < 0.0001] and the achievement of trifecta [coefficient B 6.1 (2.4,9.8); p = 0.014] or MIC (coefficient B 7.2 (3.8,0.6); p < 0.0001) were significant clinical factors predicting ipsilateral split function preservation. Achievement of both MIC and "trifecta" is associated with higher proportion of split renal function preservation for cT1 tumors after minimally invasive PN. Thus, these outcome measures can be regarded not only as markers of surgical quality, but also as reliable surrogates for predicting functional outcome in the operated kidney.

Effect of nanoliposomes containing Zataria multiflora Boiss. essential oil on gene expression of Shiga toxin 2 in Escherichia coli O157:H7.

PubMed

Khatibi, S A; Misaghi, A; Moosavy, M H; Akhondzadeh Basti, A; Mohamadian, S; Khanjari, A

2018-02-01

Enterohaemorrhagic Escherichia coli serotype O157:H7 as a major human pathogen is responsible for food borne outbreaks, bloody diarrhoea, haemorrhagic colitis and haemolytic uraemic syndrome and even death. In this study, the antibacterial activity of the Zataria multiflora essential oil (ZMEO) and nanoliposome-encapsulated ZMEO was evaluated on the pathogenicity of E. coli O157:H7. The minimum inhibitory concentrations (MIC) of essential oil (EO) were determined against the bacterium before and after encapsulation into nanoliposome. Then, the effect of subinhibitory concentrations was evaluated on Shiga toxin 2 (Stx2) production. The effect of free and nanoliposomal EO was also studied on the gene expression of Stx2 by real-time PCR. It was found that inhibitory activity of EO was improved after incorporation into nanoliposomes (P < 0·05). The MIC of free EO against E. coli O157:H7 was 0·03% (v/v), while this value decreased to 0·015%, after encapsulation of EO into nanoliposomes. Furthermore, subinhibitory concentrations of liposomal EO (50 and 75% MIC) had significantly higher inhibitory effect on Stx2 titre than its free form (P < 0·05). Sub-MICs of nanoencapsulated EO also showed a better activity in reduction of Stx2A gene expression than free EO. Using 75% MIC of nanoliposomal EO, the relative transcriptional level of Stx2A gene was decreased from 0·721 to 0·646. The findings of present study suggest that application of nanoliposomes can improve the antibacterial effect of EOs like ZMEO. Due to the enhancement of antimicrobial activity, nanoencapsulation of plant EOs and extracts may increase their commercial application not only in food area but also in the pharmaceutics, cosmetics and health products. © 2017 The Society for Applied Microbiology.

The Effect of Polyherbal Medicines Used for the Treatment of Tuberculosis on Other Opportunistic Organisms of Humans Infected with Tuberculosis.

PubMed

Famewo, Elizabeth Bosede; Clarke, Anna Maria; Afolayan, Anthony Jide

2017-10-01

In many immunocompromised patients, opportunistic bacterial and fungal infections are common. Polyherbal medicines examined in this study are used by the indigenous people of South Africa for the treatment of tuberculosis (TB) and other opportunistic infections associated with TB. To evaluate the antibacterial and antifungal activity of nine polyherbal remedies against four Gram-positive and Gram-negative bacteria respectively and three fungi. Agar dilution method was used to determine the minimum inhibitory concentration (MIC) of the remedies against the organisms. The inhibitory activity of the polyherbal medicines based on the overall MIC revealed that HBfs and FB remedies were the most active remedies against the bacterial isolates at the concentration of 2.5 mg/mL, followed by HBts remedy at 5.0 mg/mL. However, the MIC valves of KWTa, KWTb, KWTc, HBss, EL and AL remedies were higher than 5.0 mg/mL which was the highest concentration used. Only KWTa remedy showed activity against Aspergillus niger and Aspergillus fumigatus with the MIC value of 2.5 mg/mL. While KWTc and HBts had the highest activity at 1.25 mg/mL against Candida albicans , the remaining remedies were active at 2.5 mg/mL. This study revealed that some of these polyherbal formulations have activities against some of the opportunistic bacterial and fungal isolates associated with TB patients. The capability of these remedies to inhibit the organisms is an indication that they are a potential broad-spectrum antimicrobial agent. However, the remedies that are inactive might contain stimulant effects on the immune system. In the Eastern Cape Province of South Africa, no study has been reported on the effect of polyherbal remedies used for the treatment of TB on the opportunistic pathogen. This study therefore revealed that some of the polyherbal medicines possess activity against bacterial and fungal pathogens. Abbreviations used: TB: Tuberculosis; MIC: Minimum Inhibitory Concentration; CFU/ML: Colony Forming Unit Per Mill.

Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species.

PubMed

Lackner, Michaela; de Hoog, G Sybren; Verweij, Paul E; Najafzadeh, Mohammad J; Curfs-Breuker, Ilse; Klaassen, Corné H; Meis, Jacques F

2012-05-01

Since the separation of Pseudallescheria boydii and P. apiosperma in 2010, limited data on species-specific susceptibility patterns of these and other species of Pseudallescheria and its anamorph Scedosporium have been reported. This study presents the antifungal susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates (n = 332) from a wide range of sources and origins were identified down to species level and tested according to CLSI M38-A2 against eight antifungal compounds. Whereas P. apiosperma (geometric mean MIC/minimal effective concentration [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and P. boydii (geometric mean MIC/MEC values of 0.7, 1.3, 5.7, 13.8, 0.5, 1.4, 2.3, and 11.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) had similar susceptibility patterns, those for S. aurantiacum, S. prolificans, and S. dehoogii were different from each other. Voriconazole was the only drug with significant activity against S. aurantiacum isolates. The MIC distributions of all drugs except voriconazole did not show a normal distribution and often showed two subpopulations, making a species-based prediction of antifungal susceptibility difficult. Therefore, antifungal susceptibility testing of all clinical isolates remains essential for targeted antifungal therapy. Voriconazole was the only compound with low MIC values (MIC(90) of ≤ 2 μg/ml) for P. apiosperma and P. boydii. Micafungin and posaconazole showed moderate activity against the majority of Scedosporium strains.

Species-Specific Antifungal Susceptibility Patterns of Scedosporium and Pseudallescheria Species

PubMed Central

Lackner, Michaela; de Hoog, G. Sybren; Verweij, Paul E.; Najafzadeh, Mohammad J.; Curfs-Breuker, Ilse; Klaassen, Corné H.

2012-01-01

Since the separation of Pseudallescheria boydii and P. apiosperma in 2010, limited data on species-specific susceptibility patterns of these and other species of Pseudallescheria and its anamorph Scedosporium have been reported. This study presents the antifungal susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates (n = 332) from a wide range of sources and origins were identified down to species level and tested according to CLSI M38-A2 against eight antifungal compounds. Whereas P. apiosperma (geometric mean MIC/minimal effective concentration [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and P. boydii (geometric mean MIC/MEC values of 0.7, 1.3, 5.7, 13.8, 0.5, 1.4, 2.3, and 11.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) had similar susceptibility patterns, those for S. aurantiacum, S. prolificans, and S. dehoogii were different from each other. Voriconazole was the only drug with significant activity against S. aurantiacum isolates. The MIC distributions of all drugs except voriconazole did not show a normal distribution and often showed two subpopulations, making a species-based prediction of antifungal susceptibility difficult. Therefore, antifungal susceptibility testing of all clinical isolates remains essential for targeted antifungal therapy. Voriconazole was the only compound with low MIC values (MIC90 of ≤2 μg/ml) for P. apiosperma and P. boydii. Micafungin and posaconazole showed moderate activity against the majority of Scedosporium strains. PMID:22290955

Antibacterial activities of the methanol extracts, fractions and compounds from Fagara tessmannii.

PubMed

Tankeo, Simplice B; Damen, Francois; Awouafack, Maurice D; Mpetga, James; Tane, Pierre; Eloff, Jacobus N; Kuete, Victor

2015-07-01

Fagara tessmannii is a shrub of the African rainforests used to treat bacterial infections, cancers, swellings and inflammation. In the present study, the methanol extract from the leaves (FTL), bark (FTB), and roots (FTR) of this plant as well as fractions (FTR1-5) and compounds isolated from FTR namely β-sitosterol-3-O-β-d-glucopyranoside (1), nitidine chloride (2) and buesgenine (3), were tested for their antimicrobial activities against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; Column chromatography was used for the fractionation and purification of the roots extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Results of the MIC determinations indicated that the crude extracts from the roots as well as fraction FTRa4 were active on all the 26 tested bacterial strains. MIC values below 100µg/mL were obtained with roots, leaves and bark extract respectively against 30.8%, 15.4% and 11.5% tested bacteria. The lowest MIC value below of 8µg/mL was obtained with extract from the roots against Escherichia coli MC100 strain. The lowest MIC value of 4µg/mL was also obtained with compound 3 against E. coli AG102 and Klebsiella pneumoniae ATCC11296 CONCLUSIONS: The present study demonstrates that F. tessmannii is a potential source of antimicrobial drugs to fight against MDR bacteria. Benzophenanthrine alkaloids 2 and 3 are the main antibacterial consituents of the roots of the plant. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Relationship between Fosfomycin Exposure and Amplification of Escherichia coli Subpopulations with Reduced Susceptibility in a Hollow-Fiber Infection Model.

PubMed

VanScoy, Brian; McCauley, Jennifer; Bhavnani, Sujata M; Ellis-Grosse, Evelyn J; Ambrose, Paul G

2016-09-01

Understanding the relationship between antibiotic exposure and amplification of bacterial subpopulations with reduced drug susceptibility over time is important for evaluating the adequacy of dosing regimens. We utilized a hollow-fiber infection model to identify the fosfomycin intravenous dosing regimens that prevented the amplification of Escherichia coli bacterial subpopulations with reduced fosfomycin susceptibility. The challenge isolate was E. coli ATCC 25922 (agar MIC with glucose-6-phosphate, 1 mg/liter; agar MIC without glucose-6-phosphate, 32 mg/liter). The fosfomycin dosing regimens studied were 1 to 12 g every 8 h for 10 days to approximate that planned for clinical use. The studies included a no-treatment control regimen. Two bacterial subpopulations were identified, one with reduced susceptibility with agar MIC values ranging from 32 to 128 mg/liter and the other resistant with agar MIC values of 256 to >1,024 mg/liter on plates containing 5× and 256× the baseline MIC value, respectively. An inverted-U-shaped function best described the relationship between the amplification of the two bacterial subpopulations and drug exposure. The lowest fosfomycin dosing regimen that did not amplify a bacterial subpopulation with reduced susceptibility was 4 g administered every 8 h. Nearly immediate amplification of bacterial subpopulations with reduced susceptibility was observed with fosfomycin dosing regimens consisting of 1 to 2 g every 8 h. These data will be useful to support the selection of fosfomycin dosing regimens that minimize the potential for on-therapy amplification of bacterial subpopulations with reduced susceptibility. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Antimicrobial Susceptibility of Udder Pathogens Isolated from Dairy Herds in the West Littoral Region of Uruguay

PubMed Central

2002-01-01

A total of 522 strains belonging to streptococci, enterococci and staphylococci isolated from sub-clinical and clinical cases of bovine mastitis from the west littoral region of Uruguay were analysed for their susceptibility to several antimicrobial agents. The susceptibility patterns were studied by agar disk diffusion methods (ADDM) and broth micro-dilution to determine the minimum inhibitory concentration (MIC). The concentration that inhibits 90% (MIC90) of the analysed strains reported in micrograms per millilitre, for Staphylococcus aureus were > 8, 8, ≤ 0.5, ≤ 4, ≤ 1, ≤ 0.5, > 64, ≤ 0.25, 0.5, ≤ 1 and ≤ 1 to penicillin, ampicillin, oxacillin, cephalotin, gentamicin, erythromycin, oxitetracycline, enrofloxacin, trimethoprim/sulfamethoxazole, neomycin, and clindamycin, respectively. Coagulase-negative staphylococci (CNS) had different values for penicillin (4) and ampicillin (2), while the other antimicrobial agents had the same MIC90 values as reported for S. aureus. The MIC90 values for streptococci were 0.12, 0.25, ≤ 4, 16, ≤ 0.25, 0.5, 0.25 for penicillin, ampicillin, cephalotin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, whereas MIC90 for enterococci were 4, 4, 4, ≤ 0.5, 2, > 8 for penicillin, ampicillin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, respectively. Of 336 strains of S. aureus, 160 (47.6%) were resistant to penicillin. For 41 CNS strains, 10 (27%) presented penicillin-resistance. All the streptococcal strains were susceptible to penicillin, while 3 (7%) of the 43 enteroccocal strains were resistant. Non significant statistical differences were found between the results obtained by ADDM and broth micro-dilution for classifying bacterial isolates as susceptible or resistant according to the National Committee of Clinical Laboratory Standards. PMID:12071114

Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa

PubMed Central

Fazly Bazzaz, Bibi Sedigheh; Sarabandi, Sahar; Khameneh, Bahman; Hosseinzadeh, Hossein

2016-01-01

Objectives: Bacterial resistant infections have become a global health challenge and threaten the society’s health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus) and the standard strain of Pseudomonas aeruginosa (P. aeruginosa). Methods: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI). Results: The MICs of gentamicin against bacterial strains were in the range of 0.312 - 320 μg/mL. The MIC values of both types of catechins were 62.5 - 250 μg/ mL. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance. PMID:28097041

Epidemiological cut-off values for Flavobacterium psychrophilum MIC data generated by a standard test protocol.

PubMed

Smith, P; Endris, R; Kronvall, G; Thomas, V; Verner-Jeffreys, D; Wilhelm, C; Dalsgaard, I

2016-02-01

Epidemiological cut-off values were developed for application to antibiotic susceptibility data for Flavobacterium psychrophilum generated by standard CLSI test protocols. The MIC values for ten antibiotic agents against Flavobacterium psychrophilum were determined in two laboratories. For five antibiotics, the data sets were of sufficient quality and quantity to allow the setting of valid epidemiological cut-off values. For these agents, the cut-off values, calculated by the application of the statistically based normalized resistance interpretation method, were ≤16 mg L(-1) for erythromycin, ≤2 mg L(-1) for florfenicol, ≤0.025 mg L(-1) for oxolinic acid (OXO), ≤0.125 mg L(-1) for oxytetracycline and ≤20 (1/19) mg L(-1) for trimethoprim/sulphamethoxazole. For ampicillin and amoxicillin, the majority of putative wild-type observations were 'off scale', and therefore, statistically valid cut-off values could not be calculated. For ormetoprim/sulphadimethoxine, the data were excessively diverse and a valid cut-off could not be determined. For flumequine, the putative wild-type data were extremely skewed, and for enrofloxacin, there was inadequate separation in the MIC values for putative wild-type and non-wild-type strains. It is argued that the adoption of OXO as a class representative for the quinolone group would be a valid method of determining susceptibilities to these agents. © 2014 John Wiley & Sons Ltd.

Microdilution Susceptibility Testing of Amphotericin B, Itraconazole, and Voriconazole against Clinical Isolates of Aspergillus and Fusarium Species

PubMed Central

Arikan, Sevtap; Lozano-Chiu, Mario; Paetznick, Victor; Nangia, Sunaina; Rex, John H.

1999-01-01

We compared the activities of amphotericin B, itraconazole, and voriconazole against clinical Aspergillus (n = 82) and Fusarium (n = 22) isolates by a microdilution method adopted from the National Committee for Clinical Laboratory Standards (NCCLS-M27A). RPMI 1640 (RPMI), RPMI 1640 supplemented to 2% glucose (RPMI-2), and antibiotic medium 3 supplemented to 2% glucose (AM3) were used as test media. MICs were determined after 24, 48, and 72 h. A narrow range of amphotericin B MICs was observed for Aspergillus isolates, with minor variations among species. MICs for Fusarium isolates were higher than those for Aspergillus isolates. MICs of itraconazole were prominently high for two previously defined itraconazole-resistant Aspergillus fumigatus isolates and Fusarium solani. Voriconazole showed good in vitro activity against itraconazole-resistant isolates, but the MICs of voriconazole for F. solani were high. RPMI was the most efficient medium for detection of itraconazole-resistant isolates, followed by RPMI-2. While the significance remains unclear, AM3 lowered the MICs, particularly those of amphotericin B. PMID:10565912

In Vitro Antimicrobial Activity and Downregulation of Virulence Gene Expression on Helicobacter pylori by Reuterin.

PubMed

Urrutia-Baca, Víctor Hugo; Escamilla-García, Erandi; de la Garza-Ramos, Myriam Angélica; Tamez-Guerra, Patricia; Gomez-Flores, Ricardo; Urbina-Ríos, Cynthia Sofía

2018-06-01

Helicobacter pylori is an infectious agent commonly associated with gastrointestinal diseases. The use of probiotics to treat this infection has been documented, however, their potential antimicrobial metabolites have not yet been investigated. In the present study, the effect of reuterin produced by Lactobacillus reuteri on H. pylori growth and virulence gene expression was evaluated. It was observed that reuterin caused significant (P < 0.05) H. pylori growth inhibition at concentrations from 0.08 to 20.48 mM, with minimal inhibitory concentrations (MICs) of 20.48 mM for H. pylori ATCC700824 and 10.24 mM for H. pylori ATCC43504. In a reuterin bacterial killing assay, it was observed that half of the MIC value for H. pylori (ATCC700824) significantly (P < 0.01) reduced colony numbers from 5.65 ± 0.35 to 3.78 ± 0.35 Log 10 CFU/mL after 12 h of treatment and then increased them to 5.25 ± 0.23 Log 10 CFU/mL at 24 h; at its MIC value (20.48 mM), reuterin abrogated (P < 0.01) H. pylori (ATCC700824) growth after 20 h of culture. In addition, reuterin significantly (P < 0.01) reduced H. pylori (ATCC 43504) colony numbers from 5.65 ± 0.35 to 4.1 ± 0.12 Log10 CFU/mL from 12 to 24 h of treatment and abrogated its growth at its MIC value (10.24 mM), after 20 h of treatment. Reuterin did not alter normal human gastric Hs738.St/Int cell viability at the concentrations tested for H. pylori strains. Furthermore, 10 μM reuterin was shown to significantly (P < 0.01) reduce mRNA relative expression levels of H. pylori virulence genes vacA and flaA at 3 h post-treatment, whose effect was higher at 6 h post-treatment, as measured by RT-qPCR. The observed direct antimicrobial effect and the downregulation of expression of virulence genes on H. pylori by reuterin may contribute to the understanding of the mechanisms of action of probiotics against H. pylori.

In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program.

PubMed

Flamm, R K; Rhomberg, P R; Sader, H S

2017-12-01

Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in phase 2 development for treatment of community-acquired bacterial pneumonia (CABP). A total of 4,739 nonduplicate isolates were selected from a 2014 global surveillance program at medical institutions located in 43 countries within the United States, Europe, Latin America, and the Asia-Pacific region. Nafithromycin and comparator agents were used for susceptibility testing by reference broth microdilution methods. Nafithromycin was active against Staphylococcus aureus (MIC 50/90 , 0.06/>2 μg/ml), including erythromycin-resistant strains exhibiting an inducible clindamycin resistance phenotype (MIC 50/90 , 0.06/0.06 μg/ml) and telithromycin-susceptible strains (MIC 50/90 , 0.06/0.06 μg/ml), but it exhibited limited activity against most telithromycin-resistant and clindamycin-resistant isolates that were constitutively resistant to macrolides (MIC 50/90 , >2/>2 μg/ml). Nafithromycin was very active (MIC 50/90 , 0.015/0.06 μg/ml) against 1,911 Streptococcus pneumoniae strains, inhibiting all strains, with MIC values of ≤0.25 μg/ml. Telithromycin susceptibility was 99.9% for Streptococcus pneumoniae strains, and nafithromycin was up to 8-fold more potent than telithromycin. Overall, 37.9% of S. pneumoniae strains were resistant to erythromycin, and 19.7% were resistant to clindamycin. Nafithromycin was highly active against 606 Streptococcus pyogenes strains (MIC 50/90 , 0.015/0.015 μg/ml), inhibiting 100.0% of isolates at ≤0.5 μg/ml, and MIC 50/90 values (0.015/0.015 to 0.03 μg/ml) were similar for the 4 geographic regions. Nafithromycin and telithromycin demonstrated comparable in vitro activities against 1,002 Haemophilus influenzae isolates and 504 Moraxella catarrhalis isolates. Overall, nafithromycin showed potent in vitro activity against a broad range of contemporary (2014) global pathogens. These results support the continued clinical development of nafithromycin for treatment of CABP. Copyright © 2017 American Society for Microbiology.

Head-to-Head Comparison of Inhibitory and Fungicidal Activities of Fluconazole, Itraconazole, Voriconazole, Posaconazole, and Isavuconazole against Clinical Isolates of Trichosporon asahii

PubMed Central

Hazirolan, Gulsen; Canton, Emilia; Sahin, Selma

2013-01-01

Treatment of disseminated Trichosporon infections still remains difficult. Amphotericin B frequently displays inadequate fungicidal activity and echinocandins have no meaningful antifungal effect against this genus. Triazoles are currently the drugs of choice for the treatment of Trichosporon infections. This study evaluates the inhibitory and fungicidal activities of five triazoles against 90 clinical isolates of Trichosporon asahii. MICs (μg/ml) were determined according to Clinical and Laboratory Standards Institute microdilution method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest concentrations that inhibited ∼50 and 100% of growth, respectively). Minimum fungicidal concentrations (MFCs; μg/ml) were determined by seeding 100 μl of all clear MIC wells (using an inoculum of 104 CFU/ml) onto Sabouraud dextrose agar. Time-kill curves were assayed against four clinical T. asahii isolates and the T. asahii ATCC 201110 strain. The MIC-2 (∼50% reduction in turbidity compared to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that inhibited 90% of isolates at 48 h were, respectively, 8/32/64 μg/ml for fluconazole, 1/2/8 μg/ml for itraconazole, 0.12/0.5/2 μg/ml for voriconazole, 0.5/2/4 μg/ml for posaconazole, and 0.25/1/4 μg/ml for isavuconazole. The MIC-0 endpoints yielded more consistent MIC results, which remained mostly unchanged when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and are easier to interpret. Based on the time-kill experiments, none of the drugs reached the fungicidal endpoint (99.9% killing), killing activity being shown but at concentrations not reached in serum. Statistical analysis revealed that killing rates are dose and antifungal dependent. The lowest concentration at which killing activity begins was for voriconazole, and the highest was for fluconazole. These results suggest that azoles display fungistatic activity and lack fungicidal effect against T. asahii. By rank order, the most active triazole is voriconazole, followed by itraconazole ∼ posaconazole ∼ isavuconazole > fluconazole. PMID:23877683

Potential Information Loss Due to Categorization of Minimum Inhibitory Concentration Frequency Distributions.

PubMed

Mazloom, Reza; Jaberi-Douraki, Majid; Comer, Jeffrey R; Volkova, Victoriya

2018-01-01

A bacterial isolate's susceptibility to antimicrobial is expressed as the lowest drug concentration inhibiting its visible growth, termed minimum inhibitory concentration (MIC). The susceptibilities of isolates from a host population at a particular time vary, with isolates with specific MICs present at different frequencies. Currently, for either clinical or monitoring purposes, an isolate is most often categorized as Susceptible, Intermediate, or Resistant to the antimicrobial by comparing its MIC to a breakpoint value. Such data categorizations are known in statistics to cause information loss compared to analyzing the underlying frequency distributions. The U.S. National Antimicrobial Resistance Monitoring System (NARMS) includes foodborne bacteria at the food animal processing and retail product points. The breakpoints used to interpret the MIC values for foodborne bacteria are those relevant to clinical treatments by the antimicrobials in humans in whom the isolates were to cause infection. However, conceptually different objectives arise when inference is sought concerning changes in susceptibility/resistance across isolates of a bacterial species in host populations among different sampling points or times. For the NARMS 1996-2013 data for animal processing and retail, we determined the fraction of comparisons of susceptibility/resistance to 44 antimicrobial drugs of twelve classes of a bacterial species in a given animal host or product population where there was a significant change in the MIC frequency distributions between consecutive years or the two sampling points, while the categorization-based analyses concluded no change. The categorization-based analyses missed significant changes in 54% of the year-to-year comparisons and in 71% of the slaughter-to-retail within-year comparisons. Hence, analyses using the breakpoint-based categorizations of the MIC data may miss significant developments in the resistance distributions between the sampling points or times. Methods considering the MIC frequency distributions in their entirety may be superior for epidemiological analyses of resistance dynamics in populations.

IN VITRO EFFICACY OF EXTRACTS FROM PLANTS USED BY SMALL-HOLDER FARMERS IN THE TREATMENT OF DERMATOPHILOSIS IN CATTLE.

PubMed

Ndhlovu, Daud N; Masika, Patrick J

2017-01-01

Bovine dermatophilosis, an important skin disease of cattle caused by Dermatophilus congolensis , negatively impacts the livelihoods of small-holder farmers in Zimbabwe. This impact is through, morbidity, loss of draught animal power, costs incurred to manage the disease, losses associated with devalued damaged hides and the resultant culling of some of the affected cattle. Due to the inaccessibility of conventional drugs to manage bovine dermatophilosis, farmers have been reported to use local medicinal plants to manage the disease. The aim of the study was to evaluate the in vitro antimicrobial activities of three plants that small-holder farmers in Zimbabwe used to manage bovine dermatophilosis. Dried plant materials were ground into powder and extracted individually using, water, 80 % acetone and 80 % methanol. The antimicrobial properties of the plants were evaluated against two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and one Gram-positive (Staphylococcus aureus) reference bacterial strains. They were further evaluated against a field isolate of Dermatophilus congolensis . The assays used were the disc diffusion, minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Acetone and methanol extracts had superior inhibitory activities than did those of water. Pterocarpus angolensis DC extracts had better inhibitory properties with absolute MIC values of 0.156 - 5 mg/ml, Cissus Quadrangularis L had MIC values in the range 0.156 - 5 mg/ml while that of Catunaregam spinosa Thunb, Terveng was 0.156 - 10 mg/ml. Dermatophilus congolensis was more sensitive to Pterocarpus angolensis DC average MIC = 0.63 mg/ml than to Cissus quadrangularis L average MIC = 1.25 mg/ml and Catunaregam. spinosa Thunb, Terveng average MIC = 2.08 mg/ml. These results suggest the potential antibacterial activities of extracts of the three plants and hence farmers are, in a way, justified in using the plants. Better results (lower MIC) could be obtained by extracting and evaluating pure active compounds of the plants.

Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis

PubMed Central

Andrade, Milene Aparecida; Cardoso, Maria das Graças; Gomes, Marcos de Souza; de Azeredo, Camila Maria Oliveira; Batista, Luís Roberto; Soares, Maurilio José; Rodrigues, Leonardo Milani Avelar; Figueiredo, Ana Cristina S.

2015-01-01

This study had analyzed the antibacterial, antifungal and trypanocidal activity of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons. Activity against the pathogenic bacteria Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , Salmonella choleraesuis and Staphylococcus aureus was evaluated with the agar cavity diffusion method, while activity on the filamentous fungi Aspergillus flavus , Aspergillus niger , Aspergillus carbonarius and Penicillium commune was evaluated by the disk diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both essential oils exhibited low inhibitory effect towards bacteria, showing high MIC values (125–500 μg mL −1 ), with Gram positive bacteria being more susceptible. Better inhibitory effect was obtained for the evaluated fungi, with lower MIC values (7.81–250 μg mL −1 ), being A. flavus the most susceptible species. Both essential oils presented low trypanocidal activity, with IC 50 /24 h values of 209.30 μg mL −1 for S. guianensis and 282.93 μg mL −1 for C. dinisii . Thus, the high values observed for the MIC of evaluated bacteria and for IC 50 /24 h of T. cruzi , suggest that the essential oils have a low inhibitory activity against these microorganisms. In addition, the low MIC values observed for the tested fungi species indicate good inhibitory activity on these microorganisms’s growth. PMID:26221107

Supercritical CO₂ extraction of volatile oils from Sardinian Foeniculum vulgare ssp. vulgare (Apiaceae): chemical composition and biological activity.

PubMed

Piras, Alessandra; Falconieri, Danilo; Porcedda, Silvia; Marongiu, Bruno; Gonçalves, Maria José; Cavaleiro, Carlos; Salgueiro, Ligia

2014-01-01

This article reports the results on the composition and antifungal effect of volatile extracts obtained from the aerial parts of Sardinian wild fennel (Foeniculum vulgare Mill.), by supercritical fluid extraction (SFE) and by hydrodistillation (HD). The extracts were analysed by gas chromatography-mass spectrometry for qualitative composition and gas chromatography-flame ionisation detector to establish the percentage of constituents. The main components were fenchone (7.1% vs. 8.8%), estragole (34.9% vs. 42.6%) and (E)-anethole (24.6% vs. 43.4%) in the SFE and HD extract, respectively. Minimum inhibitory concentrations (MICs) were measured according to the reference Clinical and Laboratory Standards Institute (CLSI) broth macrodilution protocols. Minimum lethal concentrations were determined by subsequent subculturing of the same cell suspensions in solid medium. The essential oil was more active against Candida albicans, whereas the supercritical fluid extract possesses higher activity against Candida guillermondii and Cryptococcus neoformans, with MIC values of 0.32 μL/mL.

In-vitro and in-vivo anti-Trichophyton activity of essential oils by vapour contact.

PubMed

Inouye, S; Uchida, K; Yamaguchi, H

2001-05-01

The minimum inhibitory doses (MIDs) of essential oils by vapour contact to inhibit the growth of Trichophyton mentagrophytes and Trichophyton rubrum on agar medium were determined using airtight boxes. Among seven essential oils examined, cinnamon bark oil showed the least MID, followed by lemongrass, thyme and perilla oils. Lavender and tea tree oils showed moderate MID, and citron oil showed the highest MID, being 320 times higher than that of cinnamon bark oil. The MID values were less than the minimum inhibitory concentration (MIC) values determined by agar dilution assay. Furthermore, the minimum agar concentration (MAC) of essential oils absorbed from vapour was determined at the time of MID determination as the second antifungal measure. The MAC value by vapour contact was 1.4 to 4.7 times less than the MAC remaining in the agar at the time of MIC determination by agar dilution assay. Using selected essential oils, the anti-Trichophyton activity by vapour contact was examined in more detail. Lemongrass, thyme and perilla oils killed the conidia, inhibited germination and hyphal elongation at 1-4 micrograms ml-1 air, whereas lavender oil was effective at 40-160 micrograms ml-1 air. The in-vivo efficacy of thyme and perilla oils by vapour contact was shown against an experimental tinea pedis in guinea pigs infected with T. mentagrophytes. These results indicated potent anti-Trichophyton action of essential oils by vapour contact.

Bioactivity of essential oils extracted from Cupressus macrocarpa branchlets and Corymbia citriodora leaves grown in Egypt.

PubMed

Salem, Mohamed Z M; Elansary, Hosam O; Ali, Hayssam M; El-Settawy, Ahmed A; Elshikh, Mohamed S; Abdel-Salam, Eslam M; Skalicka-Woźniak, Krystyna

2018-01-22

Cupressus macrocarpa Hartw and Corymbia citriodora (Hook.) K.D. Hill & L.A.S. Johnson, widely grown in many subtropical areas, are used for commercial purposes, such as in perfumery, cosmetics, and room fresheners. Their potential as a source of antimicrobial compounds may be useful in different applications. The chemical composition of essential oils (EOs) from C. macrocarpa branchlets and C. citriodora leaves was analyzed by using gas chromatography-mass spectrometry (GC/MS). Antibacterial and antifungal activities were assessed by the micro-dilution method to determine the minimum inhibitory concentrations (MICs), and minimum fungicidal concentrations (MFCs), and minimum bactericidal concentrations (MBCs). Further, the antioxidant capacity of the EOs was determined via 2,2'-diphenypicrylhydrazyl (DPPH) and β-carotene-linoleic acid assays. Terpinen-4-ol (23.7%), α-phellandrene (19.2%), α-citronellol (17.3%), and citronellal were the major constituents of EO from C. macrocarpa branchlets, and α-citronellal (56%), α-citronellol (14.7%), citronellol acetate (12.3%), isopulegol, and eucalyptol were the primary constituents of EO from C. citriodora leaves. Antibacterial activity with MIC values of EO from C. citriodora leaves was ranged from 0.06 mg/mL to 0.20 mg/mL, and MBC from 0.12 mg/mL against E. coli to 0.41 mg/mL. EO from C. macrocarpa branchlets showed less activity against bacterial strains. The MIC values against tested fungi of the EO from C. citriodora ranged from 0.11 to 0.52 mg/mL while for EO from C. macrocarpa from 0.29 to 3.21 mg/mL. The MIC and MFC values of EOs against P. funiculosum were lower than those obtained from Ketoconazole (KTZ) (0.20; 0.45; 0.29 and 0.53 mg/mL, respectively, vs 0.21 and 0.41 mg/mL. Antioxidant activity of the EO from C. citriodora was higher than that of the positive control but lower than that of the standard butylhydroxytoluene (BHT) (IC 50  = 5.1 ± 0.1 μg/mL). The results indicate that the EO from Egyptian trees such as C. citriodora leaves may possesses strong bactericidal and fungicidal activities and can be used as an agrochemical for controlling plant pathogens and in human disease management which will add crop additive value.

Postantibiotic effect and postantibiotic sub-minimum inhibitory concentration effect of valnemulin against Staphylococcus aureus isolates from swine and chickens.

PubMed

Zhao, D H; Yu, Y; Zhou, Y F; Shi, W; Deng, H; Liu, Y H

2014-02-01

The postantibiotic effect (PAE) and postantibiotic sub-minimum inhibitory concentration (MIC) effect (PA-SME) of valnemulin against Staphylococcus aureus were investigated in vitro using a spectrophotometric technique and classic viable count method. A standard curve was constructed by regression analysis of the number of colonies and the corresponding optical density (OD) at 630 nm of the inoculum. After exposure to valnemulin at different concentrations for an hour, the antibiotic was removed by centrifuging and washing. The PA-SMEs were measured after initial exposure to valnemulin at 4 × the MIC, and then, valnemulin was added to reach corresponding desired concentrations in the resuspended culture. Samples were collected hourly until the culture became turbid. The results were calculated by converting the OD values into the counts of bacteria in accordance with the curve. The MIC of valnemulin against eight strains was identically 0.125 μg ml(-1) . The mean PAEs were 2.12 h (1 × MIC) and 5.06 h (4 × MIC), and the mean PA-SMEs were 6.85 h (0.1 × MIC), 9.12 h (0.2 × MIC) and 10.8 h (0.3 × MIC). The results showed that the strains with identical MICs exhibited different PAEs and PA-SMEs. Valnemulin produced prolonged PAE and PA-SME periods for Staph. aureus, supporting a longer dosing interval while formulating a daily administration dosage. In this study, valnemulin demonstrated prolonged postantibiotic effects and postantibiotic sub-MIC effects on strains of Staphylococcus aureus. The strains with identical MICs of valnemulin exhibited different PAEs and PA-SMEs. Staphylococcus aureus isolated from different species has little impact on the postantibiotic effect of valnemulin. The result suggests a longer dosing interval while formulating a daily administration dosage, and it may play a valuable role of valnemulin in treating Staph. aureus infections in animals. © 2013 The Society for Applied Microbiology.

Antifungal efficacy of thymol, carvacrol, eugenol and menthol as alternative agents to control the growth of food-relevant fungi.

PubMed

Abbaszadeh, S; Sharifzadeh, A; Shokri, H; Khosravi, A R; Abbaszadeh, A

2014-06-01

This work is an attempt to examine the antifungal activity of thymol, carvacrol, eugenol and menthol against 11 food-decaying fungi. The susceptibility test for the compounds was carried out in terms of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) using microdilution method in 96 multi-well microtiter plates. Results indicated that all compounds were effective to varying extents against various fungal isolates, with the highest efficacy displayed by carvacrol (mean MIC value: 154.5 μg/mL) (P<0.05). The incorporation of increased concentrations of all compounds to the media led to progressive and significant reduction in growth for all fungi. The most potent inhibitory activity of thymol, carvacrol, eugenol and menthol was found for Cladosporium spp. (MIC: 100 μg/mL), Aspergillus spp. (MIC: 100 μg/mL), Cladosporium spp. (MIC: 350 μg/mL), and Aspergillus spp. and Cladosporium spp. (MIC: 125 μg/mL), respectively. Thus, the application of these herbal components could be considered as a good alternatives to inhibit fungal growth and to reduce the use of synthetic fungicides. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Comparative evaluation of the sensitivity of Acinetobacter to colistin, using the prediffusion and minimum inhibitory concentration methods: detection of heteroresistant isolates].

PubMed

Herrera, Melina E; Mobilia, Liliana N; Posse, Graciela R

2011-01-01

The objective of this study is to perform a comparative evaluation of the prediffusion and minimum inhibitory concentration (MIC) methods for the detection of sensitivity to colistin, and to detect Acinetobacter baumanii-calcoaceticus complex (ABC) heteroresistant isolates to colistin. We studied 75 isolates of ABC recovered from clinically significant samples obtained from various centers. Sensitivity to colistin was determined by prediffusion as well as by MIC. All the isolates were sensitive to colistin, with MIC = 2µg/ml. The results were analyzed by dispersion graph and linear regression analysis, revealing that the prediffusion method did not correlate with the MIC values for isolates sensitive to colistin (r² = 0.2017). Detection of heteroresistance to colistin was determined by plaque efficiency of all the isolates with the same initial MICs of 2, 1, and 0.5 µg/ml, which resulted in 14 of them with a greater than 8-fold increase in the MIC in some cases. When the sensitivity of these resistant colonies was determined by prediffusion, the resulting dispersion graph and linear regression analysis yielded an r² = 0.604, which revealed a correlation between the methodologies used.

Olive leaf extract activity against Candida albicans and C. dubliniensis - the in vitro viability study.

PubMed

Zorić, Nataša; Kopjar, Nevenka; Kraljić, Klara; Oršolić, Nada; Tomić, Siniša; Kosalec, Ivan

2016-09-01

Olive leaf extract is characterized by a high content of polyphenols (oleuropein, hydroxytyrosol and their derivatives), which is associated with its therapeutic properties. The objective of the present research was to evaluate the antifungal activity of olive leaf extract against Candida albicans ATCC 10231 and C. dubliniensis CBS 7987 strains. Minimum inhibitory concentrations (MIC) of the extract were determined by several in vitro assays. The extract showed a concentration depended effect on the viability of C. albicans with MIC value of 46.875 mg mL-1 and C. dubliniensis with MIC value 62.5 mg mL-1. Most sensitive methods for testing the antifungal effect of the extracts were the trypan blue exclusion method and fluorescent dye exclusion method while MIC could not be determined by the method according to the EUCAST recommendation suggesting that herbal preparations contain compounds that may interfere with this susceptibility testing. The fluorescent dye exclusion method was also used for the assessment of morphological changes in the nuclei of treated cells. According to the obtained results, olive leaf extract is less effective against the tested strains than hydroxytyrosol, an olive plant constituent tested in our previous study.

Heparin-benzyl alcohol enhancement of biofilms formation and antifungal susceptibility of vaginal Candida species isolated from pregnant and nonpregnant Saudi women

PubMed Central

Al-akeel, Raid A; El-kersh, Talat A; Al-Sheikh, Yazeed A; Al-Ahmadey, Ziab Zakey

2013-01-01

Biofilm formation by Candida species is a major contribute to their pathogenic potential.The aim of this study was to determine in vitro effects of EDTA, cycloheximide, and heparin-benzyl alcohol preservative on C. albicans (126) and non-albicans (31)vaginal yeast isolates biofilm formations and their susceptibility against three antifungal Etest strips. Results of the crystal violet-assay, indicated that biofilms formation were most commonly observed [100%] for C. kefyr, C. utilis, C. famata, and Rhodotorula mucilaginosa, followed by C. glabrata [70%], C. tropicalis [50%], C. albicans [29%], Saccharomyces cerevisiae [0.0%]. EDTA (0.3mg/ml) significantly inhibited biofilm formation in both C. albicans and non-albicans isolates (P=0.0001) presumably due to chelation of necessary metal cations for the process-completion. In contrast, heparin (-benzyl alcohol preservative) stimulated biofilm formation in all tested isolates, but not at significant level (P=0.567). Conversely, cycloheximide significantly (P=0.0001) inhibited biofilm formation in all C. albicans strains(126) and its effect was even 3 fold more pronounced than EDTA inhibition, probably due to its attenuation of proteins (enzymes) and/or complex molecules necessary for biofilm formation. Results also showed that all nonalbicans yeasts isolates were susceptible to 5-flucytosine (MIC50, 0.016 µg/ml; MIC90, 0.064 µg/ml), but 14% of C. albicans isolates were resistant (MIC50, 0.064 µg/ml; MIC90 >32 µg/ml). The MIC50 value of amphotricin B for all C. albicans and non-albicans isolates was at a narrow range of 0.023 µg /ml, and the MIC90 values were 0.047 µg/ml and 0.064 µg/ml respectively, thereby confirming its efficacy as a first line empiric- treatment of Candida spp infections. PMID:23750080

Chemical composition and antifungal activity of the essential oils of Lavandula viridis L'Her.

PubMed

Zuzarte, Mónica; Gonçalves, Maria José; Cavaleiro, Carlos; Canhoto, Jorge; Vale-Silva, Luís; Silva, Maria João; Pinto, Eugénia; Salgueiro, Lígia

2011-05-01

In the present work we report for what we believe to be the first time the antifungal activity and mechanism of action of the essential oils of Lavandula viridis from Portugal. The essential oils were isolated by hydrodistillation and analysed by GC and GC/MS. The MIC and the minimal lethal concentration (MLC) of the essential oil and its major compounds were determined against several pathogenic fungi. The influence of subinhibitory concentrations of the essential oil on the dimorphic transition in Candida albicans was also studied, as well as propidium iodide and FUN-1 staining of Candida albicans cells by flow cytometry following short treatments with the essential oil. The oils were characterized by a high content of oxygen-containing monoterpenes, with 1,8-cineole being the main constituent. Monoterpene hydrocarbons were present at lower concentrations. According to the determined MIC and MLC values, the dermatophytes and Cryptococcus neoformans were the most sensitive fungi (MIC and MLC values ranging from 0.32 to 0.64 µl ml⁻¹), followed by Candida species (at 0.64-2.5 µl ml⁻¹). For most of these strains, MICs were equivalent to MLCs, indicating a fungicidal effect of the essential oil. The oil was further shown to completely inhibit filamentation in Candida albicans at concentrations well below the respective MICs (as low as MIC/16). Flow cytometry results suggested a mechanism of action ultimately leading to cytoplasmic membrane disruption and cell death. Our results show that L. viridis essential oils may be useful in the clinical treatment of fungal diseases, particularly dermatophytosis and candidosis, although clinical trials are required to evaluate the practical relevance of our in vitro research.

In Vitro Anti-Listerial Activities of Crude n-Hexane and Aqueous Extracts of Garcinia kola (heckel) Seeds

PubMed Central

Penduka, Dambudzo; Okoh, Anthony I.

2011-01-01

We assessed the anti-Listerial activities of crude n-hexane and aqueous extracts of Garcinia kola seeds against a panel of 42 Listeria isolates previously isolated from wastewater effluents in the Eastern Cape Province of South Africa and belonging to Listeria monocytogenes, Listeria grayi and Listeria ivanovii species. The n-hexane fraction was active against 45% of the test bacteria with zones of inhibition ranging between 8–17 mm, while the aqueous fraction was active against 29% with zones of inhibition ranging between 8–11 mm. The minimum inhibitory concentrations (MIC) were within the ranges of 0.079–0.625 mg/mL for the n-hexane extract and 10 to >10 mg/mL for the aqueous extract. The rate of kill experiment carried out for the n-hexane extract only, revealed complete elimination of the initial bacterial population for L. grayi (LAL 15) at 3× and 4× MIC after 90 and 60 min; L. monocytogenes (LAL 8) at 3× and 4× MIC after 60 and 15 min; L. ivanovii (LEL 18) at 3× and 4× MIC after 120 and 15 min; L. ivanovii (LEL 30) at 2, 3 and 4× MIC values after 105, 90 and 15 min exposure time respectively. The rate of kill activities were time- and concentration-dependant and the extract proved to be bactericidal as it achieved a more than 3log10 decrease in viable cell counts after 2 h exposure time for all of the four test organisms at 3× and 4× MIC values. The results therefore show the potential presence of anti-Listerial compounds in Garcinia kola seeds that can be exploited in effective anti-Listerial chemotherapy. PMID:22072929

In vitro anti-listerial activities of crude n-hexane and aqueous extracts of Garcinia kola (heckel) seeds.

PubMed

Penduka, Dambudzo; Okoh, Anthony I

2011-01-01

We assessed the anti-Listerial activities of crude n-hexane and aqueous extracts of Garcinia kola seeds against a panel of 42 Listeria isolates previously isolated from wastewater effluents in the Eastern Cape Province of South Africa and belonging to Listeria monocytogenes, Listeria grayi and Listeria ivanovii species. The n-hexane fraction was active against 45% of the test bacteria with zones of inhibition ranging between 8-17 mm, while the aqueous fraction was active against 29% with zones of inhibition ranging between 8-11 mm. The minimum inhibitory concentrations (MIC) were within the ranges of 0.079-0.625 mg/mL for the n-hexane extract and 10 to >10 mg/mL for the aqueous extract. The rate of kill experiment carried out for the n-hexane extract only, revealed complete elimination of the initial bacterial population for L. grayi (LAL 15) at 3× and 4× MIC after 90 and 60 min; L. monocytogenes (LAL 8) at 3× and 4× MIC after 60 and 15 min; L. ivanovii (LEL 18) at 3× and 4× MIC after 120 and 15 min; L. ivanovii (LEL 30) at 2, 3 and 4× MIC values after 105, 90 and 15 min exposure time respectively. The rate of kill activities were time- and concentration-dependant and the extract proved to be bactericidal as it achieved a more than 3log(10) decrease in viable cell counts after 2 h exposure time for all of the four test organisms at 3× and 4× MIC values. The results therefore show the potential presence of anti-Listerial compounds in Garcinia kola seeds that can be exploited in effective anti-Listerial chemotherapy.

Synergistic effect of artocarpin on antibacterial activity of some antibiotics against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

PubMed

Septama, Abdi Wira; Panichayupakaranant, Pharkphoom

2016-01-01

Antibacterial resistance has dramatically increased and resulted in serious health problems worldwide. One appealing strategy to overcome this resistance problem is the use of combinations of antibacterial compounds to increase their potency. The objective of this study is to determine the synergistic effects of artocarpin for ampicillin, norfloxacin, and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA) as well as the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli. A broth microdilution method (1.95-250 µg/mL) was used to determine the minimum inhibitory concentration (MIC) of artocarpin and the antibiotics. Any synergistic effects were evaluated at their own MIC using the checkerboard method and a time-kill assay at 37 °C for 24 h. Artocarpin showed antibacterial activity against MRSA and E. coli with an MIC value of 62.5 µg/mL, and against P. aeruginosa with an MIC value of 250 µg/mL. The interaction of artocarpin with all tested antibiotics produced synergistic effects against MRSA with a fractional inhibitory concentration index (FICI) of 0.15-0.37. In addition, a combination of artocarpin and norfloxacin showed a synergistic effect against E. coli with an FICI value of 0.37, while the combinations of artocarpin and tetracycline as well as artocarpin and norfloxacin exhibited synergy interactions against P. aeruginosa with FICI values of 0.24 and 0.37, respectively. Time-kill assays indicated that artocarpin enhanced the antimicrobial activities of tetracycline, ampicillin, and norfloxacin against MRSA as well as Gram-negative bacteria.

Antimicrobial, antibiofilm and cytotoxic activities of Hakea sericea Schrader extracts

PubMed Central

Luís, Ângelo; Breitenfeld, Luiza; Ferreira, Susana; Duarte, Ana Paula; Domingues, Fernanda

2014-01-01

Background: Hakea sericea Schrader is an invasive shrub in Portuguese forests. Objective: The goal of this work was to evaluate the antimicrobial activity of H. sericea extracts against several strains of microorganisms, including the ability to inhibit the formation of biofilms. Additionally the cytotoxic properties of these extracts, against human cells, were assessed. Materials and Methods: The antimicrobial activity of the methanolic extracts of H. sericea was assessed by disk diffusion assay and Minimum Inhibitory Concentration (MIC) value determination. The antibiofilm activity was determined by quantification of total biofilm biomass with crystal violet. Cytotoxicity was evaluated by hemolysis assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Results: For Gram-positive bacteria, MIC values of H. sericea methanolic extracts ranged between 0.040 and 0.625 mg/mL, whereas the fruits extract yielded the lowest MIC for several strains of microorganisms, namely, S. aureus, B. cereus, L. monocytogenes and clinical methicillin-resistant S. aureus (MRSA). Stems and fruits extract at 2.5 mg/mL effectively eradicated the biofilm of S. aureus ATCC 25923, SA 01/10 and MRSA 12/10. Regarding leaves extract, hemolysis was not observed, and in the case of stems and fruits, hemolysis was verified only for higher concentrations, suggesting its low toxicity. Fruits extract presented no toxic effect to normal human dermal fibroblasts (NHDF) cells however for concentrations of 0.017 and 0.008 mg/mL this extract was able to decrease human breast adenocarcinoma cells (MCF-7) viability in about 60%, as MTT test results had confirmed. This is a clearly demonstrator of the cytotoxicity of this extract against MCF-7 cells. PMID:24914310

Extracellular Electron Transfer Is a Bottleneck in the Microbiologically Influenced Corrosion of C1018 Carbon Steel by the Biofilm of Sulfate-Reducing Bacterium Desulfovibrio vulgaris.

PubMed

Li, Huabing; Xu, Dake; Li, Yingchao; Feng, Hao; Liu, Zhiyong; Li, Xiaogang; Gu, Tingyue; Yang, Ke

2015-01-01

Carbon steels are widely used in the oil and gas industry from downhole tubing to transport trunk lines. Microbes form biofilms, some of which cause the so-called microbiologically influenced corrosion (MIC) of carbon steels. MIC by sulfate reducing bacteria (SRB) is often a leading cause in MIC failures. Electrogenic SRB sessile cells harvest extracellular electrons from elemental iron oxidation for energy production in their metabolism. A previous study suggested that electron mediators riboflavin and flavin adenine dinucleotide (FAD) both accelerated the MIC of 304 stainless steel by the Desulfovibrio vulgaris biofilm that is a corrosive SRB biofilm. Compared with stainless steels, carbon steels are usually far more prone to SRB attacks because SRB biofilms form much denser biofilms on carbon steel surfaces with a sessile cell density that is two orders of magnitude higher. In this work, C1018 carbon steel coupons were used in tests of MIC by D. vulgaris with and without an electron mediator. Experimental weight loss and pit depth data conclusively confirmed that both riboflavin and FAD were able to accelerate D. vulgaris attack against the carbon steel considerably. It has important implications in MIC failure analysis and MIC mitigation in the oil and gas industry.

Extracellular Electron Transfer Is a Bottleneck in the Microbiologically Influenced Corrosion of C1018 Carbon Steel by the Biofilm of Sulfate-Reducing Bacterium Desulfovibrio vulgaris

PubMed Central

Li, Yingchao; Feng, Hao; Liu, Zhiyong; Li, Xiaogang; Gu, Tingyue; Yang, Ke

2015-01-01

Carbon steels are widely used in the oil and gas industry from downhole tubing to transport trunk lines. Microbes form biofilms, some of which cause the so-called microbiologically influenced corrosion (MIC) of carbon steels. MIC by sulfate reducing bacteria (SRB) is often a leading cause in MIC failures. Electrogenic SRB sessile cells harvest extracellular electrons from elemental iron oxidation for energy production in their metabolism. A previous study suggested that electron mediators riboflavin and flavin adenine dinucleotide (FAD) both accelerated the MIC of 304 stainless steel by the Desulfovibrio vulgaris biofilm that is a corrosive SRB biofilm. Compared with stainless steels, carbon steels are usually far more prone to SRB attacks because SRB biofilms form much denser biofilms on carbon steel surfaces with a sessile cell density that is two orders of magnitude higher. In this work, C1018 carbon steel coupons were used in tests of MIC by D. vulgaris with and without an electron mediator. Experimental weight loss and pit depth data conclusively confirmed that both riboflavin and FAD were able to accelerate D. vulgaris attack against the carbon steel considerably. It has important implications in MIC failure analysis and MIC mitigation in the oil and gas industry. PMID:26308855

Antimicrobial susceptibility of Brachyspira hyodysenteriae in Switzerland.

PubMed

Kirchgässner, C; Schmitt, S; Borgström, A; Wittenbrink, M M

2016-06-01

Brachyspira (B.) hyodysenteriae is the causative agent of swine dysentery (SD), a severe mucohaemorrhagic diarrheal disease in pigs worldwide. So far, the antimicrobial susceptibility patterns of B. hyodysenteriae in Switzerland have not been investigated. Therefore, a panel of 30 porcine B. hyodysenteriae isolates were tested against 6 antimicrobial agents by using the VetMIC Brachy panel, a broth microdilution test. Tiamulin and valnemulin showed high antimicrobial activity inhibiting all isolates at low concentrations. The susceptibility testing of doxycycline revealed values from ≤0.25 μg/ ml (47%) to 2 μg/ml (10%). The MIC values of lincomycin ranged between ≤0.5 μg/ml (30%) and 32 μg/ml (43%). For tylosin, 57% of the isolates could not be inhibited at the highest concentration of ≥128 μg/ml. The MIC values for tylvalosin were between ≤0.25 μg/ml (10%) and 8 μg/ml (20%). These findings reveal Switzerland's favourable situation compared to other European countries. Above all, tiamulin and valnemulin are still effective antimicrobial agents and can be further used for the treatment of SD.

Additive interaction of carbon dots extracted from soluble coffee and biogenic silver nanoparticles against bacteria

NASA Astrophysics Data System (ADS)

Andrade, Patricia F.; Nakazato, Gerson; Durán, Nelson

2017-06-01

It is known the presence of carbon dots (CDs) in carbohydrate based foods. CDs extracted from coffee grounds and instant coffee was also published. CDs from soluble coffee revealed an average size of 4.4 nm. CDs were well-dispersed in water, fluorescent and we have characterized by XPS, XRD analysis, fluorescence and by FTIR spectra. The MIC value by serial micro-dilution assays for CDs on S. aureus ATCC 25923 was 250 μg/mL and E. coli ATCC 25922 >1000 ug/mL. For silver nanoparticles biogenically synthesized was 6.7 μg/mL. Following the checkerboard assay with combining ½ MIC values of the MICs of 125 μg/mL of carbon dots and 3.4 μg/mL of silver nanoparticles, following the fractionated inhibitory concentration (FIC) index methodology, on S. aureus gave a fractionated inhibitory concentration (FIC) value of 1.0, meaning additive interaction. In general, the unfunctionalized CDs showed to be inefficient as antibacterial compounds, however the CDs extracted from Coffee powder and together silver nanoparticles appeared interesting as antibacterial association.

Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin

PubMed Central

Meagher, Alison K.; Forrest, Alan; Dalhoff, Axel; Stass, Heino; Schentag, Jerome J.

2004-01-01

The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma. A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes. A “mixture model” was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment. Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively. The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios. PMID:15155200

Regulation of Serratia marcescens ompF and ompC porin genes in response to osmotic stress, salicylate, temperature and pH.

PubMed

Begic, Sanela; Worobec, Elizabeth A

2006-02-01

Serratia marcescens is a Gram-negative enterobacterium that has become an important opportunistic pathogen, largely due to its high degree of natural antibiotic resistance. One factor contributing to this natural antibiotic resistance is reduced outer membrane permeability, which is controlled in part by OmpC and OmpF porin proteins. OmpF expression is regulated by micF, an RNA transcript encoded upstream of the ompC gene, which hybridizes with the ompF transcript to inhibit its translation. Regulation of S. marcescens porin gene expression, as well as that of micF, was investigated using beta-galactosidase reporter gene fusions in response to 5, 8 and 10 % sucrose, 1, 5 and 8 mM salicylate, and different pH and temperature values. beta-Galactosidase activity assays revealed that a lower growth temperature (28 degrees C), a more basic pH (pH 8), and an absence of sucrose and salicylate induce the transcription of the ompF gene, whereas the induction of ompC is stimulated at a higher growth temperature (42 degrees C), acidic pH (pH 6), and maximum concentrations of sucrose (10 %) and salicylate (8 mM). In addition, when multiple conditions were tested, temperature had the predominant effect, followed by pH. In this study, it was found that the MicF regulatory mechanism does not play a role in the osmoregulation of the ompF and ompC genes, whereas MicF does repress OmpF expression in the presence of salicylate and high growth temperature, and under low pH conditions.

In vitro antimicrobial susceptibility of Mycoplasma bovis isolated in Israel from local and imported cattle.

PubMed

Gerchman, Irena; Levisohn, Sharon; Mikula, Inna; Lysnyansky, Inna

2009-06-12

Monitoring of susceptibility to antibiotics in field isolates of pathogenic bovine mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility profiles of Mycoplasma bovis clinical strains, isolated during 2005-2007 from Israeli and imported calves. Minimal inhibitory concentration (MIC) values were determined for macrolides by the microbroth dilution test, for aminoglycosides by commercial Etest, and for fluoroquinolones and tetracyclines by both methods. Notably, although correlation between the methods was generally good, it was not possible to determine the MIC endpoint for enrofloxacin-resistant strains (MIC > or =2.5 microg/ml in the microtest) by Etest. Comparison of antibiotic susceptibility profiles between local and imported M. bovis strains revealed that local strains were significantly more resistant to macrolides than most isolates from imported animals, with MIC(50) of 128 microg/ml vs. 2 microg/ml for tilmicosin and 8 microg/ml vs. 1 microg/ml for tylosin, respectively. However, local strains were more susceptible than most imported strains to fluoroquinolones and spectinomycin. Difference in susceptibility to tetracycline, doxycycline and oxytetracycline between local and imported strains was expressed in MIC(90) values for imported strains in the susceptible range compared to intermediate susceptibility for local strains. The marked difference in susceptibility profiles of M. bovis strains isolated from different geographical regions seen in this study emphasizes the necessity for performing of the antimicrobial susceptibility testing periodically and on a regional basis.

Efficacy of the Clinical Agent VT-1161 against Fluconazole-Sensitive and -Resistant Candida albicans in a Murine Model of Vaginal Candidiasis

PubMed Central

Hoekstra, W. J.; Schotzinger, R. J.; Sobel, J. D.; Lilly, E. A.; Fidel, P. L.

2015-01-01

Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. PMID:26124165

Susceptibility of Malassezia pachydermatis to aminoglycosides.

PubMed

Silva, Freddy Alejandro; Conde-Felipe, Magnolia; Rosario, Inmaculada; Ferrer, Otilia; Real, Fernando; Déniz, Soraya; Acosta, Félix; Padilla, Daniel; Acosta-Hernández, Begoña

2017-12-01

Previous studies have evaluated the action of gentamicin against Malassezia pachydermatis. The aim of this study was to evaluate in vitro susceptibility of M. pachydermatis to the aminoglycosides- gentamicin, tobramycin, netilmicin and framycetin. The minimum inhibitory concentration (MIC) of gentamicin was determined following methods M27-A3 microdilution and Etest ® . The Etest ® was used to determine the minimum inhibitory concentration (MIC) of the tobramycin and netilmicin. The Kirby-Bauer test was used to determine the antibiotic susceptibility to the framycetin. The MIC50 and MIC90 were 8.12 μg/mL and 32.5 μg/mL by microdilution method for gentamicin. The MIC50, determined by the Etest ® , was 8 μg/mL for gentamicin and netilmicin and 64 μg/mL for tobramycin. The MIC90 was 16 and 32 μg/mL for gentamicin and netilmicin respectively. The MIC90 was outside of the detectable limits for tobramycin. To framycetin, 28 strains (40%) of the 70 M. pachydermatis isolates tested showed a diameter of 22 mm, 22 strains (31.42%) showed a diameter of 20 mm, 16 strains showed a diameter of ≤ 18 mm, and only 5.71% of the isolates showed a diameter of ≥ 22 mm. This study provides evidence of high in vitro activity of the aminoglycosides-gentamicin, tobramycin, netilmicin and framycetin against M. pachydermatis. For gentamicin Etest ® showed similar values of MIC50 y MIC90 that the obtained by microdilution method. We considered Etest ® method could be a good method for these calculations with aminoglycosides. © 2017 Blackwell Verlag GmbH.

Antimicrobial Effects of Garcinia Mangostana on Cariogenic Microorganisms.

PubMed

Janardhanan, Sunitha; Mahendra, Jaideep; Girija, A S Smiline; Mahendra, Little; Priyadharsini, Vijayashree

2017-01-01

Garcinia mangostana commonly called as Mangosteen fruit has been used as an antibacterial agent since age old times. The mangosteen pericarp has proven to have antibacterial effect, but the effect of the same on cariogenic organisms has not been explored. The present study was an attempt to gain a better understanding of the antibacterial effect of mangosteen pericarp on the cariogenic bacteria, to unravel the therapeutic potential for the same. The aim of the study was to assess the antibacterial efficacy of the crude chloroform extract of mangosteen pericarp against cariogenic bacteria. The study was done under laboratory settings using an in vitro design. The microorganisms namely Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius, Streptococcus oralis and Lactobacillus acidophilus were procured from American Type Cell Culture (ATCC) and Microbial Type Culture Collection (MTCC) were revived and lawn cultured. The antibacterial effect of mangosteen pericarp was tested using agar well diffusion method on Trypticase Soy Agar-Blood Agar (TSA-BA) and de Man, Rogosa and Sharpe (MRS) agar media. The standard antiplaque agent chlorhexidine was used as the positive control. This cross-sectional, experimental study was done in Central Research laboratory, Meenakshi Ammal Dental College for period of eight weeks. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values were determined by microbroth dilution method. Statistical analysis was done by calculating the mean of the zones of inhibition on tested microorganisms. Mann-Whitney test was done to compare the zones of inhibition of mangosteen and chlorhexidine. The antibacterial bioassay showed the highest activity for Lactobacillus acidophilus (13.6 mm) and Streptococcus sanguis (13.6 mm), whereas, it showed a medium and low activity for Streptococcus oralis (11.3 mm), Streptococcus mutans (10.6 mm) and Streptococcus salivarius (3 mm) respectively. The MBC and MIC values were lowest for Lactobacillus acidophilus (MIC 25 mg/ml, MBC 50 mg/ml) and Streptococcus oralis (MIC 50 mg/ml, MBC 100 mg/ml). Mangosteen pericarp extract had a higher zone of inhibition against the tested microorganisms which suggests its potent antibacterial action against cariogenic organisms. However, further analytical studies are needed to isolate the key molecules of mangosteen pericarp, to explore its anticariogenic therapeutic potential on gram negative oral microorganisms.

Biocide and antibiotic susceptibility of Salmonella isolates obtained before and after cleaning at six Danish pig slaughterhouses.

PubMed

Gantzhorn, Mette Rørbæk; Pedersen, Karl; Olsen, John Elmerdahl; Thomsen, Line Elnif

2014-07-02

Salmonella sp. continues to be one of the most important foodborne pathogens. Control measures in terms of cleaning and disinfection on food production plants are very important for limiting the risk of contaminated food products to reach the consumer. In the last decade concern has arisen that bacteria exposed to disinfectants can develop resistance toward disinfectants and can have a higher risk of developing antibiotic resistance. The objectives of this study were to examine the prevalence of biocide resistant Salmonella sp. in Danish pig slaughterhouses, to evaluate if there was a correlation between susceptibilities to biocides and antibiotics, and to examine if cleaning and disinfection select isolates with changed susceptibility toward biocides or antibiotics. Salmonella sp. was isolated from the environment in Danish pig slaughterhouses before and after cleaning and disinfection. The susceptibility toward three different biocides, triclosan and two commercial disinfection products: Desinfect Maxi, a quaternary ammonium compound, and Incimaxx DES, an acetic compound, was determined. We found no resistance toward the biocides tested, but we did find that isolates obtained after cleaning had higher minimum inhibitory concentration (MIC) values toward one of the disinfectants (Incimaxx DES) compared to isolates obtained before cleaning and disinfection. This could indicate selection of strains that are more tolerant, due to the cleaning and disinfection. Furthermore, we found that there was a weak statistical correlation between MICs toward the biocides and some antibiotics, but no difference in log(MIC)s toward antibiotics between isolates obtained before and after cleaning, nor did we find any difference in the number of resistances of isolates obtained before and after cleaning and disinfection. Copyright © 2014 Elsevier B.V. All rights reserved.

Simple, direct drug susceptibility testing technique for diagnosis of drug-resistant tuberculosis in resource-poor settings.

PubMed

Kim, C-K; Joo, Y-T; Lee, E P; Park, Y K; Kim, H-J; Kim, S J

2013-09-01

The Korean Institute of Tuberculosis, Seoul, Republic of Korea. To develop a simple, direct drug susceptibility testing (DST) technique using Kudoh-modified Ogawa (KMO) medium. The critical concentrations of isoniazid (INH), rifampicin (RMP), kanamycin (KM) and ofloxacin (OFX) for KMO medium were calibrated by comparing the minimal inhibitory concentrations (MICs) against clinical isolates of Mycobacterium tuberculosis on KMO with those on Löwenstein-Jensen (LJ). The performance of the direct KMO DST technique was evaluated on 186 smear-positive sputum specimens and compared with indirect LJ DST. Agreement of MICs on direct vs. indirect DST was high for INH, RMP and OFX. KM MICs on KMO were ∼10 g/ml higher than those on LJ. The critical concentrations of INH, RMP, OFX and KM for KMO were therefore set at 0.2, 40.0, 2.0, and 40.0 g/ml. The evaluation of direct DST of smear-positive sputum specimens showed 100% agreement with indirect LJ DST for INH and RMP. However, the respective susceptible and resistant predictive values were 98.8% and 100% for OFX, and 100% and 80% for KM. Direct DST using KMO is useful, with clear advantages of a shorter turnaround time, procedural simplicity and low cost compared to indirect DST. It may be most indicated in resource-poor settings for programmatic management of drug-resistant tuberculosis.

Routine immunization in Pakistan: comparison of multiple data sources and identification of factors associated with vaccination.

PubMed

Imran, Hafsa; Raja, Dania; Grassly, Nicholas C; Wadood, M Zubair; Safdar, Rana M; O'Reilly, Kathleen M

2018-03-01

Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010-2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Adjusted coverage of children 12-23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates.

Mutant prevention concentrations of four carbapenems against gram-negative rods.

PubMed

Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C

2010-06-01

We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ss-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to > or =16. The MPC/MIC ratios for beta-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 microg/ml) than those for ss-lactamase-negative strains.

Biocompatibility of designed MicNo-ZnO particles: Cytotoxicity, genotoxicity and phototoxicity in human skin keratinocyte cells.

PubMed

Genç, Hatice; Barutca, Banu; Koparal, A Tansu; Özöğüt, Uğurcan; Şahin, Yücel; Suvacı, Ender

2018-03-01

Recently, designed platelet shaped micron particles that are composed of nano primary particles, called MicNo (=Micron+naNo) particles, have been developed to exploit the benefits of nano size, while removing the adverse effects of nanoparticles. It has been shown that MicNo-ZnO particles exhibit both micron and nanosized particle characteristics. Although physical and chemical properties of MicNo-ZnO particles have been studied, their biocompatibility has not yet been evaluated. Accordingly, the research objective of this study was to evaluate in vitro cytotoxicity, genotoxicity and phototoxicity behaviors of designed MicNo-ZnO particles over human epidermal keratinocyte (HaCaT) cells. MicNo-ZnO particles exhibit much less cytotoxicity with IC 50 concentrations between 40 and 50μg/ml, genotoxicity above 40μg/ml and lower photo genotoxicity under UVA on HaCaT than the ZnO nanoparticles. Although their chemistries are the same, the source of this difference in toxicity values may be attributed to size differences between the particles that are probably due to their ability to penetrate into the cells. In the present study, the expansive and detailed in vitro toxicity tests show that the biocompatibility of MicNo-ZnO particles is much better than that of the ZnO nanoparticles. Consequently, MicNo-ZnO particles can be considered an important active ingredient alternative for sunscreen applications due to their safer characteristics with respect to ZnO nanoparticles. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro susceptibility of four antimicrobials against Riemerella anatipestifer isolates: a comparison of minimum inhibitory concentrations and mutant prevention concentrations for ceftiofur, cefquinome, florfenicol, and tilmicosin.

PubMed

Li, Yafei; Zhang, Yanan; Ding, Huanzhong; Mei, Xian; Liu, Wei; Zeng, Jiaxiong; Zeng, Zhenling

2016-11-09

Mutant prevention concentration (MPC) is an alternative pharmacodynamic parameter that has been used to measure antimicrobial activity and represents the propensities of antimicrobial agents to select resistant mutants. The concentration range between minimum inhibitory concentration (MIC) and MPC is defined as mutant selection window (MSW). The MPC and MSW parameters represent the ability of antimicrobial agents to inhibit the bacterial mutants selected. This study was conducted to determine the MIC and MPC values of four antimicrobials including ceftiofur, cefquinome, florfenicol and tilmicosin against 105 Riemerella anatipestifer isolates. The MIC 50 /MIC 90 values of clinical isolates tested in our study for ceftiofur, cefquinome, florfenicol and tilmicosin were 0.063/0.5、0.031/0.5、1/4、1/4 μg/mL, respectively; MPC 50 / MPC 90 values were 4/64、8/64、4/32、16/256 μg/mL, respectively. These results provided information on the use of these compounds in treating the R. anatipestifer infection; however, additional studies are needed to demonstrate their therapeutic efficacy. Based on the MSW theory, the hierarchy of these tested antimicrobial agents with respect to selecting resistant subpopulations was as follows: cefquinome > ceftiofur > tilmicosin > florfenicol. Cefquinome was the drug that presented the highest risk of selecting resistant mutant among the four antimicrobial agents.

Effectiveness of tilmicosin against Paenibacillus larvae, the causal agent of American Foulbrood disease of honeybees.

PubMed

Reynaldi, Francisco J; Albo, Graciela N; Alippi, Adriana M

2008-11-25

American Foulbrood (AFB) of honeybees (Apis mellifera L.), caused by the Gram-positive bacterium Paenibacillus larvae is one of the most serious diseases affecting the larval and pupal stages of honeybees (A. mellifera L.). The aim of the present work was to asses the response of 23 strains of P. larvae from diverse geographical origins to tilmicosin, a macrolide antibiotic developed for exclusive use in veterinary medicine, by means of the minimal inhibitory concentration (MIC) and the agar diffusion test (ADT). All the strains tested were highly susceptible to tilmicosin with MIC values ranging between 0.0625 and 0.5 microg ml(-1), and with MIC(50) and MIC(90) values of 0.250 microg ml(-1). The ADT tests results for 23 P. larvae strains tested showed that all were susceptible to tilmicosin with inhibition zones around 15 microg tilmicosin disks ranging between 21 and 50mm in diameter. Oral acute toxicity of tilmicosin was evaluated and the LD(50) values obtained demonstrated that it was virtually non-toxic for adult bees and also resulted non-toxic for larvae when compared with the normal brood mortality. Dosage of 1000 mg a.i. of tilmicosin applied in a 55 g candy resulted in a total suppression of AFB clinical signs in honeybee colonies 60 days after initial treatment. To our knowledge, this is the first report of the effectiveness of tilmicosin against P. larvae both in vitro and in vivo.

Potential application of synthesized ferrocenylimines compounds for the elimination of bacteria in water

NASA Astrophysics Data System (ADS)

Ikhile, M. I.; Barnard, T. G.; Ngila, J. C.

2017-08-01

This work reports a study towards a search for environmentally friendly water disinfectant. The most common method for water treatment is based on chlorine which had a wide application over the years as a water disinfectant, but suffer the disadvantage of reacting with natural organic matter to form disinfection by products. In this study, the potential application of novel ferrocenylimines compounds, namely 4-ferrocenylaniline (1), N-(3-bromo-2-hydroxylbenzylidene)-4-ferrocenylimine (2) and N-(3-bromo-5-chlorosalicyl)-4-ferrocenylimine (3) for the elimination of bacteria in water was investigated by evaluating their antibacterial properties against twelve different bacterial strains using microdilution method in sterile 96 well micro titer plates. The in vitro antibacterial activity revealed that the ferrocenylimines compound exhibit higher antibacterial activity than ferrocene, which is one of the starting materials towards the synthesis of this novel ferrocenylimines compounds. The most active ferrocenylimines compound was compound 3 with a minimal inhibitory concentration (MIC) value of 0.30 mg/ml against S. sonnei. In addition, all the ferrocenylimines compounds possessed excellent antibacterial activity against B. cereus with the same MIC value of 0.31 mg/ml. The results obtained so far show great potential in the three tested ferrocenylimines compounds for use in water treatment in killing bacteria in water.

Antibacterial activity of ethanolic extracts of some Vietnamese medicinal plants against Helicobacter pylori

NASA Astrophysics Data System (ADS)

Ngan, Luong Thi My; Dung, Pham Phuong; Nhi, Nguyen Vang Thi Yen; Hoang, Nguyen van Minh; Hieu, Tran Trung

2017-09-01

Helicobacter pylori is one of the most common human infectious bacteria. The infection is highly associated with a number of the most important disease of the upper gastrointestinal tract, including gastritis, duodenitis, peptic ulceration, and gastric cancer. In addition, widespread use of antimicrobial agents has resulted in the development of antibiotic resistance. Metabolites of plants, particularly higher plants, have been suggested as alternative potential sources for antibacterial products due to their safe. This study aimed to evaluate antibacterial activities of crude ethanolic extracts of seventeen Vietnamese medicinal plants toward one reference strain and three clinical isolates of Helicobacter pylori using broth micro-dilution bioassay. The antibacterial activities of these extracts were also compared with those of seven antibiotics, amoxicillin, clarithromycin, erythromycin, levofloxacin, azithromycin, tetracycline, and metronidazole. The extracts of Ampelopsis cantoniensis and Cleistocalyx operculatus showed highest antibacterial activity with MIC (MBC) values of 0.31 - 0.97 (2.5 - 5) mg/mL, followed by the extracts of Hedyotis diffusa and Ardisia silvestris with MIC (MBC) values of 1.04 - 1.94 (7.5 - 10) mg/mL. The remaining plant extracts exhibited moderate, low and very low or no active to the H. pylori strains. Further studies are needed to determine the active compounds from the extracts that showed high antibacterial activity against H. pylori.

Determination of moxifloxacin anaerobic susceptibility breakpoints according to the Clinical and Laboratory Standards Institute guidelines.

PubMed

Ambler, Jane; Rennie, Robert; Poupard, James; Koeth, Laura; Stass, Heino; Endermann, Rainer; Choudhri, Shurjeel

2008-05-01

A summary of the key data presented to Clinical and Laboratory Standards Institute (CLSI, formerly National Committee for Clinical and Laboratory Standards) in determination of moxifloxacin anaerobic breakpoints is presented. The breakpoint analysis required review of a variety of data, including bacteriologic and clinical outcomes by MIC of anaerobic isolates from prospective clinical trials in patients with complicated intra-abdominal infections, human and animal pharmacokinetic/pharmacodynamic (PK/PD) information and in vitro models, MIC distributions of indicated organisms, and animal model efficacy data for strains with MIC values around prospective breakpoints. The compilation of the various components of this breakpoint analysis supports the US Food and Drug Administration (FDA) and CLSI moxifloxacin anaerobic breakpoints of < or =2 mg/L (susceptible), 4 mg/L (intermediate), and > or =8 mg/L (resistant), and provides information to European investigators for interpretation of MICs prior to establishment of the European Committee on Antimicrobial Susceptibility Testing breakpoints.

Are Vancomycin Trough Concentrations of 15 to 20 mg/L Associated With Increased Attainment of an AUC/MIC ≥ 400 in Patients With Presumed MRSA Infection?

PubMed

Hale, Cory M; Seabury, Robert W; Steele, Jeffrey M; Darko, William; Miller, Christopher D

2017-06-01

To determine whether there is an association between higher vancomycin trough concentrations and attainment of a calculated area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ≥400. A retrospective analysis was conducted among vancomycin-treated adult patients with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. Attainment of a calculated AUC/MIC ≥400 was compared between patients with troughs in the reference range of 15 to 20 mg/L and those with troughs in the following ranges: <10, 10 to 14.9, and >20 mg/L. Nephrotoxicity was assessed as a secondary outcome based on corrected average vancomycin troughs over 10 days of treatment. Overall, 226 patients were reviewed and 100 included. Relative to troughs ≥10, patients with vancomycin troughs <10 mg/L were 73% less likely to attain an AUC/MIC ≥400 (odds ratio [OR] 0.27, 95% confidence interval [CI]: 0.01-0.75). No difference was found in the attainment of an AUC/MIC ≥400 in patients with troughs of 10 to 14.9 mg/L and >20 mg/L when compared to patients with troughs of 15 to 20 mg/L. The mean corrected average vancomycin trough was higher in patients developing nephrotoxicity compared to those who did not (19.5 vs 14.5 mg/L, P < .001). Achieving vancomycin serum trough concentrations of 15 to 20 mg/L did not result in an increased attainment of the AUC/MIC target relative to troughs of 10 to 14.9 mg/L but may increase nephrotoxicity risk.

Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in diagnosing benign and malignant disease of the pancreas.

PubMed

Kaur, Sukhwinder; Baine, Michael J; Guha, Sushovan; Ochi, Nobuo; Chakraborty, Subhankar; Mallya, Kavita; Thomas, Colleen; Crook, Julia; Wallace, Michael B; Woodward, Timothy A; Jain, Maneesh; Singh, Shailender; Sasson, Aaron R; Skinner, Verna; Raimondo, Massimo; Batra, Surinder K

2013-04-01

Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases. A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay. Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61-0.76). Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.

In vitro evaluation of the potential for resistance development to ceragenin CSA-13

PubMed Central

Pollard, Jake E.; Snarr, Jason; Chaudhary, Vinod; Jennings, Jacob D.; Shaw, Hannah; Christiansen, Bobbie; Wright, Jonathan; Jia, Wenyi; Bishop, Russell E.; Savage, Paul B.

2012-01-01

Objectives Though most bacteria remain susceptible to endogenous antimicrobial peptides, specific resistance mechanisms are known. As mimics of antimicrobial peptides, ceragenins were expected to retain antibacterial activity against Gram-positive and -negative bacteria, even after prolonged exposure. Serial passaging of bacteria to a lead ceragenin, CSA-13, was performed with representative pathogenic bacteria. Ciprofloxacin, vancomycin and colistin were used as comparators. The mechanisms of resistance in Gram-negative bacteria were elucidated. Methods Susceptible strains of Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii were serially exposed to CSA-13 and comparators for 30 passages. MIC values were monitored. Alterations in the Gram-negative bacterial membrane composition were characterized via mass spectrometry and the susceptibility of antimicrobial-peptide-resistant mutants to CSA-13 was evaluated. Results S. aureus became highly resistant to ciprofloxacin after <20 passages. After 30 passages, the MIC values of vancomycin and CSA-13 for S. aureus increased 9- and 3-fold, respectively. The Gram-negative organisms became highly resistant to ciprofloxacin after <20 passages. MIC values of colistin for P. aeruginosa and A. baumannii increased to ≥100 mg/L after 20 passages. MIC values of CSA-13 increased to ∼20–30 mg/L and plateaued over the course of the experiment. Bacteria resistant to CSA-13 displayed lipid A modifications that are found in organisms resistant to antimicrobial peptides. Conclusions CSA-13 retained potent antibacterial activity against S. aureus over the course of 30 serial passages. Resistance generated in Gram-negative bacteria correlates with modifications to the outer membranes of these organisms and was not stable outside of the presence of the antimicrobial. PMID:22899801

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

PubMed Central

Lei, Zhixin; Liu, Qianying; Yang, Bing; Ahmed, Saeed; Cao, Jiyue; He, Qigai

2018-01-01

The goal of this study was to establish the epidemiological, pharmacodynamic cut-off values, optimal dose regimens for tildipirosin against Haemophilus parasuis. The minimum inhibitory concentrations (MIC) of 164 HPS isolates were determined and SH0165 whose MIC (2 μg/ml ) were selected for PD analysis. The ex vivo MIC in plasma of SH0165 was 0.25 μg/ml which was 8 times lower than that in TSB. The bacteriostatic, bactericidal and elimination activity (AUC24h/MIC) in serum were 26.35, 52.27 and 73.29 h based on the inhibitory sigmoid Emax modeling. The present study demonstrates that 97.9% of the wild-type (WT) isolates were covered when the epidemiological cut-off value (ECV) was set at 8 μg/ml. The parameters including AUC24h, AUC, T1/2, Cmax, CLb and MRT in PELF were 19.56, 60.41, 2.32, 4.02, 56.6, and 2.63 times than those in plasma, respectively. Regarding the Monte Carlo simulation, the COPD was defined as 0.5 μg/ml in vitro, and the optimal doses to achieve bacteriostatic, bactericidal and elimination effect were 1.85, 3.67 and 5.16 mg/kg for 50% target, respectively, and 2.07, 4.17 and 5.78 mg/kg for 90% target, respectively. The results of this study offer a more optimised alternative for clinical use and demonstrated that 4.17 mg/kg of tildipirosin by intramuscular injection could have an effect on bactericidal activity against HPS. These values are of great significance for the effective treatment of HPS infections, but it also be deserved to be validated in clinical practice in the future research. PMID:29416722

Eimeria maxima microneme protein 2 delivered as DNA vaccine and recombinant protein induces immunity against experimental homogenous challenge.

PubMed

Huang, Jingwei; Zhang, Zhenchao; Li, Menghui; Song, Xiaokai; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui

2015-10-01

E. maxima is one of the seven species of Eimeria that infects chicken. Until now, only a few antigenic genes of E. maxima have been reported. In the present study, the immune protective effects against E. maxima challenge of recombinant protein and DNA vaccine encoding EmMIC2 were evaluated. Two-week-old chickens were randomly divided into five groups. The experimental group of chickens was immunized with 100 μg DNA vaccine pVAX1-MIC2 or 200 μg rEmMIC2 protein while the control group of chickens was injected with pVAX1 plasmid or sterile PBS. The results showed that the anti-EmMIC2 antibody titers of both rEmMIC2 protein and pVAX1-MIC2 groups were significantly higher as compared to PBS and pVAX1 control (P<0.05). The splenocytes from both vaccinated groups of chickens displayed significantly greater proliferation compared with the controls (P<0.05). Serum from chickens immunized with pVAX1-MIC2 and rEmMIC2 protein displayed significantly high levels of IL-2, IFN-γ, IL-10, IL-17, TGF-β and IL-4 (P<0.05) compared to those of negative controls. The challenge experiment results showed that both the recombinant protein and the DNA vaccine could obviously alleviate jejunum lesions, body weight loss, increase oocyst, decrease ratio and provide ACIs of more than 165. All the above results suggested that immunization with EmMIC2 was effective in imparting partial protection against E. maxima challenge and it could be an effective antigen candidate for the development of new vaccines against E. maxima. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mesoionic compounds with antifungal activity against Fusarium verticillioides.

PubMed

Paiva, Rojane de Oliveira; Kneipp, Lucimar Ferreira; dos Reis, Camilla Moretto; Echevarria, Aurea

2015-02-04

Fungi contaminate the food of humans and animals, are a risk to health, and can cause financial losses. In this work, the antifungal activities of 16 mesoionic compounds (MI 1-16) were evaluated against mycotoxigenic fungi, including Aspergillus spp., Fusarium verticillioides and Penicillium citrinum. Furthermore, the decreased ergosterol in the total lipid content of Fusarium verticillioides was investigated. F. verticillioides was the most sensitive fungus to the mesoionic compounds. Among the evaluated compounds, MI-11 and MI-16 presented higher antifungal effects against F. verticillioides, with MIC values of 7.8 μg/ml, and MI-2 and MI-3 followed, with MICs of 15.6 μg/ml. The most active compounds were those with heterocyclic ring phenyl groups substituted by electron donor moieties (MI-11 and MI-16). Among some compounds with higher activity (MI-2, MI-11 and MI-16), decreased ergosterol content in the total lipid fraction of F. verticillioides was demonstrated. MI-2 reduced the ergosterol content approximately 40% and 80% at concentrations of 7.8 μg/ml and 15.6 μg/ml, respectively, and MI-11 and MI-16 decreased the content by 30% and 50%, respectively, when at a concentration of 7.8 μg/ml. These findings indicate that mesoionic compounds have significant antifungal activity against F. verticillioides.

Antibacterial activity against Streptococcus mutans and diametrical tensile strength of an interim cement modified with zinc oxide nanoparticles and terpenes: An in vitro study.

PubMed

Andrade, Verónica; Martínez, Alejandra; Rojas, Ninón; Bello-Toledo, Helia; Flores, Paulo; Sánchez-Sanhueza, Gabriela; Catalán, Alfonso

2018-05-01

Interim restorations are occasionally left in the mouth for extended periods and are susceptible to bacterial infiltration. Thus, dental interim cements with antibacterial properties are required. The purpose of this in vitro study was to determine in vitro antibacterial activity against Streptococcus mutans and to compare the diametrical tensile strength (DTSs) of dental interim cement modified with zinc oxide nanoparticles (ZnO-NPs) with that of cement modified with terpenes. Antibacterial properties of ZnO-NPs, terpenes, and dental interim cement modified with ZnO-NPs and cement modified with terpenes against S mutans were tested according to minimum inhibitory concentration (MIC) and direct contact inhibition (DCI). Tensile strength levels were evaluated using DTS. Results were analyzed using the Kolmogorov-Smirnov, ANOVA, and Tamhane tests (α=.05). The MICs of ZnO-NPs and terpenes against S mutans were 61.94 μg/g and 0.25% v/v, respectively. The DCI assay under the cylinders of cement (area of contact with the agar surface) revealed significant bacterial growth inhibition on Temp-Bond NE specimens with ZnO-NPs at MIC of 495.2 μg/g (8× MIC) and with terpenes at MIC 0.999% v/v (4× MIC) (P<.05). The Temp-Bond NE cement cylinder (control group) showed the lowest DTS (1.05 ±0.27 MPa) of all other test groups. In the Zn-NPs group, the greatest increase occurred in the NP8 (8× MIC; 495.2 μg/g) group with a value of 1.50 ±0.23 MPa, a significant increase in DTS compared with the control and terpene groups (P<.05). In the terpene group, the highest increase corresponded to group T2 (2× MIC; 0.4995% v/v) with a value of 1.29 ±0.18 MPa. The addition of terpenes and ZnO-NPs to interim cement showed antibacterial activity when in contact with S. mutans ATCC 25175. Both terpenes and ZnO-NPs antimicrobial agents increased diametral tensile strength. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Chemical composition and antifungal activity of the essential oil of Origanum virens on Candida species.

PubMed

Salgueiro, L R; Cavaleiro, C; Pinto, E; Pina-Vaz, C; Rodrigues, A G; Palmeira, A; Tavares, C; Costa-de-Oliveira, S; Gonçalves, M J; Martinez-de-Oliveira, J

2003-09-01

The composition and the antifungal activity of the essential oil of Origanum virens on Candida species were studied. The essential oil was obtained from the aerial parts of the plant by hydrodistillation and analyzed by GC and GC-MS. The oil was characterized by its high content of carvacrol (68.1 %) and its biogenetic precursors, gamma-terpinene (9.9 %) and p-cymene (4.5 %). The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity against Candida strains (7 clinical isolates and 3 ATCC type strains). The inhibition of germ tube formation and flow cytometry, using the fluorescent probe propidium iodide (PI), were used to evaluate their mechanisms of action. MIC and MLC values were similar for most tested strains, ranging from 0.16 to 0.32 microL/mL. Concentrations lower than MIC values strongly prevent germ tube formation. The fungicidal effect is primarily due to an extensive lesion of the membrane.

Chemical compositions and antimicrobial activities of Athrixia phylicoides DC. (bush tea), Monsonia burkeana (special tea) and synergistic effects of both combined herbal teas.

PubMed

Tshivhandekano, Itani; Ntushelo, Khayalethu; Ngezimana, Wonder; Tshikalange, Thilivhali Emmanuel; Mudau, Fhatuwani Nixwell

2014-09-01

To determine the chemical compositions and evaluate the antimicrobial activity of bush tea (Athrixia phylicoides DC.), special tea (Monsonia burkeana) and synergy (combination of bush tea and special tea). Total polyphenols were determined using the methods reported by Singleton and Rossi (1965) and modified by Waterman and Mole (1994). Tannins were determined using vanillin HCL methods described by Prince et al. (1978). Total antioxidants were determined using the methods described by Awika et al. (2004). The micro dilution technique using 96-well micro-plates, as described by Eloff (1998) was used to obtain the minimum inhibition concentration (MIC) and minimum microbicidal concentration (MMC) values of the ethanol extracts against the microorganisms under study. The microbes strain used was Gram negative bacteria such as Escherichia coli, Klebsiella oxytoca, Proteus vulgaris, Serratia marcescens, Salmonella typhi, Klebsiella pneumonia; Gram positive bacteria such as Bacillus cereus, Staphylococcus aureus and a fungus Candida albicans. The results demonstrated that special tea contains significantly higher content of total polyphenols (8.34 mg/100 g) and total antioxidant (0.83 mg/100 g) as compared to bush tea [total polyphenols (6.41 mg/100g) and total antioxidant (0.63 mg/100g)] and combination of bush tea and special tea [total polyphenols (6.42 mg/100 g) and total antioxidant (0.64 mg/100 g)]. There was no significant difference in tannins between bush tea, special tea and synergy. The results of antimicrobial activity (MIC and MMC) demonstrated that the ethanol extracts of bush tea, special tea and synergy possessed antimicrobial activity against all microorganisms at different zones. The MIC of bush tea ranged from 1.56 to 12.50 mg/mL while the MMC ranged from 0.78 to 12.50 mg/mL. Special tea's MIC ranged from 0.39 to 12.50 mg/mL while the MMC ranged from 0.01 to 12.50 mg/mL. The MIC of synergy ranged from 3.13 to 12.50 mg/mL while the MMC ranged from 3.13 to 12.50 mg/mL without positive synergistic effect recorded. Both bush and special tea contain total polyphenols, total antioxidants and tannins with special tea containing a significantly higher total polyphenols and total antioxidant as compared to bush tea and synergy. Bush tea, special tea and synergy possess antimicrobial activity at various degrees. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales

PubMed Central

Chakrabarti, A.; Chowdhary, A.; Cordoba, S.; Dannaoui, E.; Dufresne, P.; Fothergill, A.; Ghannoum, M.; Gonzalez, G. M.; Guarro, J.; Kidd, S.; Lass-Flörl, C.; Meis, J. F.; Pelaez, T.; Tortorano, A. M.; Turnidge, J.

2015-01-01

Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 μg/ml, those for M. circinelloides were 1 and 2 μg/ml, those for R. arrhizus were 2 and 4 μg/ml, and those for R. microsporus were 2 and 2 μg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated. PMID:25583714

Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales.

PubMed

Espinel-Ingroff, A; Chakrabarti, A; Chowdhary, A; Cordoba, S; Dannaoui, E; Dufresne, P; Fothergill, A; Ghannoum, M; Gonzalez, G M; Guarro, J; Kidd, S; Lass-Flörl, C; Meis, J F; Pelaez, T; Tortorano, A M; Turnidge, J

2015-03-01

Clinical breakpoints (CBPs) have not been established for the Mucorales and any antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales species. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) were defined with available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada, Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10 Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus, 146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs comprising ≥95% and ≥97.5% of the modeled populations were as follows: amphotericin B ECVs for L. corymbifera were 1 and 2 μg/ml, those for M. circinelloides were 1 and 2 μg/ml, those for R. arrhizus were 2 and 4 μg/ml, and those for R. microsporus were 2 and 2 μg/ml, respectively; posaconazole ECVs for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2, respectively; both itraconazole ECVs for R. arrhizus were 2 μg/ml. ECVs may aid in detecting emerging resistance or isolates with reduced susceptibility (non-WT MICs) to the agents evaluated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Development of cross-resistance by Aspergillus fumigatus to clinical azoles following exposure to prochloraz, an agricultural azole

PubMed Central

2014-01-01

Background The purpose of this study was to unveil whether azole antifungals used in agriculture, similar to the clinical azoles used in humans, can evoke resistance among relevant human pathogens like Aspergillus fumigatus, an ubiquitous agent in nature. Additionally, cross-resistance with clinical azoles was investigated. Antifungal susceptibility testing of environmental and clinical isolates of A. fumigatus was performed according to the CLSI M38-A2 protocol. In vitro induction assays were conducted involving daily incubation of susceptible A. fumigatus isolates, at 35°C and 180 rpm, in fresh GYEP broth medium supplemented with Prochloraz (PCZ), a potent agricultural antifungal, for a period of 30 days. Minimal inhibitory concentrations (MIC) of PCZ and clinical azoles were monitored every ten days. In order to assess the stability of the developed MIC, the strains were afterwards sub-cultured for an additional 30 days in the absence of antifungal. Along the in vitro induction process, microscopic and macroscopic cultural observations were registered. Results MIC of PCZ increased 256 times after the initial exposure; cross-resistance to all tested clinical azoles was observed. The new MIC value of agricultural and of clinical azoles maintained stable in the absence of the selective PCZ pressure. PCZ exposure was also associated to morphological colony changes: macroscopically the colonies became mostly white, losing the typical pigmentation; microscopic examination revealed the absence of conidiation. Conclusions PCZ exposure induced Aspergillus fumigatus morphological changes and an evident increase of MIC value to PCZ as well as the development of cross-resistance with posaconazole, itraconazole and voriconazole. PMID:24920078

Pharmacokinetic Modeling and Limited Sampling Strategies Based on Healthy Volunteers for Monitoring of Ertapenem in Patients with Multidrug-Resistant Tuberculosis.

PubMed

van Rijn, S P; Zuur, M A; van Altena, R; Akkerman, O W; Proost, J H; de Lange, W C M; Kerstjens, H A M; Touw, D J; van der Werf, T S; Kosterink, J G W; Alffenaar, J W C

2017-04-01

Ertapenem is a broad-spectrum carbapenem antibiotic whose activity against Mycobacterium tuberculosis is being explored. Carbapenems have antibacterial activity when the plasma concentration exceeds the MIC at least 40% of the time (40% T MIC ). To assess the 40% T MIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on data for healthy volunteers. A two-compartment population pharmacokinetic model was developed with data for 42 healthy volunteers using an iterative two-stage Bayesian method. External validation was performed by Bayesian fitting of the model developed with data for volunteers to the data for individual MDR-TB patients (in which the fitted values of the area under the concentration-time curve from 0 to 24 h [AUC 0-24, fit values] were used) using the population model developed for volunteers as a prior. A Monte Carlo simulation ( n = 1,000) was used to evaluate limited sampling strategies. Additionally, the 40% T MIC with the free fraction ( f 40% T MIC ) of ertapenem in MDR-TB patients was estimated with the population pharmacokinetic model. The population pharmacokinetic model that was developed was shown to overestimate the area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) in MDR-TB patients by 6.8% (range, -17.2 to 30.7%). The best-performing limited sampling strategy, which had a time restriction of 0 to 6 h, was found to be sampling at 1 and 5 h ( r 2 = 0.78, mean prediction error = -0.33%, root mean square error = 5.5%). Drug exposure was overestimated by a mean percentage of 4.2% (range, -15.2 to 23.6%). When a free fraction of 5% was considered and the MIC was set at 0.5 mg/liter, the minimum f 40% T MIC would have been exceeded in 9 out of 12 patients. A population pharmacokinetic model and limited sampling strategy, developed using data from healthy volunteers, were shown to be adequate to predict ertapenem exposure in MDR-TB patients. Copyright © 2017 American Society for Microbiology.

Inhibition of Listeria monocytogenes by food antimicrobials applied singly and in combination.

PubMed

Brandt, Alex L; Castillo, Alejandro; Harris, Kerri B; Keeton, Jimmy T; Hardin, Margaret D; Taylor, Thomas M

2010-01-01

Combining food antimicrobials can enhance inhibition of Listeria monocytogenes in ready-to-eat (RTE) meats. A broth dilution assay was used to compare the inhibition of L. monocytogenes resulting from exposure to nisin, acidic calcium sulfate, ε-poly-L-lysine, and lauric arginate ester applied singly and in combination. Minimum inhibitory concentrations (MICs) were the lowest concentrations of single antimicrobials producing inhibition following 24 h incubation at 35 °C. Minimum bactericidal concentrations (MBCs) were the lowest concentrations that decreased populations by ≥3.0 log(10) CFU/mL. Combinations of nisin with acidic calcium sulfate, nisin with lauric arginate ester, and ɛ-poly-L-lysine with acidic calcium sulfate were prepared using a checkerboard assay to determine optimal inhibitory combinations (OICs). Fractional inhibitory concentrations (FICs) were calculated from OICs and were used to create FIC indices (FIC(I)s) and isobolograms to classify combinations as synergistic (FIC(I) < 1.00), additive/indifferent (FIC(I)= 1.00), or antagonistic (FIC(I) > 1.00). MIC values for nisin ranged from 3.13 to 6.25 μg/g with MBC values at 6.25 μg/g for all strains except for Natl. Animal Disease Center (NADC) 2045. MIC values for ε-poly-L-lysine ranged from 6.25 to 12.50 μg/g with MBCs from 12.50 to 25.00 μg/g. Lauric arginate ester at 12.50 μg/g was the MIC and MBC for all strains; 12.50 mL/L was the MIC and MBC for acidic calcium sulfate. Combining nisin with acidic calcium sulfate synergistically inhibited L. monocytogenes; nisin with lauric arginate ester produced additive-type inhibition, while ε-poly-L-lysine with acidic calcium sulfate produced antagonistic-type inhibition. Applying nisin along with acidic calcium sulfate should be further investigated for efficacy on RTE meat surfaces. © 2010 Institute of Food Technologists®

Occurrence of porphyromonas gingivalis and its antibacterial susceptibility to metronidazole and tetracycline in patients with chronic periodontitis.

PubMed

Gamboa, Fredy; Acosta, Adriana; García, Dabeiba-Adriana; Velosa, Juliana; Araya, Natalia; Ledergerber, Roberto

2014-01-01

Chronic periodontitis is a multifactorial infectious disease associated with Gram-negative strict anaerobes which are immersed in the subgingival biofilm. Porphyromonas gingivalis, an important periodontal pathogen, is frequently detected in patients with chronic periodontitis. Although isolates of P. gingivalis tend to be susceptible to most antimicrobial agents, relatively little information is available on its in vitro antimicrobial susceptibility. The aim of this study was to determine the frequency of P. gingivalis in patients with chronic periodontitis and to assess antimicrobial susceptibility in terms of minimum inhibitory concentration (MIC) of clinical isolates to metronidazole and tetracycline. A descriptive, observational study was performed including 87 patients with chronic periodontitis. Samples were taken from the periodontal pocket using paper points, which were placed in thioglycollate broth. Samples were incubated for 4 hours at 37°C in anaerobic conditions and finally replated on Wilkins-Chalgren anaerobic agar (Oxoid). Bacteria were identified using the RapIDTMANAII system (Remel) and antimicrobial susceptibility was determined with the M.I.C. Evaluator test (MICE, Oxoid). P. gingivalis was identified in 30 of the 87 patients with chronic periodontitis, which represents a frequency of 34.5%. All 30 isolates (100%) were sensitive to metronidazole, with MIC values ranging from 0015-4ug/ml. Regarding tetracycline, 27 isolates (90%) were sensitive, with MIC values ranging from <0.015 to 4 ug /ml, the remaining three isolates (10%) were resistant to tetracycline with MIC values of 8ug/ ml. There was no statistically significant difference in age, gender, pocket depth, clinical attachment level and severity of periodontitis between the group of patients with chronic periodontitis and P. gingivalis and the group of patients with chronic periodontitis without P. gingivalis. In conclusion, P. gingivalis was found at a frequency of 34.5% in patients with chronic periodontitis and clinical isolates were highly sensitive to metronidazole and tetracycline.

Effects of intramuscularly administered enrofloxacin on the susceptibility of commensal intestinal Escherichia coli in pigs (sus scrofa domestica).

PubMed

Römer, Antje; Scherz, Gesine; Reupke, Saskia; Meißner, Jessica; Wallmann, Jürgen; Kietzmann, Manfred; Kaspar, Heike

2017-12-04

In the European Union, various fluoroquinolones are authorised for the treatment of food producing animals. Each administration poses an increased risk of development and spread of antimicrobial resistance. The aim of this study was to investigate the impact of parenteral administration of enrofloxacin on the prevalence of enrofloxacin and ciprofloxacin susceptibilities in the commensal intestinal E. coli population. E. coli isolates from faeces of twelve healthy pigs were included. Six pigs were administered enrofloxacin on day 1 to 3 and after two weeks for further three days. The other pigs formed the control group. MIC values were determined. Virulence and resistance genes were detected by PCR. Phylogenetic grouping was performed by PCR. Enrofloxacin and ciprofloxacin were analysed in sedimentation samples by HPLC. Susceptibility shifts in commensal E. coli isolates were determined in both groups. Non-wildtype E. coli could be cultivated from two animals of the experimental group for the first time one week after the first administration and from one animal of the control group on day 28. The environmental load with enrofloxacin in sedimentation samples showed the highest amount between days one and five. The repeated parenteral administration of enrofloxacin to pigs resulted in rapidly increased MIC values (day 28: MIC up to 4 mg/L, day 35: MIC ≥ 32mg/L). E. coli populations of the control group in the same stable without direct contact to the experimental group were affected. The parenteral administration of enrofloxacin to piglets considerably reduced the number of the susceptible intestinal E. coli population which was replaced by E. coli strains with increased MIC values against enrofloxacin. Subsequently also pigs of the control were affected suggesting a transferability of strains from the experimental group through the environment to the control group especially as we could isolate the same PFGE strains from both pig groups and the environment.

Mutant Prevention Concentrations of Four Carbapenems against Gram-Negative Rods▿ †

PubMed Central

Credito, Kim; Kosowska-Shick, Klaudia; Appelbaum, Peter C.

2010-01-01

We tested the propensities of four carbapenems to select for resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii mutants by determining the mutant prevention concentrations (MPCs) for 100 clinical strains with various ß-lactam phenotypes. Among the members of the Enterobacteriaceae family and A. baumannii strains, the MPC/MIC ratios were mostly 2 to 4. In contrast, for P. aeruginosa the MPC/MIC ratios were 4 to ≥16. The MPC/MIC ratios for β-lactamase-positive K. pneumoniae and E. coli isolates were much higher (range, 4 to >16 μg/ml) than those for ß-lactamase-negative strains. PMID:20308376

Comparative antimicrobial characterization of LBM415 (NVP PDF-713), a new peptide deformylase inhibitor of clinical importance.

PubMed

Fritsche, Thomas R; Sader, Helio S; Cleeland, Roy; Jones, Ronald N

2005-04-01

LBM415 (NVP PDF-713) is the first member of the peptide deformylase (PDF) inhibitor class being developed for clinical trials as a parenteral and oral agent for treatment of community-acquired respiratory tract disease and serious infections caused by antimicrobial-resistant gram-positive cocci. In this study susceptibility testing results from 1,306 recent clinical isolates selected to over-represent resistance trends among the species were summarized. All staphylococci (153 strains; MIC at which 90% of isolates were inhibited [MIC90], 2 microg/ml), Streptococcus pneumoniae (170 strains; MIC90, 1 microg/ml), other streptococci (150 strains; MIC90, 1 microg/ml), enterococci (104 strains; MIC90, 4 microg/ml), Moraxella catarrhalis (103 strains; MIC90, 0.5 microg/ml), and Legionella pneumophila (50 strains; MIC90, 0.12 microg/ml) were inhibited at < or = 8 microg of LBM415/ml, as were 97% of Haemophilus influenzae isolates (300 strains; MIC90, 4 to 8 microg/ml). Among other bacterial groups, 100% of gram-positive and -negative anaerobes, including 22 Bacteroides spp. strains (31 strains total; MIC90, 1 microg/ml), were inhibited by < or = 4 microg/ml, whereas Enterobacteriaceae (112 strains) and most nonfermentative bacilli (107 strains) were not inhibited at readily achievable concentrations. The compound was found to have a dominantly bacteriostatic action, and spontaneous single-step mutational rates occurred at low levels (10(-6) to <10(-8)). Drug interaction studies failed to identify any class-specific synergistic interactions, nor were antagonistic interactions observed. Variations in broth and agar MIC test conditions demonstrated that, whereas the agar-based method trended towards a 1-log2 dilution-higher MIC than the broth method and was inoculum dependent, other variations in incubation environment, medium supplements, pH, or calcium concentration had little influence on LBM415 MIC results. Use of the efflux inhibitor phe-arg-beta-naphthylamide showed an average of 1 log2 dilution decrease in H. influenzae MICs, demonstrating the contribution of efflux pumps in influencing susceptibility to PDF inhibitors. The in vitro activity of LBM415 against targeted bacterial species, including resistant subsets, and other laboratory characteristics of this novel compound demonstrate the potential of PDF inhibitors as a new class of antimicrobial agents.

In vitro activity of a polyhexanide-betaine solution against high-risk clones of multidrug-resistant nosocomial pathogens.

PubMed

López-Rojas, Rafael; Fernández-Cuenca, Felipe; Serrano-Rocha, Lara; Pascual, Álvaro

2017-01-01

To determine the in vitro activity of a polyhexanide-betaine solution against collection strains and multidrug-resistant (MDR) nosocomial isolates, including high-risk clones. We studied of 8 ATCC and 21 MDR clinical strains of Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, including the multiresistant high-risk clones. The MICs and MBCs of a 0.1% polyhexanide-0.1% betaine solution were determined by microdilution. For each species, strains with the highest MICs were selected for further experiments. The dilution-neutralization test (PrEN 12054) was performed by incubating bacterial inocula of 10 6 CFU/mL for 1min with undiluted 0.1% polyhexanide-betaine solution. The CFUs were counted after neutralization. Growth curves and time-kill curves at concentrations of 0.25, 1, 4, and 8×MIC, were performed. MICs of recovered strains were determined when regrowth was observed in time-kill studies after 24h of incubation. Strains with reduced susceptibility were selected by serial passage on plates with increasing concentrations of polyhexanide-betaine, and MICs were determined. Polyhexanide-betaine MIC range was 0.5-8mg/L. MBCs equalled or were 1 dilution higher than MICs. The dilution-neutralization method showed total inoculum clearance of all strains. In time-kill curves, no regrowth was observed at 4×MIC, except for S. aureus (8×MIC). Increased MICs were not observed in time-kill curves, or after serial passages after exposure to polyhexanide-betaine. Polyhexanide-betaine presented bactericidal activity against all MDR clinical isolates tested, including high-risk clones, at significantly lower concentrations and time of activity than those commercially used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Antibacterial Effects of Levofloxacin, Erythromycin, and Rifampin in a Human Monocyte System against Legionella pneumophila

PubMed Central

Baltch, Aldona L.; Smith, Raymond P.; Franke, Mary A.; Michelsen, Phyllis B.

1998-01-01

The antibacterial activities of levofloxacin, erythromycin, and rifampin against intracellular Legionella pneumophila L-1033, serogroup 1, were studied. In an in vitro system utilizing adherent human monocytes, L. pneumophila L-1033, a phagocytosis time period of 1 h, and antibiotic (levofloxacin, erythromycin, and/or rifampin) at 1 to 10 times the MIC, the CFU/ml values for the monocyte lysate were determined during 0- to 4-day time periods. The decrease in CFU/ml with levofloxacin at pH 7.4 was rapid, occurring within 24 h, and was drug concentration dependent (P < 0.01). The decrease in CFU with rifampin was first observed at 48 h (P < 0.01), while only a minimal decrease in CFU/ml was observed with erythromycin. Combination of levofloxacin and rifampin and of levofloxacin and erythromycin at ten times their MICs significantly decreased the CFU/ml value (P < 0.01), to the value attained by levofloxacin alone, while combination of rifampin and erythromycin did not. Removal of levofloxacin after 24 h of incubation resulted in regrowth of L. pneumophila L-1033, while a continued slow decrease in CFU/ml was seen following rifampin removal; CFU/ml values were unaffected by the removal of erythromycin. At 4 days, and even in assays performed following antibiotic removal, the CFU/ml value continued to be lower in the levofloxacin and rifampin assays than in the assays with erythromycin. Levofloxacin had a significantly higher bactericidal activity against L. pneumophila L-1033 than erythromycin or rifampin. In these assays, the addition of erythromycin or rifampin did not affect the antibacterial activity of levofloxacin. PMID:9835507

In vitro susceptibility of Borrelia burgdorferi isolates to three antibiotics commonly used for treating equine Lyme disease.

PubMed

Caol, Sanjie; Divers, Thomas; Crisman, Mark; Chang, Yung-Fu

2017-09-29

Lyme disease in humans is predominantly treated with tetracycline, macrolides or beta lactam antibiotics that have low minimum inhibitory concentrations (MIC) against Borrelia burgdorferi. Horses with Lyme disease may require long-term treatment making frequent intravenous or intramuscular treatment difficult and when administered orally those drugs may have either a high incidence of side effects or have poor bioavailability. The aim of the present study was to determine the in vitro susceptibility of three B. burgdorferi isolates to three antibiotics of different classes that are commonly used in practice for treating Borrelia infections in horses. Broth microdilution assays were used to determine minimum inhibitory concentration of three antibiotics (ceftiofur sodium, minocycline and metronidazole), for three Borrelia burgdorferi isolates. Barbour-Stoner-Kelly (BSK K + R) medium with a final inoculum of 10 6 Borrelia cells/mL and incubation periods of 72 h were used in the determination of MICs. Observed MICs indicated that all isolates had similar susceptibility to each drug but susceptibility to the tested antimicrobial agents varied; ceftiofur sodium (MIC = 0.08 μg/ml), minocycline hydrochloride (MIC = 0.8 μg/ml) and metronidazole (MIC = 50 μg/ml). The MIC against B. burgorferi varied among the three antibiotics with ceftiofur having the lowest MIC and metronidazole the highest MIC. The MIC values observed for ceftiofur in the study fall within the range of reported serum and tissue concentrations for the drug metabolite following ceftiofur sodium administration as crystalline-free acid. Minocycline and metronidazole treatments, as currently used in equine practice, could fall short of attaining MIC concentrations for B. burgdorferi.

Chemical composition and anti-biofilm activity of Thymus sipyleus BOISS. subsp. sipyleus BOISS. var. davisianus RONNIGER essential oil.

PubMed

Ceylan, Ozgur; Ugur, Aysel

2015-06-01

In this study, antimicrobial and antibiofilm activities and the chemical composition of Thymus sipyleus BOISS. subsp. sipyleus BOISS. var. davisianus RONNIGER essential oil was evaluated. The essential oil was obtained by hydro-distillation and analyzed by gas chromatography-mass spectrometry. Fourteen compounds were characterized, having as major components thymol (38.31%) and carvacrol (37.95%). Minimum inhibitory concentrations (MICs) of oil and the major components were calculated by serial dilution method, and anti-biofilm effects by microplate biofilm assay against five Gram positive (Staphylococcus aureus MU 38, MU 40, MU 46, MU 47, Stahylococcus epidermidis MU 30) and five Gram negative (Pseudomonas aeruginosa MU 187, MU 188, MU 189, Pseudomonas fluorescens MU 180, MU 181) bacteria. It was found that MICs for essential oil, thymol and carvacrol were between 5 and 50 µl/ml, 0.125-0.5 µg/ml and 0.125-05 µl/ml, respectively. The results showed that doses of MIC produced a greater anti-biofilm influence than 0.5, 0.25 and 0.125 MIC. In the presence of essential oil (MIC), the mean biofilm formation value was equal to 67 ± 5.5% for P. aeruginosa MU 188, and essential oil (MIC) inhibition exceeds 60% for P. aeruginosa biofilms. The results also showed that carvacrol (MIC) was able to induce an inhibition 72.9 ± 4.1% for S.aureus (MU 40) biofilm. In addition, thymol (MIC) showed 68.6 ± 5.3% reduction in biofilm formation of P. fluorescens MU 181. This study demonstrated the antimicrobial and antibiofilm activity of T. sipyleus BOISS. subsp. sipyleus BOISS. var. davisianus RONNIGER essential oil and points out the exceptional efficiency of thymol and carvacrol, which could represent candidates in the treatment of Pseudomonas and Staphylococcus biofilms.

Jacaranda cuspidifolia Mart. (Bignoniaceae) as an antibacterial agent.

PubMed

Arruda, Ana Lúcia A; Vieira, Carla J B; Sousa, Daniella G; Oliveira, Regilene F; Castilho, Rachel O

2011-12-01

This study evaluated, in vitro, the antimicrobial activity of the hexane extract (JCHE), methanol extract (JCME), and chloroform fraction (JCCF) of bark from Jacaranda cuspidifolia Mart. (Family Bignoniaceae), a Brazilian medicinal plant, traditionally used as anti-syphilis and anti-gonorrhea treatment. The antimicrobial activity was evaluated using the disc diffusion method followed by the determination of minimum inhibitory concentration (MIC) values. JCHE was not active against the bacteria evaluated. JCME presented antibacterial activity against Streptococcus pyogenes, Staphylococcus aureus, and Neisseria gonorrhoeae with MIC values of 16.3 mg/mL, 9.1 mg/mL, and 25.2 mg/mL, respectively. JCCF was active against Staphylococcus epidermidis, S. aureus, Proteus mirabilis, Serratia marcescens, S. pyogenes, Enterobacter aerogenes, and N. gonorrhoeae with MIC values of 18.3 mg/mL, 9.3 mg/mL, 6.3 mg/mL, 6.1 mg/mL, 9.2 mg/mL, 6.2 mg/mL, and 25.2 mg/mL, respectively. Phytochemical analysis of JCME and JCCF gave positive results for saponins, coumarins, flavonoids, tannins, quinones, alkaloids, triterpenes, and steroids. Verbascoside was isolated and identified as a major peak in JCME and JCCF high-performance liquid chromatography fingerprints and might contribute to the observed antimicrobial activity.

[Fundamental studies on legionellosis--the growth with in Acanthamoeba sp. and antibiotics susceptibility of Legionella spp. isolated from soil samples in Japan].

PubMed

Furuhata, Katsunori; Miyamoto, Hiroshi; Hara, Motonobu; Fukuyama, Masafumi

2003-02-01

As part of an epidemiological study of legionellosis, we investigated the growth within Acanthamoeba sp. and antibiotic susceptibility of 62 strains of Legionella spp. isolated from surface soils nationwide in 2001. 1) All strains tested grew in Acanthamoeba sp., suggesting that the strains were pathogenic. The minimum bacterial number required for the growth in the amoeba was 10(3)-10(8) CFU/ml and there were differences between the strains. 2) Susceptibility to 10 drugs was investigated using the Etest. The MIC90 values of imipenem, as a beta-lactam, and rifampicin, as an antitubercular agent, were 0.047 microgram/ml and 0.064 microgram/ml, respectively, showing high sensitivity. In contrast, sensitivity to minocycline, as a tetracycline, and piperacillin, as a beta-lactam, was low and the MIC90 values were 12 micrograms/ml and 16 micrograms/ml, respectively. Sensitivity to minocycline was particularly low, with a MIC value of 32 micrograms/ml, in two strains. The above findings suggested that all soil-derived strains were pathogenic, and susceptibility of the strains tended to be slightly lower than that of clinical isolates.

Short communication: Interaction of the isomers carvacrol and thymol with the antibiotics doxycycline and tilmicosin: In vitro effects against pathogenic bacteria commonly found in the respiratory tract of calves.

PubMed

Kissels, W; Wu, X; Santos, R R

2017-02-01

Bovine respiratory disease is the major problem faced by cattle, specially calves, leading to reduced animal performance and increased mortality, consequently causing important economic losses. Hence, calves must be submitted to antibiotic therapy to counteract this infection usually initiated by the combination of environmental stress factors and viral infection, altering the animal's defense mechanism, and thus allowing lung colonization by the opportunistic bacteria Mannheimia haemolytica and Pasteurella multocida. Essential oils appear to be candidates to replace antibiotics or to act as antibiotic adjuvants due to their antimicrobial properties. In the present study, we aimed to evaluate the 4 essential oil components carvacrol, thymol, trans-anethole, and 1,8 cineole as antibacterial agents or as adjuvants for the antibiotics doxycycline and tilmicosin against M. haemolytica and P. multocida. Bacteria were cultured according to standard protocols, followed by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration. A checkerboard assay was applied to detect possible interactions between components, between antibiotics, and between components and antibiotics. Doxycycline at 0.25 and 0.125 μg/mL inhibited the growth of P. multocida and M. haemolytica, respectively, whereas tilmicosin MIC values were 1.0 and 4.0 μg/mL for P. multocida and M. haemolytica, respectively. Carvacrol MIC values were 2.5 and 1.25 mM for P. multocida and M. haemolytica, respectively, whereas thymol MIC values were 1.25 and 0.625 mM for P. multocida and M. haemolytica, respectively. Trans-anethole and 1,8 cineole did not present any antibacterial effect even at 40 mM against the investigated pathogens. All minimum bactericidal concentration values were the same as MIC, except when thymol was tested against M. haemolytica, being twice the MIC data (i.e., 1.25 mM thymol). Based on fractional inhibitory concentration checkerboard assay, no interaction was observed between doxycycline and tilmicosin. Carvacrol and thymol presented an additive effect when one of them was combined with tilmicosin. Additive effect was also observed when doxycycline was combined with thymol. Synergism was observed when carvacrol was combined with doxycycline or with thymol. Although the antibacterial effects of the tested essential oil components were observed at high concentrations for in vitro conditions, the additive and synergic effects of carvacrol and thymol with antibiotics suggest the option to apply them as antibiotic adjuvants. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparison of methods for in vitro testing of susceptibility of porcine Mycoplasma species to antimicrobial agents.

PubMed

Ter Laak, E A; Pijpers, A; Noordergraaf, J H; Schoevers, E C; Verheijden, J H

1991-02-01

The MICs of 18 antimicrobial agents used against strains of three porcine Mycoplasma species were determined by a serial broth dilution method. Twenty field strains of M. hyorhinis, ten field strains of M. hyopneumoniae, six field strains of M. flocculare, and the type strains of these species were tested. Twelve field strains and the type strain of M. hyorhinis were also tested by an agar dilution method. Tests were read at various time points. When the broth dilution method was used, the final MIC had to be read 2 days after color changes had stopped. MICs of tetracycline, oxytetracycline, doxycycline, and minocycline were low for the three Mycoplasma species tested. MICs of chlortetracycline were 8 to 16 times higher than MICs of the other tetracyclines. Spiramycin, tylosin, kitasamycin, spectinomycin, tiamulin, lincomycin, and clindamycin were effective against all strains of M. hyorhinis and M. hyopneumoniae. The quinolones were highly effective against M. hyopneumoniae but less effective against M. hyorhinis. The susceptibility patterns for M. hyopneumoniae and M. flocculare were similar.

Comparison of methods for in vitro testing of susceptibility of porcine Mycoplasma species to antimicrobial agents.

PubMed Central

Ter Laak, E A; Pijpers, A; Noordergraaf, J H; Schoevers, E C; Verheijden, J H

1991-01-01

The MICs of 18 antimicrobial agents used against strains of three porcine Mycoplasma species were determined by a serial broth dilution method. Twenty field strains of M. hyorhinis, ten field strains of M. hyopneumoniae, six field strains of M. flocculare, and the type strains of these species were tested. Twelve field strains and the type strain of M. hyorhinis were also tested by an agar dilution method. Tests were read at various time points. When the broth dilution method was used, the final MIC had to be read 2 days after color changes had stopped. MICs of tetracycline, oxytetracycline, doxycycline, and minocycline were low for the three Mycoplasma species tested. MICs of chlortetracycline were 8 to 16 times higher than MICs of the other tetracyclines. Spiramycin, tylosin, kitasamycin, spectinomycin, tiamulin, lincomycin, and clindamycin were effective against all strains of M. hyorhinis and M. hyopneumoniae. The quinolones were highly effective against M. hyopneumoniae but less effective against M. hyorhinis. The susceptibility patterns for M. hyopneumoniae and M. flocculare were similar. PMID:2024954

Activity of Deferasirox in Mucorales: Influences of Species and Exogenous Iron▿

PubMed Central

Lewis, Russell E.; Pongas, Georgios N.; Albert, Nathaniel; Ben-Ami, Ronen; Walsh, Thomas J.; Kontoyiannis, Dimitrios P.

2011-01-01

Differences in deferasirox susceptibility among members of the order Mucorales are unknown. Here we show that Cunninghamella bertholletiae (four isolates) and Mucor species (five isolates) display higher deferasirox MICs and minimal fungicidal concentrations compared to Rhizopus species (six isolates). Exogenous iron further attenuated the deferasirox susceptibility of Mucorales isolates with low MICs. Vital staining revealed damage to subapical compartments in susceptible strains. PMID:20956598

Activity of deferasirox in Mucorales: influences of species and exogenous iron.

PubMed

Lewis, Russell E; Pongas, Georgios N; Albert, Nathaniel; Ben-Ami, Ronen; Walsh, Thomas J; Kontoyiannis, Dimitrios P

2011-01-01

Differences in deferasirox susceptibility among members of the order Mucorales are unknown. Here we show that Cunninghamella bertholletiae (four isolates) and Mucor species (five isolates) display higher deferasirox MICs and minimal fungicidal concentrations compared to Rhizopus species (six isolates). Exogenous iron further attenuated the deferasirox susceptibility of Mucorales isolates with low MICs. Vital staining revealed damage to subapical compartments in susceptible strains.

Improved detection of Candida sp. fks hot spot mutants by using the method of the CLSI M27-A3 document with the addition of bovine serum albumin.

PubMed

Garcia-Effron, Guillermo; Park, Steven; Perlin, David S

2011-05-01

Echinocandins are highly bound to serum proteins, altering their antifungal properties. The addition of 50% human serum to the MIC assay improves the identification of echinocandin-resistant Candida spp. harboring fks hot spot mutations. However, this modification cannot readily be applied to the method of the CLSI M27-A3 document due to safety and standardization difficulties. The aim of this study was to evaluate commercial bovine serum albumin (BSA) as a safe and standardized alternative to human serum. A collection of 28 echinocandin-susceptible strains, 10 Candida parapsilosis sensu lato strains (with naturally reduced echinocandin susceptibility), and 40 FKS hot spot mutants was used in this work. When RPMI 1640 was used for susceptibility testing, wild-type strains and fks mutants showed MIC range overlaps (-2, -1, and -3 2-fold-dilution steps separated these populations for anidulafungin, caspofungin, and micafungin, respectively). On the other hand, the addition of BSA to RPMI 1640 differentially increased echinocandin MIC values for these groups of strains, allowing better separation between populations, with no MIC range overlaps for any of the echinocandin drugs tested. Moreover, the use of RPMI-BSA reduced the number of fks hot spot mutant isolates for which MIC values were less than or equal to the upper limit for the wild type (very major errors) from 9, 2, and 7 with RPMI alone to 3, 0, and 3 for anidulafungin, caspofungin, and micafungin, respectively. When RPMI-BSA was used to study the susceptibility of C. parapsilosis sensu lato species to echinocandins, the strains behaved as anidulafungin- and micafungin-resistant isolates (MIC, ≥8 μg/ml). These data support the need for a revision of the CLSI protocol for in vitro testing of echinocandin susceptibility in order to identify all or most of the fks hot spot mutants. Also, caspofungin could be used as a surrogate marker of reduced susceptibility to echinocandins.

In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration

PubMed Central

Jiang, Zhi-Dong; Ke, Shi; Palazzini, Ernesto; Riopel, Lise; Dupont, Herbert

2000-01-01

Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates tested were inhibited = 50 μg/ml) for 145 bacterial enteropathogens from patients with traveler's diarrhea acquired in Mexico during the summers of 1997 and 1998. Rifaximin concentrations in stool the day after oral administration (800 mg daily for 3 days) were high (average, 7,961 μg/g), proving the value of the drug. PMID:10898704

Comparative efficacy of tilmicosin versus tulathromycin as a metaphylactic antimicrobial in feedlot calves at moderate risk for respiratory disease.

PubMed

Van Donkersgoed, Joyce; Merrill, John; Hendrick, Steven

2008-01-01

The purpose of this study was to compare the efficacy and cost-effectiveness of tilmicosin (MIC) versus tulathromycin (DRAX) as a metaphylactic antimicrobial in feedlot calves at moderate risk for bovine respiratory disease (BRD). Calves that received DRAX had significantly (P < or = .05) lower initial BRD treatment rates compared with calves that received MIC. However, there were no significant differences in the BRD relapse rate, railer rate, total mortality rate, BRD mortality rate, average daily gain, and dry matter conversion between the two groups. The economic advantage of the MIC group was Can$8.29/animal. Based on these results, while DRAX was more efficacious in reducing initial treatments for BRD in feedlot calves at moderate risk for disease, MIC was more cost-effective. The lower initial BRD treatment costs in the DRAX group did not offset the higher metaphylactic cost of DRAX.

Ceftaroline fosamil salvage therapy: an option for reduced-vancomycin-susceptible MRSA bacteraemia.

PubMed

Espedido, Björn A; Jensen, Slade O; van Hal, Sebastiaan J

2015-03-01

To examine the activity of ceftaroline against reduced-vancomycin-susceptible MRSA isolates. One-hundred and three MRSA blood culture isolates (predominantly ST239-MRSA-III), with varying vancomycin phenotypes, had their ceftaroline MICs determined by broth microdilution and MIC Evaluator strip (Oxoid-Thermo Fisher). Statistical analyses were performed that examined relationships with vancomycin and daptomycin MICs. Mutations in mecA were also examined. All 103 isolates (including 60 heteroresistant vancomycin-intermediate Staphylococcus aureus/vancomycin-intermediate S. aureus) were susceptible to ceftaroline, with one isolate displaying heteroresistance that may be related to a mecA mutation. Higher ceftaroline MICs were associated with vancomycin-susceptible S. aureus isolates. This study highlights that ceftaroline fosamil is an option for salvage therapy based on in vitro activity. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

In vitro activity of bergamot natural essence and furocoumarin-free and distilled extracts, and their associations with boric acid, against clinical yeast isolates.

PubMed

Romano, L; Battaglia, F; Masucci, L; Sanguinetti, M; Posteraro, B; Plotti, G; Zanetti, S; Fadda, G

2005-01-01

There is very little information, to date, on the antifungal activity of bergamot oil. In this study, we investigated the in vitro activity of three bergamot oils (natural essence, furocoumarin-free extract and distilled extract) against clinically relevant Candida species. We studied the two derivatives, components of Italian pharmaceutical products, that are supposed to be less toxic than the essential oil. In vitro susceptibility of 40 clinical isolates of Candida spp. (Candida albicans, n=20; Candida glabrata, n=13; Candida krusei, n=4; Candida tropicalis, n=2; Candida parapsilosis, n=1), associated with symptomatic and asymptomatic vulvovaginal candidiasis, was determined using a modification of the NCCLS M27-A2 broth microdilution method. MICs were evaluated for each of the oils alone and combined with sub-inhibitory concentrations of the well-known antiseptic, boric acid. To boric acid, all isolates had MIC values ranging from 0.094% to 0.187% (w/v). At 24 h readings, the MIC(90 )s (for all isolates) were (v/v): 5% for natural essence of bergamot, 2.5% for the furocoumarin-free extract, and 1.25% for the distilled extract. At the 48 h reading, these values increased to >10%, 5% and 2.5%, respectively. At both readings, MIC(90 )s for all oil+boric acid combinations were significantly lower than corresponding values for the oils alone (P <0.05). These data indicate that bergamot oils are active in vitro against Candida spp., suggesting their potential role for the topical treatment of Candida infections.

Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis.

PubMed

Garvey, E P; Hoekstra, W J; Schotzinger, R J; Sobel, J D; Lilly, E A; Fidel, P L

2015-09-01

Vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) remain major health problems for women. VT-1161, a novel fungal CYP51 inhibitor which has potent antifungal activity against fluconazole-sensitive Candida albicans, retained its in vitro potency (MIC50 of ≤0.015 and MIC90 of 0.12 μg/ml) against 10 clinical isolates from VVC or RVVC patients resistant to fluconazole (MIC50 of 8 and MIC90 of 64 μg/ml). VT-1161 pharmacokinetics in mice displayed a high volume of distribution (1.4 liters/kg), high oral absorption (73%), and a long half-life (>48 h) and showed rapid penetration into vaginal tissue. In a murine model of vaginal candidiasis using fluconazole-sensitive yeast, oral doses as low as 4 mg/kg VT-1161 significantly reduced the fungal burden 1 and 4 days posttreatment (P < 0.0001). Similar VT-1161 efficacy was measured when an isolate highly resistant to fluconazole (MIC of 64 μg/ml) but fully sensitive in vitro to VT-1161 was used. When an isolate partially sensitive to VT-1161 (MIC of 0.12 μg/ml) and moderately resistant to fluconazole (MIC of 8 μg/ml) was used, VT-1161 remained efficacious, whereas fluconazole was efficacious on day 1 but did not sustain efficacy 4 days posttreatment. Both agents were inactive in treating an infection with an isolate that demonstrated weaker potency (MICs of 2 and 64 μg/ml for VT-1161 and fluconazole, respectively). Finally, the plasma concentrations of free VT-1161 were predictive of efficacy when in excess of the in vitro MIC values. These data support the clinical development of VT-1161 as a potentially more efficacious treatment for VVC and RVVC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer.

PubMed

Skipworth, R J E; Deans, D A C; Tan, B H L; Sangster, K; Paterson-Brown, S; Brown, D A; Hunter, M; Breit, S N; Ross, J A; Fearon, K C H

2010-02-16

Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of > or =10 mg l(-1) or modified Glasgow prognostic score (mGPS) of > or =1), and nutritional status were assessed in newly diagnosed OGC patients (n=293). Healthy volunteers (n=35) served as controls. MIC-1 was elevated in patients (median=1371 pg ml(-1); range 141-39 053) when compared with controls (median=377 pg ml(-1); range 141-3786; P<0.001). Patients with gastric tumours (median=1592 pg ml(-1); range 141-12 643) showed higher MIC-1 concentrations than patients with junctional (median=1337 pg ml(-1); range 383-39 053) and oesophageal tumours (median=1180 pg ml(-1); range 258-31 184; P=0.015). Patients showed a median weight loss of 6.4% (range 0.0-33.4%), and 42% of patients had an mGPS of > or =1 or plasma CRP of > or =10 mg l(-1) (median=9 mg l(-1); range 1-200). MIC-1 correlated positively with disease stage (r(2)=0.217; P<0.001), age (r(2)=0.332; P<0.001), CRP (r(2)=0.314; P<0.001), and mGPS (r(2)=0.336; P<0.001), and negatively with Karnofsky Performance Score (r(2)=-0.269; P<0.001). However, although MIC-1 correlated weakly with dietary intake (r(2)=0.157; P=0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median=204 days; 95% CI 157-251) when compared with patients with MIC-1 levels in the lower three quartiles (median=316 days; 95% CI 259-373; P=0.036), but MIC-1 was not an independent prognostic indicator. There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

Antimicrobial activity of fresh garlic juice: An in vitro study

PubMed Central

Yadav, Seema; Trivedi, Niyati A.; Bhatt, Jagat D.

2015-01-01

Introduction: Antimicrobial resistance has been a global concern. Currently, interest has been focused on exploring antimicrobial properties of plants and herbs. One such botanical is Allium sativum (garlic). Aim: To evaluate the antimicrobial activity of fresh juice of garlic. Materials and Methods: Varying concentrations of fresh garlic juice (FGJ) were tested for their antimicrobial activity against common pathogenic organisms isolated at SSG Hospital, Vadodara, using well diffusion method. Moreover, minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) of FGJ were tested using broth dilution method. Sensitivity pattern of the conventional antimicrobials against common pathogenic bacteria was tested using disc diffusion method. Results: FGJ produced dose-dependent increase in the zone of inhibition at a concentration of 10% and higher. MIC of FGJ against the pathogens ranged from 4% to 16% v/v whereas MLC value ranged from 4% to 32% v/v with Escherichia coli and Staphylococcus aureus spp. showed highest sensitivity. Conclusion: FGJ has definite antimicrobial activity against common pathogenic organisms isolated at SSG Hospital, Vadodara. Further studies are needed to find out the efficacy, safety, and kinetic data of its active ingredients. PMID:27011724

In vitro antimicrobial activity of extracts and isolated compound from Dalbergia stipulacea Roxb. leaves

NASA Astrophysics Data System (ADS)

Kumar, Arvind; Bhat, Tahir Ahmad; Singh, Rattan Deep

2017-07-01

The study was designed to examine the in vitro antimicrobial efficacy of extracts and isolated compound of Dalbergia stipulacea. Combined extracts (chloroform and methanol) of plant leaves fractionated with n-butanol loaded with column afforded a flavonoid glycoside compound identified as luteolin 4'-rutinoside. Different extracts and isolated compound exhibited pronounced antibacterial and antifungal varied activities against four bacteria (Clostridium acetobutylinium, Bacillus subtilis, Streptococcus mutans, and Pseudomonas sp.) and one fungus (Candida albicans) susceptibility were determined using disc diffusion method. The minimum inhibitory concentration (MIC) of extracts and isolated compounds was determined by broth dilution method. The maximum activity was shown by chloroform extract against C. albicans with a zone of inhibition of 17 mm and minimum activity was displayed by methanolic extract against Pseudomonas sp. with 5 mm. However, isolated compound has shown maximum activity against Pseudomonas sp. with 15 mm. The MIC values higher in methanol extract against Pseudomonas sp. and isolated compound shows good against Pseudomonas sp. and B. subtilis. Our findings indicate that plant could be used as a good antimicrobial agent in food, pharmaceutical and bio-pesticide industries.

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

PubMed Central

Singh, Pradeep Kumar; Kathuria, Shallu

2015-01-01

We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted. PMID:26438489

Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance.

PubMed

Boyanova, Lyudmila; Evstatiev, Ivailo; Gergova, Galina; Yaneva, Penka; Mitov, Ivan

2015-12-01

Only a few studies have evaluated Helicobacter pylori susceptibility to linezolid. The aim of the present study was to assess linezolid susceptibility in H. pylori, including strains with double/multidrug resistance. The susceptibility of 53 H. pylori strains was evaluated by Etest and a breakpoint susceptibility testing method. Helicobacter pylori resistance rates were as follows: amoxicillin, 1.9%; metronidazole, 37.7%; clarithromycin, 17.0%; tetracycline, 1.9%; levofloxacin, 24.5%; and linezolid (>4 mg/L), 39.6%. The linezolid MIC50 value was 31.2-fold higher than that of clarithromycin and 10.5-fold higher than that of levofloxacin; however, 4 of 11 strains with double/multidrug resistance were linezolid-susceptible. The MIC range of the oxazolidinone agent was larger (0.125-64 mg/L) compared with those in the previous two reports. The linezolid resistance rate was 2.2-fold higher in metronidazole-resistant strains and in strains resistant to at least one antibiotic compared with the remaining strains. Briefly, linezolid was less active against H. pylori compared with clarithromycin and levofloxacin, and linezolid resistance was linked to resistance to metronidazole as well as to resistance to at least one antibiotic. However, linezolid activity against some strains with double/multidrug resistance may render the agent appropriate to treat some associated H. pylori infections following in vitro susceptibility testing of the strains. Clinical trials are required to confirm this suggestion. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Screening of Trichoderma isolates for their potential of biosorption of nickel and cadmium.

PubMed

Nongmaithem, Nabakishor; Roy, Ayon; Bhattacharya, Prateek Madhab

2016-01-01

Fourteen Trichoderma isolates were evaluated for their tolerance to two heavy metals, nickel and cadmium. Three isolates, MT-4, UBT-18, and IBT-I, showed high levels of nickel tolerance, whereas MT-4, UBT-18, and IBT-II showed better tolerance of cadmium than the other isolates. Under nickel stress, biomass production increased up to a Ni concentration of 60ppm in all strains but then decreased as the concentrations of nickel were further increased. Among the nickel-tolerant isolates, UBT-18 produced significantly higher biomass upon exposure to nickel (up to 150ppm); however, the minimum concentration of nickel required to inhibit 50% of growth (MIC50) was highest in IBT-I. Among the cadmium-tolerant isolates, IBT-II showed both maximum biomass production and a maximum MIC50 value in cadmium stress. As the biomass of the Trichoderma isolates increased, a higher percentage of nickel removal was observed up to a concentration of 40ppm, followed by an increase in residual nickel and a decrease in biomass production at higher nickel concentrations in the medium. The increase in cadmium concentrations resulted in a decrease in biomass production and positively correlated with an increase in residual cadmium in the culture broth. Nickel and cadmium stress also influenced the sensitivity of the Trichoderma isolates to soil fungistasis. Isolates IBT-I and UBT-18 were most tolerant to fungistasis under nickel and cadmium stress, respectively. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline free acid) in the ball python (Python regius).

PubMed

Adkesson, Michael J; Fernandez-Varon, Emilio; Cox, Sherry; Martín-Jiménez, Tomás

2011-09-01

The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required.

Routine immunization in Pakistan: comparison of multiple data sources and identification of factors associated with vaccination

PubMed Central

Imran, Hafsa; Raja, Dania; Grassly, Nicholas C; Wadood, M Zubair; Safdar, Rana M; O’Reilly, Kathleen M

2018-01-01

Abstract Background Within Pakistan, estimates of vaccination coverage with the pentavalent vaccine, oral polio vaccine (OPV) and measles vaccine (MV) in 2011 were reported to be 74%, 75% and 53%, respectively. These national estimates may mask regional variation. The reasons for this variation have not been explored. Methods Data from the Multiple Indicator Cluster Surveys (MICS) for Balochistan and Punjab (2010–2011) are analysed to examine factors associated with receiving three or more doses of the pentavalent vaccine and one or more MVs using regression modelling. Pentavalent and OPV estimates from the MICS were compared to vaccine dose histories from surveillance for acute flaccid paralysis (AFP; poliomyelitis) to ascertain agreement. Results Adjusted coverage of children 12–23 months of age were estimated to be 16.0%, 75.5% and 34.2% in Balochistan and 58.0%, 87.7% and 72.6% in Punjab for the pentavalent vaccine, OPV and MV, respectively. Maternal education, healthcare utilization and wealth were associated with receiving the pentavalent vaccine and the MV. There was a strong correlation of district estimates of vaccination coverage between AFP and MICS data, but AFP estimates of pentavalent coverage in Punjab were biased toward higher values. Conclusions National estimates mask variation and estimates from individual surveys should be considered alongside other estimates. The development of strategies targeted towards poorly educated parents within low-wealth quintiles that may not typically access healthcare could improve vaccination rates. PMID:29432552

Significant antibacterial activity and synergistic effects of camel lactoferrin with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).

PubMed

Redwan, Elrashdy M; El-Baky, Nawal Abd; Al-Hejin, Ahmed M; Baeshen, Mohammed N; Almehdar, Hussein A; Elsaway, Abdulrahman; Gomaa, Abu-Bakr M; Al-Masaudi, Saad Berki; Al-Fassi, Fahad A; AbuZeid, Isam Eldin; Uversky, Vladimir N

2016-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) causes major healthcare problems in many countries, as it is present as several hospital- and community-associated strains. Hospital-associated MRSA is one of the most prevalent nosocomial pathogens throughout the world and infections caused by community-acquired MRSA are rising. This emphasizes the need for new and efficient anti-MRSA agents. We evaluated the antibacterial effects of camel lactoferrin (cLf) and human lactoferrin (hLf) alone and in combination with several antibiotics against MRSA. Antimicrobials were tested against MRSA and an S. aureus control strain by the agar disc diffusion method. The minimum inhibitory concentration (MIC) was determined for antimicrobials by the broth microdilution method. Synergy between cLf or hLf and antibiotics was examined by checkerboard and time-kill assays. The agar disc diffusion assay showed that MRSA growth was inhibited by cLf at 0.25-3 mg/ml and hLf at 1-3 mg/ml. cLf demonstrated 3 times higher inhibitory activity against MRSA than hLf in terms of MIC values (250 vs. 750 μg/ml, respectively). Biotinylated cLf was recognized by two membrane proteins of MRSA, 66-67 KDa. Combinations of cLf or hLf and oxacillin or vancomycin at sub-MIC levels enhanced in vitro antibacterial activity against MRSA compared with each agent alone. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?

PubMed

Leibovitz, Z; Daniel-Spiegel, E; Malinger, G; Haratz, K; Tamarkin, M; Gindes, L; Schreiber, L; Ben-Sira, L; Lev, D; Shapiro, I; Bakry, H; Weizman, B; Zreik, A; Egenburg, S; Arad, A; Tepper, R; Kidron, D; Lerman-Sagie, T

2016-05-01

To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction. Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history. Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively. The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Pharmacodynamic Evaluation and PK/PD-Based Dose Prediction of Tulathromycin: A Potential New Indication for Streptococcus suis Infection.

PubMed

Zhou, Yu-Feng; Peng, Hui-Min; Bu, Ming-Xiao; Liu, Ya-Hong; Sun, Jian; Liao, Xiao-Ping

2017-01-01

Tulathromycin is the first member of the triamilide antimicrobial drugs that has been registered in more than 30 countries. The goal of this study is to provide a potential new indication of tulathromycin for Streptococcus suis infections. We investigated the pharmacokinetic and ex vivo pharmacodynamics of tulathromycin against experimental S. suis infection in piglets. Tulathromycin demonstrated a relatively long elimination half-life (74.1 h) and a mean residence time of 97.6 h after a single intramuscular administration. The minimal inhibitory concentration (MIC) and bactericidal concentration in serum were markedly lower than those in broth culture, with Mueller-Hinton broth/serum ratios of 40.3 and 11.4, respectively. The post-antibiotic effects were at 1.27 h (1× MIC) and 2.03 h (4× MIC) and the post-antibiotic sub-MIC effect values ranged from 2.47 to 3.10 h. The ratio of the area under the concentration-time curve divided by the MIC (AUC/MIC) correlated well with the ex vivo antimicrobial effectiveness of tulathromycin ( R 2 = 0.9711). The calculated AUC 12h /MIC ratios in serum required to produce the net bacterial stasis, 1-log 10 and 2-log 10 killing activities were 9.62, 18.9, and 32.7, respectively. Based on the results of Monte Carlo simulation, a dosage regimen of 3.56 mg/kg tulathromycin was estimated to be effective, achieving for a bacteriostatic activity against S. suis infection over 5 days period. Tulathromycin may become a potential option for the treatment of S. suis infections.

Pharmacodynamic Evaluation and PK/PD-Based Dose Prediction of Tulathromycin: A Potential New Indication for Streptococcus suis Infection

PubMed Central

Zhou, Yu-Feng; Peng, Hui-Min; Bu, Ming-Xiao; Liu, Ya-Hong; Sun, Jian; Liao, Xiao-Ping

2017-01-01

Tulathromycin is the first member of the triamilide antimicrobial drugs that has been registered in more than 30 countries. The goal of this study is to provide a potential new indication of tulathromycin for Streptococcus suis infections. We investigated the pharmacokinetic and ex vivo pharmacodynamics of tulathromycin against experimental S. suis infection in piglets. Tulathromycin demonstrated a relatively long elimination half-life (74.1 h) and a mean residence time of 97.6 h after a single intramuscular administration. The minimal inhibitory concentration (MIC) and bactericidal concentration in serum were markedly lower than those in broth culture, with Mueller–Hinton broth/serum ratios of 40.3 and 11.4, respectively. The post-antibiotic effects were at 1.27 h (1× MIC) and 2.03 h (4× MIC) and the post-antibiotic sub-MIC effect values ranged from 2.47 to 3.10 h. The ratio of the area under the concentration–time curve divided by the MIC (AUC/MIC) correlated well with the ex vivo antimicrobial effectiveness of tulathromycin (R2 = 0.9711). The calculated AUC12h/MIC ratios in serum required to produce the net bacterial stasis, 1-log10 and 2-log10 killing activities were 9.62, 18.9, and 32.7, respectively. Based on the results of Monte Carlo simulation, a dosage regimen of 3.56 mg/kg tulathromycin was estimated to be effective, achieving for a bacteriostatic activity against S. suis infection over 5 days period. Tulathromycin may become a potential option for the treatment of S. suis infections. PMID:29033841

Antimicrobial activity of ceftaroline and comparator agents when tested against numerous species of coagulase-negative Staphylococcus causing infection in US hospitals.

PubMed

Sader, Helio S; Farrell, David J; Flamm, Robert K; Streit, Jennifer M; Mendes, Rodrigo E; Jones, Ronald N

2016-05-01

A total of 1593 coagulase-negative staphylococci (CoNS) considered clinically significant were collected from 71 US medical centers in 2013-2014 and tested for susceptibility by CLSI broth microdilution methods. Species identification was performed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Overall, 59.7% of isolates were oxacillin resistant (MRCoNS). Ceftaroline (MIC50/90, 0.25/0.5μg/mL) inhibited 99.2% of CoNS at ≤1μg/mL (susceptible breakpoint for Staphylococcus aureus), including 98.7% of MRCoNS, and the highest ceftaroline MIC value was 2μg/mL (13 isolates). Staphylococcus epidermidis represented 60.3% of the CoNS collection and was highly susceptible to ceftaroline (MIC50/90, 0.25/0.5μg/mL, 99.9% inhibited at ≤1μg/mL). All isolates of Staphylococcus capitis, Staphylococcus caprae, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pettenkoferi, Staphylococcus simulans, and Staphylococcus warneri (MIC50/90, 0.06-0.25/0.25-0.5μg/mL) were inhibited at ceftaroline MIC of ≤1μg/mL. Staphylococcus haemolyticus represented only 4.8%, was atypically less susceptible to ceftaroline (MIC50/90, 0.5/2μg/mL, 87.0% inhibited at ≤1μg/mL), and accounted for 76.9% (10/13) of isolates with ceftaroline MIC >1μg/mL. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron Corrosion Induced by Nonhydrogenotrophic Nitrate-Reducing Prolixibacter sp. Strain MIC1-1

PubMed Central

Ito, Kimio; Wakai, Satoshi; Tsurumaru, Hirohito; Ohkuma, Moriya; Harayama, Shigeaki

2014-01-01

Microbiologically influenced corrosion (MIC) of metallic materials imposes a heavy economic burden. The mechanism of MIC of metallic iron (Fe0) under anaerobic conditions is usually explained as the consumption of cathodic hydrogen by hydrogenotrophic microorganisms that accelerates anodic Fe0 oxidation. In this study, we describe Fe0 corrosion induced by a nonhydrogenotrophic nitrate-reducing bacterium called MIC1-1, which was isolated from a crude-oil sample collected at an oil well in Akita, Japan. This strain requires specific electron donor-acceptor combinations and an organic carbon source to grow. For example, the strain grew anaerobically on nitrate as a sole electron acceptor with pyruvate as a carbon source and Fe0 as the sole electron donor. In addition, ferrous ion and l-cysteine served as electron donors, whereas molecular hydrogen did not. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MIC1-1 was a member of the genus Prolixibacter in the order Bacteroidales. Thus, Prolixibacter sp. strain MIC1-1 is the first Fe0-corroding representative belonging to the phylum Bacteroidetes. Under anaerobic conditions, Prolixibacter sp. MIC1-1 corroded Fe0 concomitantly with nitrate reduction, and the amount of iron dissolved by the strain was six times higher than that in an aseptic control. Scanning electron microscopy analyses revealed that microscopic crystals of FePO4 developed on the surface of the Fe0 foils, and a layer of FeCO3 covered the FePO4 crystals. We propose that cells of Prolixibacter sp. MIC1-1 accept electrons directly from Fe0 to reduce nitrate. PMID:25548048

Concentration-Dependent Antagonism and Culture Conversion in Pulmonary Tuberculosis

PubMed Central

Pasipanodya, Jotam G.; Denti, Paolo; Sirgel, Frederick; Lesosky, Maia; Gumbo, Tawanda; Meintjes, Graeme; McIlleron, Helen; Wilkinson, Robert J.

2017-01-01

Abstract Background. There is scant evidence to support target drug exposures for optimal tuberculosis outcomes. We therefore assessed whether pharmacokinetic/pharmacodynamic (PK/PD) parameters could predict 2-month culture conversion. Methods. One hundred patients with pulmonary tuberculosis (65% human immunodeficiency virus coinfected) were intensively sampled to determine rifampicin, isoniazid, and pyrazinamide plasma concentrations after 7–8 weeks of therapy, and PK parameters determined using nonlinear mixed-effects models. Detailed clinical data and sputum for culture were collected at baseline, 2 months, and 5–6 months. Minimum inhibitory concentrations (MICs) were determined on baseline isolates. Multivariate logistic regression and the assumption-free multivariate adaptive regression splines (MARS) were used to identify clinical and PK/PD predictors of 2-month culture conversion. Potential PK/PD predictors included 0- to 24-hour area under the curve (AUC0-24), maximum concentration (Cmax), AUC0-24/MIC, Cmax/MIC, and percentage of time that concentrations persisted above the MIC (%TMIC). Results. Twenty-six percent of patients had Cmax of rifampicin <8 mg/L, pyrazinamide <35 mg/L, and isoniazid <3 mg/L. No relationship was found between PK exposures and 2-month culture conversion using multivariate logistic regression after adjusting for MIC. However, MARS identified negative interactions between isoniazid Cmax and rifampicin Cmax/MIC ratio on 2-month culture conversion. If isoniazid Cmax was <4.6 mg/L and rifampicin Cmax/MIC <28, the isoniazid concentration had an antagonistic effect on culture conversion. For patients with isoniazid Cmax >4.6 mg/L, higher isoniazid exposures were associated with improved rates of culture conversion. Conclusions. PK/PD analyses using MARS identified isoniazid Cmax and rifampicin Cmax/MIC thresholds below which there is concentration-dependent antagonism that reduces 2-month sputum culture conversion. PMID:28205671

Stability of Non-Neutral Plasma Cylinder Consisting of Magnetized Cold Electrons and of Small Density Fraction of Ions Born at Rest: Non-Local Analysis

NASA Astrophysics Data System (ADS)

Yeliseyev, Y. N.

2009-03-01

The non-local stability problem of the plasma cylinder, filled with "cold" magnetized rigidly rotating electrons, and a small density fraction of ions, is solved. The ions are supposed to be born at rest by ionization of background gas. The study is based on the kinetic description of ions. The equilibrium distribution function, taking into account the peculiarity of ions birth, is used. The radial electric field is caused by space charge of non-neutral plasma. The dispersion equation for plasma eigen frequencies is obtained analytically. It is valid within the total admissible range of values of electric and magnetic fields. Normalized eigen frequencies ω'/Ωi are calculated for the basic azimuth mode m = 1 (ω' = ω-mωi+, ω+ = (-ωci+Ωi)/2, Ωi = (ωci2-4eEr/mir)1/2 is called the "modified" ion cyclotron (MIC) frequency), for the density fraction of ions of atomic nitrogen f = Ni/ne = 0,01 and are presented in graphic form versus parameter 2ωpe2/ωce2. The spectra of oscillations ω'/Ωi consist of the family of electron Trivel-piece—Gould (TG) modes and of the families of MIC modes. The frequencies of MIC modes are located in a small vicinity of harmonics of the MIC frequency Ωi above and below the harmonic. The TG modes in non-neutral plasma fall in the region of MIC frequencies Ωi and interact strongly with MIC modes. The slow TG modes become unstable near the crossings with non-negative harmonics of MIC frequencies. The instabilities have a resonant character. The lowest radial TG mode has a maximum growth rate at crossing with a zero harmonic of Ωi ((Im ω'/Ωi)max≈0,074). The growth rates of MIC modes are much lower ((Im ω'/Ωi)max≲0,002). Their instability has a threshold character. The instabilities of TG and MIC modes take place mainly at the values of parameter 2ωpe2/ωce2, corresponding to strong radial electric fields (ωci2≪|eEr/mir|), in which the ions are unmagnetized. The oscillations of small amplitude are seen on some frequency dependencies of MIC modes. They are similar to oscillations on dispersion curves of electron waves in metals and are caused by the similarity between the ion equilibrium distribution function and the degenerate Fermi—Dirac one. The results obtained give the solution to the stability problem discussed by R.H. Levy, J.D. Daugherty and O. Buneman [Phys. Fl. 12, 2616-2629 (1969)] for a special case of plasma bounding directly with metal casing and possessing the volumetric eigen modes only.

Risk of Fungemia Due to Rhodotorula and Antifungal Susceptibility Testing of Rhodotorula Isolates

PubMed Central

Zaas, Aimee K.; Boyce, Molly; Schell, Wiley; Lodge, Barbara Alexander; Miller, Jackie L.; Perfect, John R.

2003-01-01

Rhodotorula infections occur among patients with immunosuppression and/or central venous catheters. Using standardized methods (NCCLS M27-A), we determined the antifungal susceptibilities of 10 Rhodotorula bloodstream infection isolates. Patient information was collected for clinical correlation. The MICs of amphotericin B and posaconazole were the lowest, and the MICs of triazoles and echinocandins were higher than those of other antifungal agents. PMID:14605170

Anti-MRSA cephalosporins Bristol-Myers Squibb.

PubMed

Johnson, A P

2001-02-01

BMS is investigating a series of cephalosporins for potential use in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection [274213]. In vitro activity tests resulted in a minimum inhibitory concentration (MIC) of 1 to 8 microg/ml against MRSA 1274213]. A series of C(3) benzoyloxymethyl cephalosporins exhibited in vitro activity against MRSA and methicillin-susceptible Staphylococcus aureus (MSSA), with MIC values ranging from 0.007 to 2 microM, and improved in vivo stability in human plasma [258890].

Azole susceptibility of Malassezia pachydermatis and Malassezia furfur and tentative epidemiological cut-off values.

PubMed

Cafarchia, Claudia; Iatta, Roberta; Immediato, Davide; Puttilli, Maria Rita; Otranto, Domenico

2015-09-01

This study aims to determine the minimal inhibitory concentration (MIC) distribution and the epidemiological cut-off values (ECVs) of Malassezia pachydermatis and Malassezia furfur isolates for fluconazole (FLZ), itraconazole (ITZ), posaconazole (POS), and voriconazole (VOR). A total of 62 M. pachydermatis strains from dogs with dermatitis and 78 M. furfur strains from humans with bloodstream infections (BSI) were tested by a modified broth microdilution Clinical and Laboratory Standards Institute (CLSI) method. ITZ and POS displayed lower MICs than VOR and FLZ, regardless of the Malassezia species. The MIC data for azoles of M. pachydermatis were four two-fold dilutions lower than those of M. furfur. Based on the ECVs, about 94% of Malassezia strains might be categorized within susceptible population for all azoles, except for FLZ, and azole cross-resistance was detected in association with FLZ in M. pachydermatis but not in M. furfur.The study proposes, for the first time, tentative azole ECVs for M. pachydermatis and M. furfur for monitoring the emergence of isolates with decreased susceptibilities and shows that the azole MIC distribution varied according to the Malassezia species tested, thus suggesting the usefulness of determining the susceptibility profile for effective treatment of each species. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Action of Monomeric/Gemini Surfactants on Free Cells and Biofilm of Asaia lannensis.

PubMed

Koziróg, Anna; Kręgiel, Dorota; Brycki, Bogumił

2017-11-22

We investigated the biological activity of surfactants based on quaternary ammonium compounds: gemini surfactant hexamethylene-1,6-bis-( N,N -dimethyl- N -dodecylammonium bromide) (C6), synthesized by the reaction of N,N -dimethyl- N- dodecylamine with 1,6-dibromohexane, and its monomeric analogue dodecyltrimethylammonium bromide (DTAB). The experiments were performed with bacteria Asaia lannensis , a common spoilage in the beverage industry. The minimal inhibitory concentration (MIC) values were determined using the tube standard two-fold dilution method. The growth and adhesive properties of bacterial cells were studied in different culture media, and the cell viability was evaluated using plate count method. Both of the surfactants were effective against the bacterial strain, but the MIC of gemini compound was significantly lower. Both C6 and DTAB exhibited anti-adhesive abilities. Treatment with surfactants at or below MIC value decreased the number of bacterial cells that were able to form biofilm, however, the gemini surfactant was more effective. The used surfactants were also found to be able to eradicate mature biofilms. After 4 h of treatment with C6 surfactant at concentration 10 MIC, the number of bacterial cells was reduced by 91.8%. The results of this study suggest that the antibacterial activity of the gemini compound could make it an effective microbiocide against the spoilage bacteria Asaia sp. in both planktonic and biofilm stages.

Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats.

PubMed

Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F

2016-12-01

The aim of the study was to describe the pharmacokinetics and predicted efficacy of meropenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to cats at a single dose of 10 mg/kg. Five adult healthy cats were used. Blood samples were withdrawn at predetermined times over a 12 h period. Meropenem concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed with computer software. Initial estimates were determined using the residual method and refitted by non-linear regression. The time that plasma concentrations were greater than the minimum inhibitory concentration (T >MIC) was estimated by applying bibliographic MIC values and meropenem MIC breakpoint. Maximum plasma concentrations of meropenem were 101.02 µg/ml (C p(0) , IV), 27.21 µg/ml (C max , IM) and 15.57 µg/ml (C max , SC). Bioavailability was 99.69% (IM) and 96.52 % (SC). Elimination half-lives for the IV, IM and SC administration were 1.35, 2.10 and 2.26 h, respectively. Meropenem, when administered to cats at a dose of 10 mg/kg q12h,, is effective against bacteria with MIC values of 6 μg/ml, 7 μg/ml and 10 μg/ml for IV, IM and SC administration, respectively. However, clinical trials are necessary to confirm clinical efficacy of the proposed dosage regimen. © The Author(s) 2015.

Molecular resistance mechanisms of Mycoplasma agalactiae to macrolides and lincomycin.

PubMed

Prats-van der Ham, Miranda; Tatay-Dualde, Juan; de la Fe, Christian; Paterna, Ana; Sánchez, Antonio; Corrales, Juan Carlos; Contreras, Antonio; Gómez-Martín, Ángel

2017-11-01

The extensive use of antimicrobials for disease control has caused a remarkable decrease in antimicrobial susceptibility of different animal mycoplasma species, including Mycoplasma agalactiae (M. agalactiae), the main causative agent of contagious agalactia. However, the molecular mechanisms behind M. agalactiae resistance to macrolides and lincomycin have not yet been elucidated. The aim of the present study was to investigate the association between minimum inhibitory concentration (MIC) values of different antimicrobials and mutations in the 23S rRNA gene and ribosomal proteins L4 and L22, analysing both field isolates (n=50) and in vitro selected resistant mutants of M. agalactiae. The obtained MIC results of the studied field isolates demonstrate an increasing development of tylosin resistance in this bacterium, in comparison to previous studies. Interestingly, predicted amino acid changes in L22 (Ser89Leu and Gln90Lys/His) were the first variations observed when MICs of M. agalactiae started to increase (tylosin MIC ≥0.8μg/ml), whereas mutations at positions 2058 or 2059 of domain V of the 23S rRNA gene appeared from MIC values of 1.6μg/ml. These results were consistent in both field isolates and in vitro selected mutants of M. agalactiae. Thus, although in other mycoplasma species resistance to macrolides and lincosamides had been mainly related to mutations in the 23S rRNA gene, this work demonstrates the role of alterations in ribosomal protein L22 in decreased susceptibility of M. agalactiae. Moreover, these mutations can be used as molecular markers to set an interpretative breakpoint of antimicrobial resistance for M. agalactiae. Copyright © 2017 Elsevier B.V. All rights reserved.

Regression analysis and categorical agreement of fluconazole disk zone diameters and minimum inhibitory concentration by broth microdilution of clinical isolates of Candida.

PubMed

Aggarwal, P; Kashyap, B

2017-06-01

Rampant use of fluconazole in Candida infections has led to predominance of less susceptible non-albicans Candida over Candida albicans. The aim of the study was to determine if zone diameters around fluconazole disk can be used to estimate the minimum inhibitory concentration (MIC) for clinical isolates of Candida species and vice versa. Categorical agreement between the Clinical & Laboratory Standards Institute (CLSI) recommended disk diffusion and CLSI broth microdilution method was sought for. Antifungal susceptibility testing by disk diffusion and Broth microdilution was done as per CLSI document M44-S3 and CLSI document M27-S4 for Candida isolates respectively. Regression analysis correlating zone diameters to MIC value was done. Pearson's correlation coefficient was calculated to determine correlation between disk zone diameters and MICs. Candida albicans (33.3%) was clearly outnumbered by other non-albicans species predominantly Candida tropicalis (42.5%) and Candida glabrata (18.4%). Ten percent of the strains were resistant to fluconazole by disk diffusion and 13% by broth microdilution. MIC range for Candida albicans and Candida tropicalis ranged from≤0.25-64μg/ml while that of Candida glabrata ranged from≤0.25-128μg/ml. Categorical agreement between disk diffusion and broth microdilution was 86.8%. Pearson's coefficient of correlation was -0.5975 indicating moderate negative correlation between the two variables. Zone sizes can be used to estimate the MIC values, although with limited accuracy. There should be a constant effort to upgrade the guidelines in view of new clinical data, and laboratories should make an active effort to incorporate them. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Antibacterial assay-guided isolation of active compounds from Artocarpus heterophyllus heartwoods.

PubMed

Septama, Abdi Wira; Panichayupakaranant, Pharkphoom

2015-01-01

Preparations from Artocarpus heterophyllus Lam. (Moraceae) heartwoods are used in the traditional folk medicine for the treatment of inflammation, malarial fever, and to prevent bacterial and fungal infections. The objective of this study was to isolate pure antibacterial compounds from A. heterophyllus heartwoods. The dried and powdered A. heterophyllus heartwoods were successively extracted with the following solvents: hexane, ethyl acetate, and methanol. Each of the extracts was screened for their antibacterial activities using a disc diffusion method (10 mg/disc). Their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using a broth microdilution method. The extract that showed the strongest antibacterial activities was fractionated to isolate the active compounds by an antibacterial assay-guided isolation process. The ethyl acetate extract exhibited the strongest antibacterial activities against Streptococcus mutans, S. pyogenes, and Bacillus subtilis with MIC values of 78, 39, and 9.8 µg/mL, respectively. Based on an antibacterial assay-guided isolation, four antibacterial compounds: cycloartocarpin (1), artocarpin (2), artocarpanone (3), and cyanomaclurin (4) were purified. Among these isolated compounds, artocarpin exhibited the strongest antibacterial activity against Gram-positive bacteria, including S. mutans, S. pyogenes, B. subtilis, Staphylococcus aureus, and S. epidermidis with MICs of 4.4, 4.4, 17.8, 8.9, and 8.9 µM, respectively, and MBCs of 8.9, 8.9, 17.8, 8.9, and 8.9 µM, respectively, while artocarpanone showed the strongest activity against Escherichia coli, a Gram-negative bacteria with MIC and MBC values of 12.9 and 25.8 µM, respectively. Only artocarpin showed inhibitory activity against Pseudomonas aeruginosa with an MIC of 286.4 µM.

Effects of Intracanal Irrigant MTAD Combined with Nisin at Sub-Minimum Inhibitory Concentration Levels on Enterococcus faecalis Growth and the Expression of Pathogenic Genes

PubMed Central

Ling, Junqi; Mao, Xueli; Ning, Yang; Deng, Dongmei

2014-01-01

Exposure to antibiotics is considered to be the major driver in the selection of antibiotic-resistant bacteria and may induce diverse biological responses in bacteria. MTAD is a common intracanal irrigant, but its bactericidal activity remains to be improved. Previous studies have indicated that the antimicrobial peptide nisin can significantly improve the bactericidal activity of MTAD against Enterococcus faecalis. However, the effects of MTAD and its modification at sub-minimum inhibitory concentration (sub-MIC) levels on Enterococcus faecalis growth and the expression of pathogenic genes still need to be explored. In this study, the results of post-antibiotic effects (PAE) and post-antibiotic sub-MIC effects (PASME) showed that MTADN (nisin in combination with MTAD) had the best post-antibiotic effect. E. faecalis after challenge with MTAD was less sensitive to alkaline solutions compared with MTAN (nisin in place of doxycycline in MTAD) and MTADN. E. faecalis induced with sub-MIC of MTAD generated resistance to the higher concentration, but induction of E. faecalis with MTAN did not cause resistance to higher concentrations. Furthermore, real-time polymerase chain reaction (RT-PCR) showed that the stress caused by sub-MIC exposure to MTAD, MTAN, or MTADN resulted in up- or down-regulation of nine stress genes and four virulence-associated genes in E. faecalis and resulted in different stress states. These findings suggested that nisin improved the post-antibacterial effect of MTAD at sub-MIC levels and has considerable potential for use as a modification of MTAD. PMID:24603760

Pharmacodynamics of moxifloxacin and levofloxacin against Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli: simulation of human plasma concentrations after intravenous dosage in an in vitro kinetic model.

PubMed

Odenholt, Inga; Cars, Otto

2006-11-01

To compare in an in vitro kinetic model the pharmacodynamics of moxifloxacin and levofloxacin with a concentration-time profile simulating the human free non-protein bound concentrations of 400 mg moxifloxacin intravenous (iv) once daily, 500 mg levofloxacin iv once daily and 750 mg levofloxacin iv once daily against strains of Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli with variable susceptibility to fluoroquinolones. The strains used in the study included S. pneumoniae ATCC 6306 (native strain), S. pneumoniae 19397 (double mutation; gyrA and parC), S. pneumoniae 4241 (single mutation; parC), S. aureus ATCC 13709 (native strain), S. aureus MB5 (single mutation; gyrA), E. coli M12 (single mutation; gyrA), E. coli ATCC 25922 (native strain) and K. pneumoniae ATCC 29655 (native strain). The strains were exposed to moxifloxacin and levofloxacin in an in vitro kinetic model simulating the free human serum concentration-time profile of moxifloxacin 400 mg once daily, levofloxacin 500 mg once daily and 750 mg once daily. Repeated samples were taken regularly during 24 h and viable counts were carried out. A correlation was seen between both the area under the serum concentration curve and MIC (AUC/MIC) and the peak concentration/MIC (Cmax/MIC) versus area under the bactericidal killing curve (AUBKC) or Deltalog0-24 cfu/mL. Compiling all data, an AUC/MIC of approximately 100 and a Cmax/MIC of 10 gave a maximal bactericidal effect for both levofloxacin and moxifloxacin. In accordance with the results from others, our study indicated that a lower AUC/MIC was needed for S. pneumoniae in comparison with the Gram-negative bacteria studied. Moxifloxacin yielded higher AUC/MIC and Cmax/MIC against the investigated Gram-positive bacteria in comparison with levofloxacin 500 mg once daily and 750 mg once daily.

Antibacterial activity of BMS-180680, a new catechol-containing monobactam.

PubMed Central

Fung-Tomc, J; Bush, K; Minassian, B; Kolek, B; Flamm, R; Gradelski, E; Bonner, D

1997-01-01

The in vitro activities of a new catechol-containing monobactam, BMS-180680 (SQ 84,100), were compared to those of aztreonam, ceftazidime, imipenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and trimethoprim-sulfamethoxazole. BMS-180680 was often the most active compound against many species of the family Enterobacteriaceae, with MICs at which 90% of the isolates were inhibited (MIC90s) of < or = 0.5 microg/ml for Escherichia coli, Klebsiella spp., Citrobacter diversus, Enterobacter aerogenes, Serratia marcescens, Proteus spp., and Providencia spp. BMS-180680 had moderate activities (MIC90s of 2 to 8 microg/ml) against Citrobacter freundii, Morganella morganii, Shigella spp., and non-E. aerogenes Enterobacter spp. BMS-180680 was the only antibiotic evaluated that was active against >90% of the Pseudomonas aeruginosa (MIC90, 0.25 microg/ml), Burkholderia cepacia, and Stenotrophomonas maltophilia (MIC90s, 1 microg/ml) strains tested. BMS-180680 was inactive against most strains of Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas diminuta, and Burkholderia pickettii. BMS-180680 was moderately active (MIC90s of 4 to 8 microg/ml) against Alcaligenes spp. and Acinetobacter lwoffii and less active (MIC90, 16 microg/ml) against Acinetobacter calcoaceticus-Acinetobacter baumanii complex. BMS-180680 lacked activity against gram-positive bacteria and anaerobic bacteria. Both tonB and cir fiu double mutants of E. coli had greatly decreased susceptibility to BMS-180680. Of the TEM, PSE, and chromosomal-encoded beta-lactamases tested, only the K1 enzyme hydrolyzed BMS-180680 to any measurable extent. Like aztreonam, BMS-180680 bound preferentially to penicillin-binding protein 3. The MICs of BMS-180680 were not influenced by the presence of hematin or 5% sheep blood in the test medium or with incubation in an atmosphere containing 5% CO2. BMS-180680 MICs obtained under strict anaerobic conditions were significantly higher than those obtained in ambient air. PMID:9145861

Sources of diversity of carbapenem resistance levels in Klebsiella pneumoniae carrying blaVIM-1.

PubMed

Loli, A; Tzouvelekis, L S; Tzelepi, E; Carattoli, A; Vatopoulos, A C; Tassios, P T; Miriagou, V

2006-09-01

To elucidate the mechanisms responsible for the diversity of beta-lactam resistance phenotypes among isolates of a VIM-1-producing Klebsiella pneumoniae (VPKP) strain that is endemic in Greek hospitals. Five VPKP clinical isolates were studied. MICs of beta-lactams were determined by agar dilution. PFGE of XbaI-digested genomic DNA was used for typing. Profiles of outer membrane proteins (OMPs) were determined by SDS-PAGE. Selected isolates were transformed with a plasmid encoding the Omp36K porin. beta-Lactamase activities were analysed by IEF and imipenem hydrolysis was assessed by spectrophotometry. VIM-1-encoding, self-transmissible plasmids were characterized by replicon typing, RFLP and hybridization with bla(VIM)- and IS26-specific probes. Characterization of integrons was performed by PCR, cloning and sequencing. Isolates exhibited highly similar PFGE patterns. Imipenem MICs were 2, 4, 16, 32 and 64 mg/L. The isolate with the highest imipenem MIC (Vipm-64) lacked a 36 kDa OMP. Expression of a cloned OmpK36 in this isolate reduced the imipenem MIC to susceptibility levels. Imipenem-hydrolysing activity was significantly higher in Vipm-16 as compared with the other isolates that expressed similar amounts of VIM-1. All isolates transferred beta-lactam resistance to Escherichia coli through conjugative, IncN plasmids that exhibited differences in the RFLP and hybridization patterns with bla(VIM)- and IS26-specific probes. The Vipm-16 plasmid, mediating the higher imipenem MICs among transconjugants, carried two copies of bla(VIM-1). Cloning and sequencing showed In-e541-like integrons truncated at the 5'CS by insertion of IS26 elements at two different positions. A VIM-1-producing strain of K. pneumoniae has evolved through OMP alterations and rearrangements in the bla(VIM-1)-carrying plasmid probably mediated by IS26, generating isolates with imipenem MICs ranging from susceptibility to resistance.

Pharmacodynamic Evaluation of the Intracellular Activity of Antibiotics towards Pseudomonas aeruginosa PAO1 in a Model of THP-1 Human Monocytes

PubMed Central

Buyck, Julien M.; Tulkens, Paul M.

2013-01-01

Pseudomonas aeruginosa invades epithelial and phagocytic cells, which may play an important role in the persistence of infection. We have developed a 24-h model of THP-1 monocyte infection with P. aeruginosa PAO1 in which bacteria are seen multiplying in vacuoles by electron microscopy. The model has been used to quantitatively assess antibiotic activity against intracellular and extracellular bacteria by using a pharmacodynamic approach (concentration-dependent experiments over a wide range of extracellular concentrations to calculate bacteriostatic concentrations [Cs] and maximal relative efficacies [Emax]; Hill-Langmuir equation). Using 16 antipseudomonal antibiotics (three aminoglycosides, nine β-lactams, three fluoroquinolones, and colistin), dose-response curves were found to be undistinguishable for antibiotics of the same pharmacological class if data were expressed as a function of the corresponding MICs. Extracellularly, all of the antibiotics reached a bacteriostatic effect at their MIC, and their Emax exceeded the limit of detection (−4.5 log10 CFU compared to the initial inoculum). Intracellularly, Cs values remained unchanged for β-lactams, fluoroquinolones, and colistin but were approximately 10 times higher for aminoglycosides, whereas Emax values were markedly reduced (less negative), reaching −3 log10 CFU for fluoroquinolones and only −1 to −1.5 log10 CFU for all other antibiotics. The decrease in intracellular aminoglycoside potency (higher Cs) can be ascribed to the acid pH to which bacteria are exposed in vacuoles. The decrease in the Emax may reflect a reversible alteration of bacterial responsiveness to antibiotics in the intracellular milieu. The model may prove useful for comparison of antipseudomonal antibiotics to reduce the risk of persistence or relapse of pseudomonal infections. PMID:23478951

Structural requirements for the antifungal activities of natural drimane sesquiterpenes and analogues, supported by conformational and electronic studies.

PubMed

Derita, Marcos; Montenegro, Iván; Garibotto, Francisco; Enriz, Ricardo D; Fritis, Mauricio Cuellar; Zacchino, Susana A

2013-02-05

Seventeen drimanes including polygodial (1), isopolygodial (2), drimenol (3) and confertifolin (4) obtained from natural sources and the semi-synthetic derivatives 5-17 obtained from 1-3, were evaluated in vitro for antifungal properties against a unique panel of fungi with standardized procedures by using two end-points, MIC(100) and MIC(50). A SAR analysis of the whole series, supported by conformational and electronic studies, allowed us to show that the Δ7,8 -double bond would be one of the key structural features related to the antifungal activity. The MEPs obtained for active compounds exhibit a clear negative minimum value (deep red zone) in the vicinity of the Δ7,8 -double bond, which is not present in the inactive ones. Apart of this negative zone, a positive region (deep blue) appears in 1, which is not observed either in its epimer 2 nor in the rest of the active compounds. The LogP of active compounds varies between 2.33 and 3.84, but differences in MICs are not correlated with concomitant variations in LogP values.

Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.

PubMed

Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

2018-04-01

The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CL CR ). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval ( fT MIC ) of 65% for an MIC of 8 mg/liter in patients with a CL CR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CL CR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CL CR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CL CR values (≤30 ml/min). Copyright © 2018 American Society for Microbiology.

Activity of a Long-Acting Echinocandin (CD101) and Seven Comparator Antifungal Agents Tested against a Global Collection of Contemporary Invasive Fungal Isolates in the SENTRY 2014 Antifungal Surveillance Program.

PubMed

Pfaller, Michael A; Messer, Shawn A; Rhomberg, Paul R; Castanheira, Mariana

2017-03-01

The activity of CD101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the Clinical and Laboratory Standards Institute (CLSI) method. All Candida albicans ( n = 251), Candida tropicalis ( n = 51), Candida krusei ( n = 16), and Candida dubliniensis ( n = 11) isolates were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. Five C. glabrata isolates ( n = 100) displayed CD101 MIC values of 1 to 4 μg/ml, had elevated MICs of caspofungin (2 to >8 μg/ml), anidulafungin (2 to 4 μg/ml), and micafungin (2 to 4 μg/ml), and carried mutations on fks1 and fks2 Candida parapsilosis ( n = 92) and Candida orthopsilosis ( n = 10) displayed higher CD101 MIC values (ranges, 0.5 to 4 μg/ml and 0.12 to 2 μg/ml, respectively), and similar results were observed for the other echinocandins tested. Fluconazole resistance was noted among 11.0% of Candida glabrata isolates, 4.3% of C. parapsilosis isolates, and 2.0% of C. albicans and C. tropicalis isolates. The activity of CD101 against Aspergillus fumigatus ( n = 56) was similar to that of micafungin and 2-fold greater than that of caspofungin but less than that of anidulafungin. These isolates had wild-type susceptibility to itraconazole, voriconazole, and posaconazole. The echinocandins had limited activity against Cryptococcus neoformans ( n = 19). CD101 was as active as the other echinocandins against common fungal organisms recovered from patients with invasive fungal infections. The long half-life profile is very desirable for the prevention and treatment of serious fungal infections, especially in patients who can then be discharged from the hospital to complete antifungal therapy on an outpatient basis. Copyright © 2017 Pfaller et al.

Change of point mutations in Helicobacter pylori rRNA associated with clarithromycin resistance in Italy.

PubMed

De Francesco, Vincenzo; Zullo, Angelo; Giorgio, Floriana; Saracino, Ilaria; Zaccaro, Cristina; Hassan, Cesare; Ierardi, Enzo; Di Leo, Alfredo; Fiorini, Giulia; Castelli, Valentina; Lo Re, Giovanna; Vaira, Dino

2014-03-01

Primary clarithromycin resistance is the main factor affecting the efficacy of Helicobacter pylori therapy. This study aimed: (i) to assess the concordance between phenotypic (culture) and genotypic (real-time PCR) tests in resistant strains; (ii) to search, in the case of disagreement between the methods, for point mutations other than those reported as the most frequent in Europe; and (iii) to compare the MICs associated with the single point mutations. In order to perform real-time PCR, we retrieved biopsies from patients in whom H. pylori infection was successful diagnosed by bacterial culture and clarithromycin resistance was assessed using the Etest. Only patients who had never been previously treated, and with H. pylori strains that were either resistant exclusively to clarithromycin or without any resistance, were included. Biopsies from 82 infected patients were analysed, including 42 strains that were clarithromycin resistant and 40 that were clarithromycin susceptible on culture. On genotypic analysis, at least one of the three most frequently reported point mutations (A2142C, A2142G and A2143G) was detected in only 23 cases (54.8%), with a concordance between the two methods of 0.67. Novel point mutations (A2115G, G2141A and A2144T) were detected in a further 14 out of 19 discordant cases, increasing the resistance detection rate of PCR to 88% (P<0.001; odds ratio 6.1, 95% confidence interval 2-18.6) and the concordance to 0.81. No significant differences in MIC values among different point mutations were observed. This study suggests that: (i) the prevalence of the usually reported point mutations may be decreasing, with a concomitant emergence of new mutations; (ii) PCR-based methods should search for at least six point mutations to achieve good accuracy in detecting clarithromycin resistance; and (iii) none of the tested point mutations is associated with significantly higher MIC values than the others.

Comparison of gatifloxacin and levofloxacin administered at various dosing regimens to hospitalised patients with community-acquired pneumonia: pharmacodynamic target attainment study using North American surveillance data for Streptococcus pneumoniae.

PubMed

Noreddin, Ayman M; Hoban, Daryl J; Zhanel, George G

2005-08-01

This work aimed at determining the target attainment potential of gatifloxacin and levofloxacin in specific age-related patient populations such as elderly (> or =65 years) versus younger (<65 years) hospitalised patients with community-acquired pneumonia (CAP). Previously described population pharmacokinetic models of gatifloxacin and levofloxacin administration in patients with serious CAP were utilised to simulate gatifloxacin and levofloxacin pharmacokinetics. Pharmacokinetic simulations and susceptibility data for Streptococcus pneumoniae from the ongoing national surveillance study, Canadian Respiratory Organism Susceptibility Study (CROSS), were then used to produce pharmacodynamic indices of free-drug area under the curve over 24h relative to the minimum inhibitory concentration (free-drug AUC(0-24)/MIC(all)). Monte Carlo simulations were then used to analyse target attainment both of gatifloxacin and levofloxacin to achieve free-drug AUC(0-24)/MIC(all)> or =30 against S. pneumoniae in patients with CAP. Dosing regimens for gatifloxacin were 400 mg once daily (qd) administered to younger patients (<65 years) and gatifloxacin 200 mg qd to elderly patients (> or =65 years). Dosing regimens for levofloxacin were simulated as 500 mg, 750 mg and 1000 mg qd administered to elderly patients as well as younger patients. Monte Carlo simulations using gatifloxacin 400mg against S. pneumoniae yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 96.6% for all patients, 92.3% for younger patients and 97.7% for elderly patients. When administered to elderly patients, a reduced dose of gatifloxacin 200mg qd could achieve a target attainment potential of 91.4%. Monte Carlo simulation using levofloxacin 500 mg qd yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 92.3% for all patients, 95.7% for elderly patients compared with 72.7% for younger patients. Using levofloxacin 750 mg and 1000 mg qd had probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 of 97.0% and 98.3%, 98.1% and 99.2%, and 90.1% and 95.2% for all patients, elderly patients and younger patients, respectively. The probability of achieving free-drug AUC(0-24)/MIC(all) of 100 was low both with gatifloxacin and levofloxacin, except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg qd (78.5%). We conclude that gatifloxacin and levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patients. Higher gatifloxacin/levofloxacin AUC and longer half-life (t(1/2)) values in elderly patients with CAP compared with younger patients provide better pharmacodynamic parameters (free-drug AUC(0-24)/MIC) leading to a higher probability of pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae. Gatifloxacin 400mg qd results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae both in young and elderly CAP patients. However, gatifloxacin administered at a lowered dose of 200 mg qd in elderly patients could still be successful in producing a favourable antibacterial effect. Levofloxacin administered at a dose of 750 mg qd results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae in all patients with CAP.

Postoperative corneal shape changes: microincision versus small-incision coaxial cataract surgery.

PubMed

Hayashi, Ken; Yoshida, Motoaki; Hayashi, Hideyuki

2009-02-01

To compare changes in corneal topography and in regular and irregular astigmatism after coaxial clear corneal microincision cataract surgery (MICS) and after coaxial small-incision cataract surgery (SICS). Hayashi Eye Hospital, Fukuoka, Japan. Induced corneal astigmatism was determined using vector analysis. The averaged corneal shape changes and degree of irregular astigmatism were examined using videokeratography preoperatively as well as 2 days and 1, 2, 4, and 8 weeks postoperatively. One hundred twenty eyes of 60 patients scheduled for phacoemulsification were evaluated. Sixty eyes had MICS (2.00 mm), and the 60 contralateral eyes had SICS (2.65 mm). The mean induced corneal astigmatism was significantly less in the MICS group than in the SICS group (P

Water Disinfection Byproducts Induce Antibiotic Resistance-Role of Environmental Pollutants in Resistance Phenomena.

PubMed

Li, Dan; Zeng, Siyu; He, Miao; Gu, April Z

2016-03-15

The spread of antibiotic resistance represents a global threat to public health, and has been traditionally attributed to extensive antibiotic uses in clinical and agricultural applications. As a result, researchers have mostly focused on clinically relevant high-level resistance enriched by antibiotics above the minimal inhibitory concentrations (MICs). Here, we report that two common water disinfection byproducts (chlorite and iodoacetic acid) had antibiotic-like effects that led to the evolution of resistant E. coli strains under both high (near MICs) and low (sub-MIC) exposure concentrations. The subinhibitory concentrations of DBPs selected strains with resistance higher than those evolved under above-MIC exposure concentrations. In addition, whole-genome analysis revealed distinct mutations in small sets of genes known to be involved in multiple drug and drug-specific resistance, as well as in genes not yet identified to play role in antibiotic resistance. The number and identities of genetic mutations were distinct for either the high versus low sub-MIC concentrations exposure scenarios. This study provides evidence and mechanistic insight into the sub-MIC selection of antibiotic resistance by antibiotic-like environmental pollutants such as disinfection byproducts in water, which may be important contributors to the spread of global antibiotic resistance. The results from this study open an intriguing and profound question on the roles of large amount and various environmental contaminants play in selecting and spreading the antibiotics resistance in the environment.

Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

PubMed

Cunico, Miriam M; Trebien, Herbert A; Galetti, Fábio C; Miguel, Obdulio G; Miguel, Marilis D; Auer, Celso G; Silva, Célio L; de Souza, Ana Olívia

2015-01-01

Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively.

Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Essential Oils of Selected Aromatic Plants from Tajikistan.

PubMed

Sharopov, Farukh; Braun, Markus Santhosh; Gulmurodov, Isomiddin; Khalifaev, Davlat; Isupov, Salomiddin; Wink, Michael

2015-11-02

Antimicrobial, antioxidant, and anti-inflammatory activities of the essential oils of 18 plant species from Tajikistan (Central Asia) were investigated. The essential oil of Origanum tyttanthum showed a strong antibacterial activity with both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 312.5 µg/mL for E. coli , 625 µg/mL (MIC) and 1250 µg/mL (MBC) for MRSA (methicillin-resistant Staphylococcus aureus), respectively. The essential oil of Galagania fragrantissima was highly active against MRSA at concentrations as low as 39.1 µg/mL and 78.2 µg/mL for MIC and MBC, respectively. Origanum tyttanthum essential oil showed the highest antioxidant activity with IC 50 values of 0.12 mg/mL for ABTS (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)) and 0.28 mg/mL for DPPH (2,2-diphenyl-1-picrylhydrazyl) . Galagania fragrantissima and Origanum tyttanthum essential oils showed the highest anti-inflammatory activity; IC 50 values of 5-lipoxygenase (5-LOX) inhibition were 7.34 and 14.78 µg/mL, respectively. In conclusion, essential oils of Origanum tyttanthum and Galagania fragrantissima exhibit substantial antimicrobial, antioxidant, and anti-inflammatory activities. They are interesting candidates in phytotherapy.

Anti-fungal and Anti-Mycobacterial activity of plants of Nuevo Leon, Mexico.

PubMed

Garza, Blanca Alicia Alanis; Arroyo, Joel López; González, Gloria González; González, Elvira Garza; González, Elvira Garza; de Torres, Noemí Waksman; Aranda, Ricardo Salazar

2017-01-01

Severe fungal infections, particularly those caused by Candida spp, have increased in recent decades and are associated with an extremely high rate of morbidity and mortality. Since plants are an important source of potentially bioactive compounds, in this work the antifungal activity of the methanol extracts of 10 plants (Acacia rigidula, Buddleja cordata, Cephalanthus occidentalis, Juglans nigra, Parkinsonia aculeata, Parthenium hysterophorus, Quercus canbyi, Ricinus communis, Salvia coccinea and Teucrium bicolor) were evaluated. The activity was evaluated according to the micro dilution assay described in CLSI M27-A protocol using some clinical isolates of different species of Candida (C. albicans, C. parapsilosis, C. tropicalis, C. krusei and C. glabrata). All extracts showed MIC values < 31.25μg/mL against at least one of the strains used, which is very interesting because it was crude extracts. Acacia rigidula (0.93-3.75μg/mL) and Quercus canbyi (0.93-7.5μg/mL) had antifungal activity against 7 strains with MIC values <8μg/mL in all cases. Furthermore excerpts activity against Mycobacterium tuberculosis (strain H37rv) was evaluated. Only Salvia coccinea and Teucrium bicolor showed MIC values125μg/mL by the method of MABA.

Postantibiotic effect of various antibiotics on Legionella pneumophila strains isolated from water systems.

PubMed

Birteksöz-Tan, Ayşe Seher; Zeybek, Zuhal

2012-11-01

The postantibiotic effects (PAE) of azithromycin, clarithromycin, ciprofloxacin, and levofloxacin were investigated against Legionella pneumophila (L. pneumophila) strains isolated from several hot water systems of different buildings in Istanbul. Each strain in logarithmic phase of growth was exposed to concentrations of antibiotics equal to minimum inhibitory concentration (MIC) and 4× MIC for 1 h. Recovery periods of test cultures were evaluated after centrifugation using the viable counting method. The mean values of PAEs for the strains of L. pneumophila, azithromycin at a concentration equal to and 4 times of MIC values were found 1.75 ± 0.28 h and 4.06 ± 0.44 h, for clarithromycin 2.98 ± 0.70 h and 4.18 ± 0.95 h, for ciprofloxacin 2.97 ± 0.63 h and 4.70 ± 0.63 h, for levofloxacin 2.05 ± 0.33 h and 3.78 ± 0.46 h, respectively. All of the antibiotics showed increased PAE values in a concentration-dependent manner. The findings of our study may play useful role in selecting the appropriate timing of doses during therapy with antimicrobials to treat patients infected with L. pneumophila.

In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.

PubMed

Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

2004-05-01

We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.

Extracellular DNA Impedes the Transport of Vancomycin in Staphylococcus epidermidis Biofilms Preexposed to Subinhibitory Concentrations of Vancomycin

PubMed Central

Tseng, Boo Shan; Howlin, Robert P.; Deacon, Jill; Wharton, Julian A.; Thurner, Philipp J.; Gilmore, Brendan F.; Parsek, Matthew R.; Stoodley, Paul

2014-01-01

Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treated S. epidermidis biofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellular d-Ala-d-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections. PMID:25267673

Novel designed VmCT1 analogs with increased antimicrobial activity.

PubMed

Pedron, Cibele Nicolaski; Torres, Marcelo Der Torossian; Lima, Julia Aparecida da Silva; Silva, Pedro Ismael; Silva, Fernanda Dias; Oliveira, Vani Xavier

2017-01-27

Antimicrobial peptides are biologically active molecules produced by a wide range of organisms as an essential component of the innate immune response. They have recently attracted great interest, since they have antimicrobial activity against a broad spectrum of microorganisms. VmCT1 is a cationic peptide from the venom of Vaejovis mexicanus smithi scorpions, which presents antibacterial activity and tends to helical structures. Its analogs were synthesized, characterized and the conformational studies were performed by circular dichroism. The peptides were designed to verify if the single and double substitutions proposed at the hydrophilic and hydrophobic portions of the amphipathic structure would alter antimicrobial activity against Gram-negative and Gram-positive bacteria, yeast and filamentous fungus, besides the hemolytic activity in human erythrocytes. Total charge of the peptides were modified from +2 to +3 by the introduction of a Lysine residue in the hydrophilic face of the amphiphilic helical structure leading to enhanced antimicrobial activity. [K] 11 -VmCT1-NH 2 presented the lower MIC value against the microorganisms (from 0.39 to 6.25 μmol L -1 ), however it showed higher hemolytic activity. The other Lysine-substituted analogs presented also lower MIC values ranging from 0.39 to 25 μmol L -1 for the microorganisms assessed. The circular dichroism spectra analyses suggest that the Lysine-substituted analogs tend to adopt helical structures in trifluoroethanol solution and vesicles (f H : 0.43-1), however they were coiled in water. Alanine substitution by a Glutamic acid residue in the hydrophilic face promotes the increase of polar angle in [E] 4 -VmCT1-NH 2 analog, which was important to led lower hemolytic activity (MHC value = 25 μmol L -1 ). [W] 9 -VmCT1-NH 2 and [E] 4 [W] 9 -VmCT1-NH 2 were designed to favors hydrophobic interactions by the introduction of Tryptophan residue. [W] 9 -VmCT1-NH 2 presented MIC values lower or similar than the model molecule in the most of microorganisms tested. These results provided information about the structure-activity relationship and showed the influence of physicochemical parameters on antimicrobial and hemolytic activity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Development of a Highly Biocompatible Antituberculosis Nanodelivery Formulation Based on Para-Aminosalicylic Acid—Zinc Layered Hydroxide Nanocomposites

PubMed Central

Arulselvan, Palanisamy; El Zowalaty, Mohamed Ezzat; Fakurazi, Sharida; Webster, Thomas J.; Geilich, Benjamin; Hussein, Mohd Zobir

2014-01-01

Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 μg/mL compared to the free drug PAS with a MIC of 5.0 μg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies. PMID:25050392

Comparison of MICs of Fluconazole and Flucytosine When Dissolved in Dimethyl Sulfoxide or Water

PubMed Central

Fothergill, Annette W.; Sanders, Carmita

2013-01-01

A total of 145 clinical strains of Candida species were tested by the Clinical and Laboratory Standards Institute M27-A3 methodology to determine if replacing water with dimethyl sulfoxide as the solvent for fluconazole and flucytosine impacted the in vitro potency. No significant differences in MIC values were observed with either antifungal between the two solvents against any Candida species, and the essential agreement for each agent between the two solvents was greater than 99%. PMID:23576540

[Sinusal penetration of amoxicillin-clavulanic acid. Formulation 1 g./125 mg., twice daily versus formulation 500 mg./125 mg., three times daily].

PubMed

Jehl, F; Klossek, J M; Peynegre, R; Serrano, E; Castillo, L; Bobin, S; Desprez, D; Renault, C; Neel, V; Rouffiac, E; Borie, C

2002-10-19

In order to meet the evolution of pneumococcus resistance to beta-lactam antibiotics, a new formulation of amoxicillin (AMX) and clavulanic acid (CA), with twice as much AMX (1 g/125 mg vs. 500 mg/125 mg) was developed for the treatment of acute pneumonia in patients at risk. This formulation can also be used in the treatment of acute maxillary sinusitis using a 1 g/125 mg regimen twice-daily. Compare the sinusal penetration of AMX and CA (1 g/125 mg twice-daily vs. 500 mg/125 mg three times a day) when administered at both regimens to demonstrate equivalent pharmacokinetic and pharmacodynamic behaviour of the former when compared to the latter. Concentrations of AMX and CA were measured in the anterior ethmoid, maxillary, posterior ethmoid sinus and in the middle nasa concha in 62 patients undergoing surgery for nasosinusal polyps. Patients randomised in two groups corresponding to 2 oral regimens, received either 1 g/125 mg twice a day or 500 mg/125 mg three times a day for 4 days. The last dose in both groups was administered 1 h 30, 3, 5 or 8 hrs prior to surgery. Serum samples were taken simultaneously to tissue samples. AMX and CA were measured by high performance liquid chromatography. Exogenous and above all endogenous blood contamination were taken into account with the hematocrit as well as blood and tissue haemoglobin concentrations. Comparisons of tissue concentrations were made for each sampling time, according to values obtained for a specific tissue with both doses on one hand, and on the other to values obtained with a specific dose in different tissues. The calculated pharmacodynamic parameters, which are considered to be predictive for bacteriological and clinical efficacy, result directly from tissue concentrations of AMX. tissue inhibitory quotients (IQtissue = Tissue concentration/MIC). time above MICs for serum and tissue concentrations (T > MIC). As regards AMX, whatever the dose, at 1 h 30 and at 3 hrs, tissue concentrations did not differ significantly whatever the tissue studied (from 1.1 to 2.5 micrograms/g). Conversely, at 5 and 8 hrs, they were greater than after the 1 g/125 mg regimen given twice-daily (0.06-0.7 vs. 0.7-1.8 micrograms/g). If we consider a given dose, the comparison between the various tissues showed identical concentrations in the four tissues studied at each sampling time, except in two cases with the dose of 500 mg/125 mg 3 times a day. T > MIC for serum and tissue showed higher values than those required for AMX/pneumococcus association (40-50%) with, nevertheless, greater tissue values for the 1 g/125 mg dose given twice-daily when MIC was of 1 microgram/ml (40-52% vs. 50-66%). The maximum tissue inhibitory quotients were also greater with the twice-daily 1 g/125 mg dose, when calculated with MIC 50 or 90 of S. Pneumoniae, H. influenzae, M. catarrhalis or S. pyogenes. As for CA, concentrations were equivalent for both doses at each sampling time and greater than those required in vitro during respectively 4 and 5 hours for beta-lactamases H. influenzae and M. catarrhalis. A least an equivalence between both dose regimens was observed, with occasionally a superiority of the twice-daily 1 g/125 mg dose, in terms of pharmacokinetics, tissue penetration and pharmacodynamics for both AMX and CA. This new regimen therefore appears more appropriate for the treatment of acute maxillary sinusitis in adults.

Antimycobacterial potency and cytotoxicity study of three medicinal plants.

PubMed

Tsouh Fokou, Patrick Valere; Appiah-Opong, Regina; Yeboah-Manu, Dorothy; Kissi-Twum, Abena Adomah; Yamthe, Lauve Rachel Tchokouaha; Mokale Kognou, Aristide Laurel; Addo, Phyllis; Boyom, Fabrice Fekam; Nyarko, Alexander Kwadwo

2016-12-01

Mycobacterial infections including tuberculosis, leprosy, and buruli ulcer are among the most prevalent, debilitating, and deadly tropical diseases, especially in Sub-Saharan Africa. The development of drug resistance to the currently available drugs and the poor compliance emphasize the need for new chemotherapeutic agents. This study was designed to evaluate the in vitro activity of Cleistopholis patens, Annona reticulata, and Greenwayodendron suaveolens against Mycobacterium smegmatis. The safety on normal liver cells was also assessed. The crude extracts, fractions, and subfractions were tested against M. smegmatis and for cell cytotoxicity on WRL-68, normal human hepatocyte using microdilution resazurin-based assays. The phytochemical screening was performed using standard methods. Most of the extracts, fractions, and subfractions inhibited the growth of M. smegmatis with minimum inhibitory concentration (MIC) values ranging from 6.25μg/mL to 125μg/mL. The subfractions P12 and P29 from G. suaveolens twig were more potent with MIC values of 6.25μg/mL and 25μg/mL, respectively. Fruit crude extract and root CH 2 Cl 2 fraction from A. reticulata also showed activity with MIC values of 50μg/mL and 25μg/mL, respectively. Crude extracts from the twig and stem bark of C. patens displayed inhibition at MIC values of 125μg/mL and 100μg/mL, respectively. Majority of active extracts showed no cell cytotoxicity, except the extract from C. patens with IC 50 ranging from 41.40μg/mL to 93.78μg/mL. The chemical investigation of the promising extracts revealed the presence of phenols, alkaloids, glycosides, triterpenes, and acetogenins. The results achieved from this preliminary antimycobacterial drug discovery study supported the traditional claims of C. patens, A. reticulata, and G. suaveolens in the treatment of mycobacterial infections. Meanwhile, further fractionation is required to characterize the active ingredients. Copyright © 2016.

Using ROC Curves to Choose Minimally Important Change Thresholds when Sensitivity and Specificity Are Valued Equally: The Forgotten Lesson of Pythagoras. Theoretical Considerations and an Example Application of Change in Health Status

PubMed Central

Froud, Robert; Abel, Gary

2014-01-01

Background Receiver Operator Characteristic (ROC) curves are being used to identify Minimally Important Change (MIC) thresholds on scales that measure a change in health status. In quasi-continuous patient reported outcome measures, such as those that measure changes in chronic diseases with variable clinical trajectories, sensitivity and specificity are often valued equally. Notwithstanding methodologists agreeing that these should be valued equally, different approaches have been taken to estimating MIC thresholds using ROC curves. Aims and objectives We aimed to compare the different approaches used with a new approach, exploring the extent to which the methods choose different thresholds, and considering the effect of differences on conclusions in responder analyses. Methods Using graphical methods, hypothetical data, and data from a large randomised controlled trial of manual therapy for low back pain, we compared two existing approaches with a new approach that is based on the addition of the sums of squares of 1-sensitivity and 1-specificity. Results There can be divergence in the thresholds chosen by different estimators. The cut-point selected by different estimators is dependent on the relationship between the cut-points in ROC space and the different contours described by the estimators. In particular, asymmetry and the number of possible cut-points affects threshold selection. Conclusion Choice of MIC estimator is important. Different methods for choosing cut-points can lead to materially different MIC thresholds and thus affect results of responder analyses and trial conclusions. An estimator based on the smallest sum of squares of 1-sensitivity and 1-specificity is preferable when sensitivity and specificity are valued equally. Unlike other methods currently in use, the cut-point chosen by the sum of squares method always and efficiently chooses the cut-point closest to the top-left corner of ROC space, regardless of the shape of the ROC curve. PMID:25474472

Process Analysis of Variables for Standardization of Antifungal Susceptibility Testing of Nonfermentative Yeasts ▿

PubMed Central

Zaragoza, Oscar; Mesa-Arango, Ana C.; Gómez-López, Alicia; Bernal-Martínez, Leticia; Rodríguez-Tudela, Juan Luis; Cuenca-Estrella, Manuel

2011-01-01

Nonfermentative yeasts, such as Cryptococcus spp., have emerged as fungal pathogens during the last few years. However, standard methods to measure their antifungal susceptibility (antifungal susceptibility testing [AST]) are not completely reliable due to the impaired growth of these yeasts in standard media. In this work, we have compared the growth kinetics and the antifungal susceptibilities of representative species of nonfermentative yeasts such as Cryptococcus neoformans, Cryptococcus gattii, Cryptococcus albidus, Rhodotorula spp., Yarrowia lipolytica, Geotrichum spp., and Trichosporon spp. The effect of the growth medium (RPMI medium versus yeast nitrogen base [YNB]), glucose concentration (0.2% versus 2%), nitrogen source (ammonium sulfate), temperature (30°C versus 35°C), shaking, and inoculum size (103, 104, and 105 cells) were analyzed. The growth rate, lag phase, and maximum optical density were obtained from each growth experiment, and after multivariate analysis, YNB-based media demonstrated a significant improvement in the growth of yeasts. Shaking, an inoculum size of 105 CFU/ml, and incubation at 30°C also improved the growth kinetics of organisms. Supplementation with ammonium sulfate and with 2% glucose did not have any effect on growth. We also tested the antifungal susceptibilities of all the isolates by the reference methods of the CLSI and EUCAST, the EUCAST method with shaking, YNB under static conditions, and YNB with shaking. MIC values obtained under different conditions showed high percentages of agreement and significant correlation coefficient values between them. MIC value determinations according to CLSI and EUCAST standards were rather complicated, since more than half of isolates tested showed a limited growth index, hampering endpoint determinations. We conclude that AST conditions including YNB as an assay medium, agitation of the plates, reading after 48 h of incubation, an inoculum size of 105 CFU/ml, and incubation at 30°C made MIC determinations easier without an overestimation of MIC values. PMID:21245438

Characterisation of penicillin and tetracycline resistance in Staphylococcus aureus isolated from bovine milk samples in Minas Gerais, Brazil.

PubMed

Martini, Caroline L; Lange, Carla C; Brito, Maria Avp; Ribeiro, João B; Mendonça, Letícia C; Vaz, Eliana K

2017-05-01

This Regional Research Communication describes the characterisation of ampicillin, penicillin and tetracycline resistance in Staphylococcus aureus isolated from bovine subclinical mastitis in Minas Gerais State, Brazil. Ninety S. aureus isolates from bovine mastitis exhibiting phenotypic resistance to ampicillin, penicillin and/or tetracycline were selected for this study. The minimum inhibitory concentration (MIC) of each antibiotic was determined using the E-Test® and the production of beta-lactamase was determined by cefinase disks. The resistance genes blaZ, tet(K), tet(L), tet(M), and tet(O) were investigated by PCR in all of the isolates. The MIC results classified 77, 83 and 71% of the isolates as resistant to ampicillin, penicillin and tetracycline, respectively. The MIC50 and MIC90 were, respectively, 1 and 2 µg/ml for ampicillin, 0·5 and 1 µg/ml for penicillin and 32 and 64 µg/ml for tetracycline. Eighty-six per cent of beta-lactamase producing isolates were detected. Of the 90 isolates investigated, 97% amplified blaZ, 84% amplified tet(K), 9% amplified tet(L), 2% amplified tet(M) and 1% amplified tet(O). Seventy-nine isolates (88%) showed blaZ together with at least one tet gene. S. aureus isolates showed high MIC50 and MIC90 values for the three antimicrobials. The blaZ and tet(K) genes were widespread in the herds studied, and most of the isolates harboured blaZ and tet(K) concomitantly.

Pilot Study of Antimicrobial Resistance in Northern Bobwhites (Colinus virginianus).

PubMed

Zhang, Michael; Shen, Zhenyu; Rollins, Dale; Fales, William; Zhang, Shuping

2017-09-01

Antimicrobial resistance (AMR) is an important issue for both wildlife conservation and public health. The purpose of this study was to screen for AMR in fecal bacteria isolated from northern bobwhite (Colinus virginianus), a species that is an ecologically and economically important natural resource in the southern United States. The antimicrobial susceptibility profiles of 45 Escherichia coli isolates, 20 Enterococcus faecalis isolates, and 10 Enterococcus faecium isolates were determined using the Sensititer TM microbroth dilution minimum inhibitory concentration (MIC) plate, AVIAN1F. Overall, E. coli isolates had high MIC values for the following classes of antimicrobials: aminocoumarins, beta-lactams, lincosamides, macrolides, florfenicol, and sulfonamides. Enterococcus faecalis and E. faecium isolates had high MICs for aminocyclitols, aminoglycosides, beta-lactams, lincosamides, and sulfonamides. Enterococcus faecalis isolates also showed high MICs for aminocoumarins, while E. faecium isolates had high MICs for trimethoprim/sulfamethoxazole and tetracycline. Based on available veterinary interpretive criteria, 15% and 33% of E. coli isolates were resistant to sulphathiazole and sulphadimethoxine, respectively. Intermediate susceptibility to florfenicol was seen with 17.8% of E. coli isolates. Twenty percent of E. faecalis and 80% of E. faecium isolates were resistant to high-concentration streptomycin. One third of E. faecalis and 70% of E. faecium isolates were intermediately susceptible to erythromycin. Ten percent of E. faecium isolates were resistant to tetracycline and oxytetracycline. A comparison of available MIC suggests that AMR in wild bobwhite is less severe than in domestic poultry. Further investigation is needed to determine the source of AMR in wild bobwhite.

Determination of the antimicrobial susceptibilities of Canadian isolates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Canadian Antimicrobial Study Group.

PubMed

Blondeau, J M; Suter, M; Borsos, S

1999-03-01

The susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several antimicrobial agents were tested by two different methods. Beta-lactamase was produced by 68/211 (32.2%) of H. influenzae isolates and 64/75 (85.3%) of M. catarrhalis isolates. For S. pneumoniae, 19/156 (12.2%) isolates were resistant to penicillin (MIC > or = 0.12 mg/L) and two isolates had MICs of 1.5 mg/L. For some combinations of agents and organisms, different methods gave different values for the proportion of isolates susceptible. Regardless of methodology, for H. influenzae, the most active antimicrobials based on proportion of strains susceptible were ciprofloxacin (100%) and cefpodoxime (98.5-100%). For M. catarrhalis, the most active agents were azithromycin, cefaclor, cefixime, cefpodoxime, cefuroxime, ciprofloxacin, clarithromycin and loracarbef (100% each); the least active was ampicillin. Against penicillin-sensitive and -resistant pneumococci, the activity was not significantly different for azithromycin and clarithromycin (93.4-100%) and ciprofloxacin (MIC90 2.0 and 1.5 mg/L, respectively) but was different for cefuroxime (99.3% and 31.6%, respectively), cefaclor (MIC90 0.75 and > or = 256 mg/L, respectively), cefpodoxime (MIC90 0.047 and 1.5 mg/L, respectively) and loracarbef (MIC90 0.75 and > or = 256 mg/L, respectively). This study indicates the increasing incidence, in Canada, of beta-lactamase resistance in H. influenzae and M. catarrhalis and penicillin resistance in S. pneumoniae.

Structure and Function of Task-Oriented Social Networks

DTIC Science & Technology

2015-01-05

sizes can cause instability in correlation measures. A recently developed bivariate measure of  association, Maximal Information Coefficient ( MIC ...promises to simultaneously discover if two  variables have: a) any association, b) a functional relationship, and c) a non­linear  relationship. The  MIC ...problems with the values reported by standard and rank  correlation measures. In our first study [15], we illustrated the use of  MIC  using a variety of

E. coli encoding blaNDM-5 associated with community-acquired UTI cases with unusual MIC creep like phenomenon against Imipenem.

PubMed

Gajamer, Varsha Rani; Bhattacharjee, Amitabha; Paul, Deepjyoti; Deshamukhya, Chandrayee; Singh, Ashish Kr; Pradhan, Nilu; Tiwari, Hare Krishna

2018-05-15

Carbapenemase-producing Escherichia coli are of major clinical concern. The present study aimed to identify NDM-5 producing E.coli associated with community-acquired urinary tract infection, co-harboring ESBL genes and a pattern of imipenem MIC creep. A total of 973 urine samples were collected from females of age between 18-49 diagnosed with UTI. Isolates were identified by standard microbiological procedures. Presence of bla NDM and ESBL genes was determined by PCR assay and sequencing.PCR based replicon typing was performed. Plasmid stability of all bla producers and their transformants study were analyzed by serial passages and MIC creep phenomenon was analysed by studying revertants. Among 34 bla NDM-5 positive E.coli isolates, 21 isolates co harbored bla CTX-M-15 , followed by multiple combinations of genes. The study revealed diverse types of plasmids type viz; HI1, I1, FIA+FIB, FIA and Y. The strains showed progressive plasmid loss after 31 passages.Twenty-eight isolates mostly had MIC value of 0.5μg/ml and 1μg/ml against imipenem, ertapenem and meropenem. However, on studying the MIC creep activity; the MIC was found elevated from 0.5ug/ml to 64μg/ml and from 1μg/ml to 128μg/ml. While analyzing the revertants, MIC of most of the NDM positive isolates was reduced to 16μg/ml after the 30th serial passages. This study observed a unique phenotype of NDM producers which is not been reported earlier. In the current study, the observed phenomenon poses a global threat as these pathogens may evade phenotypic screening by routine laboratories. Copyright © 2018. Published by Elsevier Ltd.

In vitro susceptibility of filamentous fungi from mycotic keratitis to azole drugs.

PubMed

Shobana, C S; Mythili, A; Homa, M; Galgóczy, L; Priya, R; Babu Singh, Y R; Panneerselvam, K; Vágvölgyi, C; Kredics, L; Narendran, V; Manikandan, P

2015-03-01

The in vitro antifungal activities of azole drugs viz., itraconazole, voriconazole, ketoconazole, econazole and clotrimazole were investigated in order to evaluate their efficacy against filamentous fungi isolated from mycotic keratitis. The specimen collection was carried out from fungal keratitis patients attending Aravind eye hospital and Post-graduate institute of ophthalmology, Coimbatore, India and was subsequently processed for the isolation of fungi. The dilutions of antifungal drugs were prepared in RPMI 1640 medium. Minimum inhibitory concentrations (MICs) were determined and MIC50 and MIC90 were calculated for each drug tested. A total of 60 fungal isolates were identified as Fusarium spp. (n=30), non-sporulating moulds (n=9), Aspergillus flavus (n=6), Bipolaris spp. (n=6), Exserohilum spp. (n=4), Curvularia spp. (n=3), Alternaria spp. (n=1) and Exophiala spp. (n=1). The MICs of ketoconazole, clotrimazole, voriconazole, econazole and itraconazole for all the fungal isolates ranged between 16 μg/mL and 0.03 μg/mL, 4 μg/mL and 0.015 μg/mL, 8 μg/mL and 0.015 μg/mL, 8 μg/mL and 0.015 μg/mL and 32 μg/mL and 0.06 μg/mL respectively. From the MIC50 and MIC90 values, it could be deciphered that in the present study, clotrimazole was more active against the test isolates at lower concentrations (0.12-5 μg/mL) when compared to other drugs tested. The results suggest that amongst the tested azole drugs, clotrimazole followed by voriconazole and econazole had lower MICs against moulds isolated from mycotic keratitis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Surveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates.

PubMed

Talbot, Jessica J; Subedi, Shradha; Halliday, Catriona L; Hibbs, David E; Lai, Felcia; Lopez-Ruiz, Francisco J; Harper, Lincoln; Park, Robert F; Cuddy, William S; Biswas, Chayanika; Cooley, Louise; Carter, Dee; Sorrell, Tania C; Barrs, Vanessa R; Chen, Sharon C-A

2018-05-29

The prevalence of azole resistance in Aspergillus fumigatus is uncertain in Australia. Azole exposure may select for resistance. We investigated the frequency of azole resistance in a large number of clinical and environmental isolates. A. fumigatus isolates [148 human, 21 animal and 185 environmental strains from air (n = 6) and azole-exposed (n = 64) or azole-naive (n = 115) environments] were screened for azole resistance using the VIPcheck™ system. MICs were determined using the Sensititre™ YeastOne YO10 assay. Sequencing of the Aspergillus cyp51A gene and promoter region was performed for azole-resistant isolates, and cyp51A homology protein modelling undertaken. Non-WT MICs/MICs at the epidemiological cut-off value of one or more azoles were observed for 3/148 (2%) human isolates but not amongst animal, or environmental, isolates. All three isolates grew on at least one azole-supplemented well based on VIPcheck™ screening. For isolates 9 and 32, the itraconazole and posaconazole MICs were 1 mg/L (voriconazole MICs 0.12 mg/L); isolate 129 had itraconazole, posaconazole and voriconazole MICs of >16, 1 and 8 mg/L, respectively. Soil isolates from azole-exposed and azole-naive environments had similar geometric mean MICs of itraconazole, posaconazole and voriconazole (P > 0.05). A G54R mutation was identified in the isolates exhibiting itraconazole and posaconazole resistance, and the TR34/L98H mutation in the pan-azole-resistant isolate. cyp51A modelling predicted that the G54R mutation would prevent binding of itraconazole and posaconazole to the haem complex. Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

PubMed Central

Skipworth, R J E; Deans, D A C; Tan, B H L; Sangster, K; Paterson-Brown, S; Brown, D A; Hunter, M; Breit, S N; Ross, J A; Fearon, K C H

2010-01-01

Background: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). Methods: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of ⩾10 mg l–1 or modified Glasgow prognostic score (mGPS) of ⩾1), and nutritional status were assessed in newly diagnosed OGC patients (n=293). Healthy volunteers (n=35) served as controls. Results: MIC-1 was elevated in patients (median=1371 pg ml–1; range 141–39 053) when compared with controls (median=377 pg ml–1; range 141–3786; P<0.001). Patients with gastric tumours (median=1592 pg ml–1; range 141–12 643) showed higher MIC-1 concentrations than patients with junctional (median=1337 pg ml–1; range 383–39 053) and oesophageal tumours (median=1180 pg ml–1; range 258–31 184; P=0.015). Patients showed a median weight loss of 6.4% (range 0.0–33.4%), and 42% of patients had an mGPS of ⩾1 or plasma CRP of ⩾10 mg l–1 (median=9 mg l–1; range 1–200). MIC-1 correlated positively with disease stage (r2=0.217; P<0.001), age (r2=0.332; P<0.001), CRP (r2=0.314; P<0.001), and mGPS (r2=0.336; P<0.001), and negatively with Karnofsky Performance Score (r2=−0.269; P<0.001). However, although MIC-1 correlated weakly with dietary intake (r2=0.157; P=0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median=204 days; 95% CI 157–251) when compared with patients with MIC-1 levels in the lower three quartiles (median=316 days; 95% CI 259–373; P=0.036), but MIC-1 was not an independent prognostic indicator. Conclusions: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC. PMID:20104227

Cytotoxicity and anti-Sporothrix brasiliensis activity of the Origanum majorana Linn. oil.

PubMed

Waller, Stefanie Bressan; Madrid, Isabel Martins; Ferraz, Vanny; Picoli, Tony; Cleff, Marlete Brum; de Faria, Renata Osório; Meireles, Mário Carlos Araújo; de Mello, João Roberto Braga

The study aimed to evaluate the anti-Sporothrix sp. activity of the essential oil of Origanum majorana Linn. (marjoram), its chemical analysis, and its cytotoxic activity. A total of 18 fungal isolates of Sporothrix brasiliensis (n: 17) from humans, dogs and cats, and a standard strain of Sporothrix schenckii (n: 1) were tested using the broth microdilution technique (Clinical and Laboratory Standard Institute - CLSI M27-A3) and the results were expressed in minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC). The MIC 50 and MIC 90 of itraconazole against S. brasiliensis were 2μg/mL and 8μg/mL, respectively, and the MFC 50 and MFC 90 were 2μg/mL and >16μg/mL, respectively, with three S. brasiliensis isolates resistant to antifungal. S. schenckii was sensitive at MIC of 1μg/mL and MFC of 8μg/mL. For the oil of O. majorana L., all isolates were susceptible to MIC of ≤2.25-9mg/mL and MFC of ≤2.25-18mg/mL. The MIC 50 and MIC 90 were ≤2.25mg/mL and 4.5mg/mL, respectively, and the MFC 50/90 values were twice more than the MIC. Twenty-two compounds were identified by gas chromatography with a flame ionization detector (CG-FID) and 1,8-cineole and 4-terpineol were the majority. Through the colorimetric (MTT) assay, the toxicity was observed in 70-80% of VERO cells between 0.078 and 5mg/mL. For the first time, the study demonstrated the satisfactory in vitro anti-Sporothrix sp. activity of marjoram oil and further studies are needed to ensure its safe and effective use. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Chemical Profile, Antibacterial and Antioxidant Activity of Algerian Citrus Essential Oils and Their Application in Sardina pilchardus

PubMed Central

Djenane, Djamel

2015-01-01

Stored fish are frequently contaminated by foodborne pathogens. Lipid oxidation and microbial growth during storage are also important factors in the shelf-life of fresh fish. In order to ensure the safety of fish items, there is a need for control measures which are effective through natural inhibitory antimicrobials. It is also necessary to determine the efficacy of these products for fish protection against oxidative damage, to avoid deleterious changes and loss of commercial and nutritional value. Some synthetic chemicals used as preservatives have been reported to cause harmful effects to the environment and the consumers. The present investigation reports on the extraction by hydrodistillation and the chemical composition of three citrus peel essential oils (EOs): orange (Citrus sinensis L.), lemon (Citrus limonum L.) and bergamot (Citrus aurantium L.) from Algeria. Yields for EOs were between 0.50% and 0.70%. The chemical composition of these EOs was determined by gas chromatography coupled with mass spectrometry (GC/MS). The results showed that the studied oils are made up mainly of limonene (77.37%) for orange essential oil (EO); linalyl acetate (37.28%), linalool (23.36%), for bergamot EO; and finally limonene (51.39%), β-pinene (17.04%) and γ-terpinene (13.46%) for lemon EO. The in vitro antimicrobial activity of the EOs was evaluated against Staphylococcus aureus (S. aureus) using the agar diffusion technique. Results revealed that lemon EO had more antibacterial effects than that from other EOs. Minimal inhibitory concentrations (MICs) showed a range of 0.25–0.40 μL/mL. Lemon and bergamot citrus peel EOs were added at 1 × MIC and 4 × MIC values to Sardina pilchardus (S. pilchardus) experimentally inoculated with S. aureus at a level of 3.5 log10 CFU/g and stored at 8 ± 1 °C. The results obtained revealed that the 4 × MIC value of bergamot reduced completely the growth of S. aureus from day 2 until the end of storage. The presence of EOs significantly extended lipid stability. Samples treated with bergamot EO displayed greater antioxidant activity than lemon EO. In fact, the oxidation rate is inversely proportional to the concentration of EO. At 1 × MIC and 4 × MIC values of bergamot EO, the levels of malonaldehyde compared to the control samples were 1.66 and 1.28 mg malonaldehyde/kg at the end of storage, corresponding to inhibition percentages of 42.76% and 55.87%, respectively. These results suggest the possibility that citrus EOs could be used as a way of combating the growth of common causes of food poisoning and used as potent natural preservatives to contribute to the reduction of lipid oxidation in sardines. PMID:28231199

Chemical Profile, Antibacterial and Antioxidant Activity of Algerian Citrus Essential Oils and Their Application in Sardina pilchardus.

PubMed

Djenane, Djamel

2015-06-05

Stored fish are frequently contaminated by foodborne pathogens. Lipid oxidation and microbial growth during storage are also important factors in the shelf-life of fresh fish. In order to ensure the safety of fish items, there is a need for control measures which are effective through natural inhibitory antimicrobials. It is also necessary to determine the efficacy of these products for fish protection against oxidative damage, to avoid deleterious changes and loss of commercial and nutritional value. Some synthetic chemicals used as preservatives have been reported to cause harmful effects to the environment and the consumers. The present investigation reports on the extraction by hydrodistillation and the chemical composition of three citrus peel essential oils (EOs): orange ( Citrus sinensis L.), lemon ( Citrus limonum L.) and bergamot ( Citrus aurantium L.) from Algeria. Yields for EOs were between 0.50% and 0.70%. The chemical composition of these EOs was determined by gas chromatography coupled with mass spectrometry (GC/MS). The results showed that the studied oils are made up mainly of limonene (77.37%) for orange essential oil (EO); linalyl acetate (37.28%), linalool (23.36%), for bergamot EO; and finally limonene (51.39%), β-pinene (17.04%) and γ-terpinene (13.46%) for lemon EO. The in vitro antimicrobial activity of the EOs was evaluated against Staphylococcus aureus ( S . aureus ) using the agar diffusion technique. Results revealed that lemon EO had more antibacterial effects than that from other EOs. Minimal inhibitory concentrations (MICs) showed a range of 0.25-0.40 μL/mL. Lemon and bergamot citrus peel EOs were added at 1 × MIC and 4 × MIC values to Sardina pilchardus ( S . pilchardus ) experimentally inoculated with S. aureus at a level of 3.5 log 10 CFU/g and stored at 8 ± 1 °C. The results obtained revealed that the 4 × MIC value of bergamot reduced completely the growth of S. aureus from day 2 until the end of storage. The presence of EOs significantly extended lipid stability. Samples treated with bergamot EO displayed greater antioxidant activity than lemon EO. In fact, the oxidation rate is inversely proportional to the concentration of EO. At 1 × MIC and 4 × MIC values of bergamot EO, the levels of malonaldehyde compared to the control samples were 1.66 and 1.28 mg malonaldehyde/kg at the end of storage, corresponding to inhibition percentages of 42.76% and 55.87%, respectively. These results suggest the possibility that citrus EOs could be used as a way of combating the growth of common causes of food poisoning and used as potent natural preservatives to contribute to the reduction of lipid oxidation in sardines.

In-vitro activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota.

PubMed

Weintraub, Andrej; Rashid, Mamun-Ur; Nord, Carl Erik

2016-12-01

Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC 50 , 0.008 mg/L) and Lactobacilli (MIC 50 , 0.008 mg/L). The MIC 50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of formulas for calculating critical concentration by the agar diffusion method.

PubMed Central

Drugeon, H B; Juvin, M E; Caillon, J; Courtieu, A L

1987-01-01

The critical concentration of antibiotic was calculated by using the agar diffusion method with disks containing different charges of antibiotic. It is currently possible to use different calculation formulas (based on Fick's law) devised by Cooper and Woodman (the best known) and by Vesterdal. The results obtained with the formulas were compared with the MIC results (obtained by the agar dilution method). A total of 91 strains and two cephalosporins (cefotaxime and ceftriaxone) were studied. The formula of Cooper and Woodman led to critical concentrations that were higher than the MIC, but concentrations obtained with the Vesterdal formula were closer to the MIC. The critical concentration was independent of method parameters (dilution, for example). PMID:3619419

Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens

PubMed Central

Fyfe, Corey; O’Brien, William; Hackel, Meredith; Minyard, Mary Beth; Waites, Ken B.; Dubois, Jacques; Murphy, Timothy M.; Slee, Andrew M.; Weiss, William J.; Sutcliffe, Joyce A.

2017-01-01

ABSTRACT TP-271 is a novel, fully synthetic fluorocycline antibiotic in clinical development for the treatment of respiratory infections caused by susceptible and multidrug-resistant pathogens. TP-271 was active in MIC assays against key community respiratory Gram-positive and Gram-negative pathogens, including Streptococcus pneumoniae (MIC90 = 0.03 µg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC90 = 0.25 µg/ml), methicillin-resistant S. aureus (MRSA; MIC90 = 0.12 µg/ml), Streptococcus pyogenes (MIC90 = 0.03 µg/ml), Haemophilus influenzae (MIC90 = 0.12 µg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 µg/ml). TP-271 showed activity (MIC90 = 0.12 µg/ml) against community-acquired MRSA expressing Panton-Valentine leukocidin (PVL). MIC90 values against Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae were 0.004, 1, and 4 µg/ml, respectively. TP-271 was efficacious in neutropenic and immunocompetent animal pneumonia models, generally showing, compared to the burden at the start of dosing, ~2 to 5 log10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log10 CFU reductions when given orally (p.o.). TP-271 was potent against key community-acquired bacterial pneumonia (CABP) pathogens and was minimally affected, or unaffected, by tetracycline-specific resistance mechanisms and fluoroquinolone or macrolide drug resistance phenotypes. IMPORTANCE Rising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed for use in the empirical treatment of the most severe forms of this disease. TP-271 is a promising new fluorocycline antibiotic demonstrating in vitro potency and nonclinical efficacy by intravenous and oral administration against the major pathogens associated with moderate to severe CABP. PMID:28251179

[Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001].

PubMed

Yamaguchi, Keizo; Ishii, Yoshikazu; Iinuma, Yoshitsugu; Yamanaka, Kiyoharu; Ichiyama, Satoshi; Watanabe, Naoki; Uehara, Nobuyuki; Kaku, Mitsuo; Kurokawa, Yukinori; Hayashi, Mutsumu; Hirakata, Yoichi

2003-12-01

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.

Improved Detection of Candida sp. fks Hot Spot Mutants by Using the Method of the CLSI M27-A3 Document with the Addition of Bovine Serum Albumin▿†

PubMed Central

Garcia-Effron, Guillermo; Park, Steven; Perlin, David S.

2011-01-01

Echinocandins are highly bound to serum proteins, altering their antifungal properties. The addition of 50% human serum to the MIC assay improves the identification of echinocandin-resistant Candida spp. harboring fks hot spot mutations. However, this modification cannot readily be applied to the method of the CLSI M27-A3 document due to safety and standardization difficulties. The aim of this study was to evaluate commercial bovine serum albumin (BSA) as a safe and standardized alternative to human serum. A collection of 28 echinocandin-susceptible strains, 10 Candida parapsilosis sensu lato strains (with naturally reduced echinocandin susceptibility), and 40 FKS hot spot mutants was used in this work. When RPMI 1640 was used for susceptibility testing, wild-type strains and fks mutants showed MIC range overlaps (−2, −1, and −3 2-fold-dilution steps separated these populations for anidulafungin, caspofungin, and micafungin, respectively). On the other hand, the addition of BSA to RPMI 1640 differentially increased echinocandin MIC values for these groups of strains, allowing better separation between populations, with no MIC range overlaps for any of the echinocandin drugs tested. Moreover, the use of RPMI-BSA reduced the number of fks hot spot mutant isolates for which MIC values were less than or equal to the upper limit for the wild type (very major errors) from 9, 2, and 7 with RPMI alone to 3, 0, and 3 for anidulafungin, caspofungin, and micafungin, respectively. When RPMI-BSA was used to study the susceptibility of C. parapsilosis sensu lato species to echinocandins, the strains behaved as anidulafungin- and micafungin-resistant isolates (MIC, ≥8 μg/ml). These data support the need for a revision of the CLSI protocol for in vitro testing of echinocandin susceptibility in order to identify all or most of the fks hot spot mutants. Also, caspofungin could be used as a surrogate marker of reduced susceptibility to echinocandins. PMID:21383097

En Route towards European Clinical Breakpoints for Veterinary Antimicrobial Susceptibility Testing: A Position Paper Explaining the VetCAST Approach.

PubMed

Toutain, Pierre-Louis; Bousquet-Mélou, Alain; Damborg, Peter; Ferran, Aude A; Mevius, Dik; Pelligand, Ludovic; Veldman, Kees T; Lees, Peter

2017-01-01

VetCAST is the EUCAST sub-committee for Veterinary Antimicrobial Susceptibility Testing. Its remit is to define clinical breakpoints (CBPs) for antimicrobial drugs (AMDs) used in veterinary medicine in Europe. This position paper outlines the procedures and reviews scientific options to solve challenges for the determination of specific CBPs for animal species, drug substances and disease conditions. VetCAST will adopt EUCAST approaches: the initial step will be data assessment; then procedures for decisions on the CBP; and finally the release of recommendations for CBP implementation. The principal challenges anticipated by VetCAST are those associated with the differing modalities of AMD administration, including mass medication, specific long-acting product formulations or local administration. Specific challenges comprise mastitis treatment in dairy cattle, the range of species and within species breed considerations and several other variable factors not relevant to human medicine. Each CBP will be based on consideration of: (i) an epidemiological cut-off value (ECOFF) - the highest MIC that defines the upper end of the wild-type MIC distribution; (ii) a PK/PD breakpoint obtained from pre-clinical pharmacokinetic data [this PK/PD break-point is the highest possible MIC for which a given percentage of animals in the target population achieves a critical value for the selected PK/PD index ( f AUC/MIC or f T > MIC)] and (iii) when possible, a clinical cut-off, that is the relationship between MIC and clinical cure. For the latter, VetCAST acknowledges the paucity of such data in veterinary medicine. When a CBP cannot be established, VetCAST will recommend use of ECOFF as surrogate. For decision steps, VetCAST will follow EUCAST procedures involving transparency, consensus and independence. VetCAST will ensure freely available dissemination of information, concerning standards, guidelines, ECOFF, PK/PD breakpoints, CBPs and other relevant information for AST implementation. Finally, after establishing a CBP, VetCAST will promulgate expert comments and/or recommendations associated with CBPs to facilitate their sound implementation in a clinical setting.

En Route towards European Clinical Breakpoints for Veterinary Antimicrobial Susceptibility Testing: A Position Paper Explaining the VetCAST Approach

PubMed Central

Toutain, Pierre-Louis; Bousquet-Mélou, Alain; Damborg, Peter; Ferran, Aude A.; Mevius, Dik; Pelligand, Ludovic; Veldman, Kees T.; Lees, Peter

2017-01-01

VetCAST is the EUCAST sub-committee for Veterinary Antimicrobial Susceptibility Testing. Its remit is to define clinical breakpoints (CBPs) for antimicrobial drugs (AMDs) used in veterinary medicine in Europe. This position paper outlines the procedures and reviews scientific options to solve challenges for the determination of specific CBPs for animal species, drug substances and disease conditions. VetCAST will adopt EUCAST approaches: the initial step will be data assessment; then procedures for decisions on the CBP; and finally the release of recommendations for CBP implementation. The principal challenges anticipated by VetCAST are those associated with the differing modalities of AMD administration, including mass medication, specific long-acting product formulations or local administration. Specific challenges comprise mastitis treatment in dairy cattle, the range of species and within species breed considerations and several other variable factors not relevant to human medicine. Each CBP will be based on consideration of: (i) an epidemiological cut-off value (ECOFF) – the highest MIC that defines the upper end of the wild-type MIC distribution; (ii) a PK/PD breakpoint obtained from pre-clinical pharmacokinetic data [this PK/PD break-point is the highest possible MIC for which a given percentage of animals in the target population achieves a critical value for the selected PK/PD index (fAUC/MIC or fT > MIC)] and (iii) when possible, a clinical cut-off, that is the relationship between MIC and clinical cure. For the latter, VetCAST acknowledges the paucity of such data in veterinary medicine. When a CBP cannot be established, VetCAST will recommend use of ECOFF as surrogate. For decision steps, VetCAST will follow EUCAST procedures involving transparency, consensus and independence. VetCAST will ensure freely available dissemination of information, concerning standards, guidelines, ECOFF, PK/PD breakpoints, CBPs and other relevant information for AST implementation. Finally, after establishing a CBP, VetCAST will promulgate expert comments and/or recommendations associated with CBPs to facilitate their sound implementation in a clinical setting. PMID:29326661

Levofloxacin Efflux and smeD in Clinical Isolates of Stenotrophomonas maltophilia.

PubMed

Chong, So Young; Lee, Kyungwon; Chung, Hae-Sun; Hong, Seong Geun; Suh, Younghee; Chong, Yunsop

2017-03-01

Trimethoprim-sulfamethoxazole is the first-line antimicrobial combination for Stenotrophomonas maltophilia infections. However, allergy or intolerance and increasing resistance limit the use of trimethoprim-sulfamethoxazole. Quinolones can be used as an alternative therapeutic option, but resistance can emerge rapidly during therapy. We analyzed the contribution of SmeABC and SmeDEF efflux pumps to levofloxacin resistance in clinical isolates of S. maltophilia. Nonduplicate clinical isolates of S. maltophilia were collected in 2010 from 11 university hospitals (n = 102). Fifty-five levofloxacin nonsusceptible (minimum inhibitory concentration [MIC] ≥4 μg/ml) and 47 susceptible (MIC ≤2 μg/ml) isolates were tested for efflux pump overexpression. Real-time reverse transcription-PCR was performed for amplification and quantification of smeB, smeC, smeD, and smeF mRNA. To determine which antimicrobials were affected by smeD overexpression, the growth rates of a levofloxacin-susceptible S. maltophilia isolate were compared by measuring absorbance of antimicrobial-supplemented Luria-Bertani broth (LB) cultures with or without triclosan. Significant relationships between sme gene overexpression and resistance were observed for smeD against levofloxacin, smeC and smeF against ceftazidime, and smeC against ticarcillin-clavulanate. The mean MICs of moxifloxacin and tigecycline did not significantly differ for isolates with or without overexpression of smeB, smeC, and smeF, but were significantly higher for isolates with smeD overexpression. The mean MICs of amikacin were significantly higher for smeC or smeF overexpressing isolates. Increased growth of a levofloxacin-susceptible isolate was observed in LB with 1/2 MIC levofloxacin in the presence of triclosan. These data suggest that the expression of smeD plays a role in levofloxacin resistance in S. maltophilia.

Prospective Randomized Controlled Study on the Efficacy of Multimedia Informed Consent for Patients Scheduled to Undergo Green-Light High-Performance System Photoselective Vaporization of the Prostate

PubMed Central

Ham, Dong Yeub; Choi, Woo Suk; Song, Sang Hoon; Ahn, Young-Joon; Park, Hyoung Keun; Kim, Hyeong Gon

2016-01-01

Purpose The aim of this study was to evaluate the efficacy of a multimedia informed consent (IC) presentation on the understanding and satisfaction of patients who were scheduled to receive 120-W green-light high-performance system photoselective vaporization of the prostate (HPS-PVP). Materials and Methods A multimedia IC (M-IC) presentation for HPS-PVP was developed. Forty men with benign prostatic hyperplasia who were scheduled to undergo HPS-PVP were prospectively randomized to a conventional written IC group (W-IC group, n=20) or the M-IC group (n=20). The allocated IC was obtained by one certified urologist, followed by a 15-question test (maximum score, 15) to evaluate objective understanding, and questionnaires on subjective understanding (range, 0~10) and satisfaction (range, 0~10) using a visual analogue scale. Results Demographic characteristics, including age and the highest level of education, did not significantly differ between the two groups. No significant differences were found in scores reflecting the objective understanding of HPS-PVP (9.9±2.3 vs. 10.6±2.8, p=0.332) or in subjective understanding scores (7.5±2.1 vs. 8.6±1.7, p=0.122); however, the M-IC group showed higher satisfaction scores than the W-IC group (7.4±1.7 vs. 8.4±1.5, p=0.033). After adjusting for age and educational level, the M-IC group still had significantly higher satisfaction scores. Conclusions M-IC did not enhance the objective knowledge of patients regarding this surgical procedure. However, it improved the satisfaction of patients with the IC process itself. PMID:27169129

In vitro activity and rodent efficacy of clinafloxacin for bovine and swine respiratory disease.

PubMed

Sweeney, Michael T; Quesnell, Rebecca; Tiwari, Raksha; Lemay, Mary; Watts, Jeffrey L

2013-01-01

Clinafloxacin is a broad-spectrum fluoroquinolone that was originally developed and subsequently abandoned in the late 1990s as a human health antibiotic for respiratory diseases. The purpose of this study was to investigate the activity of clinafloxacin as a possible treatment for respiratory disease in cattle and pigs. Minimum inhibitory concentration (MIC) values were determined using Clinical and Laboratory Standards Institute recommended procedures with recent strains from the Zoetis culture collection. Rodent efficacy was determined in CD-1 mice infected systemically or intranasally with bovine Mannheimia haemolytica or Pasteurella multocida, or swine Actinobacillus pleuropneumoniae, and administered clinafloxacin for determination of ED50 (efficacious dose-50%) values. The MIC90 values for clinafloxacin against bovine P. multocida, M. haemolytica, Histophilus somni, and M. bovis were 0.125, 0.5, 0.125, and 1 μg/ml, respectively, and the MIC90 values against swine P. multocida, A. pleuropneumoniae, S. suis, and M. hyopneumoniae were í0.03, í0.03, 0.125, and í0.008 μg/ml, respectively. Efficacy in mouse models showed average ED50 values of 0.019 mg/kg/dose in the bovine M. haemolytica systemic infection model, 0.55 mg/kg in the bovine P. multocida intranasal lung challenge model, 0.08 mg/kg/dose in the bovine P. multocida systemic infection model, and 0.7 mg/kg/dose in the swine A. pleuropneumoniae systemic infection model. Clinafloxacin shows good in vitro activity and efficacy in mouse models and may be a novel treatment alternative for the treatment of respiratory disease in cattle and pigs.

Antimicrobial activity and molecular docking studies of a novel anthraquinone from a marine-derived fungus Aspergillus versicolor.

PubMed

Wang, Weiyi; Chen, Ruixuan; Luo, Zhuhua; Wang, Wei; Chen, Jianming

2018-03-01

A novel anthraquinone, 2-(dimethoxymethyl)-1-hydroxyanthracene-9,10-dione (1), together with nine known compounds (2-10), were isolated from the fermentation of Aspergillus versicolor derived from deep sea sediment. Their structures were established through spectroscopic methods. Compound 1 exhibited strong inhibitory activities against MRSA ATCC 43300 and MRSA CGMCC 1.12409 (with MIC values of 3.9 and 7.8 μg/mL respectively) and moderate activities against tested strains of Vibrio (with MIC values ranging from 15.6 to 62.5 μg/mL). Compound 1 was subjected to molecular docking studies for inhibition of topoisomerase IV and AmpC β-lactamase enzymes indicating its usefulness as antimicrobial agent.

Escherichia coli Cell Surface Perturbation and Disruption Induced by Antimicrobial Peptides BP100 and pepR*

PubMed Central

Alves, Carla S.; Melo, Manuel N.; Franquelim, Henri G.; Ferre, Rafael; Planas, Marta; Feliu, Lidia; Bardají, Eduard; Kowalczyk, Wioleta; Andreu, David; Santos, Nuno C.; Fernandes, Miguel X.; Castanho, Miguel A. R. B.

2010-01-01

The potential of antimicrobial peptides (AMPs) as an alternative to conventional therapies is well recognized. Insights into the biological and biophysical properties of AMPs are thus key to understanding their mode of action. In this study, the mechanisms adopted by two AMPs in disrupting the Gram-negative Escherichia coli bacterial envelope were explored. BP100 is a short cecropin A-melittin hybrid peptide known to inhibit the growth of phytopathogenic Gram-negative bacteria. pepR, on the other hand, is a novel AMP derived from the dengue virus capsid protein. Both BP100 and pepR were found to inhibit the growth of E. coli at micromolar concentrations. Zeta potential measurements of E. coli incubated with increasing peptide concentrations allowed for the establishment of a correlation between the minimal inhibitory concentration (MIC) of each AMP and membrane surface charge neutralization. While a neutralization-mediated killing mechanism adopted by either AMP is not necessarily implied, the hypothesis that surface neutralization occurs close to MIC values was confirmed. Atomic force microscopy (AFM) was then employed to visualize the structural effect of the interaction of each AMP with the E. coli cell envelope. At their MICs, BP100 and pepR progressively destroyed the bacterial envelope, with extensive damage already occurring 2 h after peptide addition to the bacteria. A similar effect was observed for each AMP in the concentration-dependent studies. At peptide concentrations below MIC values, only minor disruptions of the bacterial surface occurred. PMID:20566635

Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study.

PubMed

de Castro, Ricardo Dias; de Souza, Trícia Murielly Pereira Andrade; Bezerra, Louise Morais Dornelas; Ferreira, Gabriela Lacet Silva; Costa, Edja Maria Melo de Brito; Cavalcanti, Alessandro Leite

2015-11-24

Limitations of antifungal agents used in the treatment of oral candidiasis, as the development of resistant strains, are known by the scientific community. In this context, the aim of this study was to evaluate the antifungal activity of thymol against Candida albicans, Candida tropicalis and Candida krusei strains and to determine its mode of action and synergistic effect when combined with the synthetic antifungal nystatin. The minimum inhibitory concentration (MIC) was determined using a microdilution technique, and the minimum fungicidal concentration (MFC) was determined via subculture sowing. The mode of action of thymol was established by verifying fungal growth in the presence of sorbitol or ergosterol. The fractional inhibitory concentration index (FIC) was determined using the checkerboard method. Thymol presented an antifungal effect, with MICs of 39 μg/mL for C. albicans and C. krusei and 78 μg/mL for C. tropicalis. The results of the antifungal test remained unchanged in the presence of sorbitol; however, the MIC value of thymol against C. albicans increased eight times (from 39.0 to 312.5 μg/mL) in presence of exogenous ergosterol. The combination of thymol and nystatin reduced the MIC values of both products by 87.4%, generating an FIC index of 0.25. Thymol was found to have a fungicidal effect on Candida species and a synergistic effect when combined with nystatin.

Activity of TDT 067 (Terbinafine in Transfersome) against Agents of Onychomycosis, as Determined by Minimum Inhibitory and Fungicidal Concentrations▿

PubMed Central

Ghannoum, Mahmoud; Isham, Nancy; Herbert, Jacqueline; Henry, William; Yurdakul, Sam

2011-01-01

TDT 067 is a novel carrier-based dosage form (liquid spray) of 15 mg/ml of terbinafine in Transfersome that has been developed to deliver terbinafine to the nail bed to treat onychomycosis. In this study, we report the in vitro activities of TDT 067 against dermatophytes, compared with those of the Transfersome vehicle, naked terbinafine, and commercially available terbinafine (1%) spray. The MICs of TDT 067 and comparators against 25 clinical strains each of Trichophyton rubrum, T. mentagrophytes, and Epidermophyton floccosum were determined according to the CLSI M38–A2 susceptibility method (2008). Minimum fungicidal concentrations (MFCs) were determined by subculturing visibly clear wells from the MIC microtiter plates. TDT 067 demonstrated potent activity against the dermatophyte strains tested, with an MIC range of 0.00003 to 0.015 μg/ml. Overall, TDT 067 MIC50 values (defined as the lowest concentrations to inhibit 50% of the strains tested) were 8-fold and 60-fold lower than those of naked terbinafine and terbinafine spray, respectively. The Transfersome vehicle showed minimal inhibitory activity. TDT 067 demonstrated lower MFC values for T. rubrum and E. floccosum than naked terbinafine and terbinafine spray. TDT 067 has more potent antifungal activity against dermatophytes that cause nail infection than conventional terbinafine preparations. The Transfersome vehicle appears to potentiate the antifungal activity of terbinafine. Clinical investigation of TDT 067 for the topical treatment of onychomycosis is warranted. PMID:21411586

Activity of TDT 067 (terbinafine in Transfersome) against agents of onychomycosis, as determined by minimum inhibitory and fungicidal concentrations.

PubMed

Ghannoum, Mahmoud; Isham, Nancy; Herbert, Jacqueline; Henry, William; Yurdakul, Sam

2011-05-01

TDT 067 is a novel carrier-based dosage form (liquid spray) of 15 mg/ml of terbinafine in Transfersome that has been developed to deliver terbinafine to the nail bed to treat onychomycosis. In this study, we report the in vitro activities of TDT 067 against dermatophytes, compared with those of the Transfersome vehicle, naked terbinafine, and commercially available terbinafine (1%) spray. The MICs of TDT 067 and comparators against 25 clinical strains each of Trichophyton rubrum, T. mentagrophytes, and Epidermophyton floccosum were determined according to the CLSI M38-A2 susceptibility method (2008). Minimum fungicidal concentrations (MFCs) were determined by subculturing visibly clear wells from the MIC microtiter plates. TDT 067 demonstrated potent activity against the dermatophyte strains tested, with an MIC range of 0.00003 to 0.015 μg/ml. Overall, TDT 067 MIC(50) values (defined as the lowest concentrations to inhibit 50% of the strains tested) were 8-fold and 60-fold lower than those of naked terbinafine and terbinafine spray, respectively. The Transfersome vehicle showed minimal inhibitory activity. TDT 067 demonstrated lower MFC values for T. rubrum and E. floccosum than naked terbinafine and terbinafine spray. TDT 067 has more potent antifungal activity against dermatophytes that cause nail infection than conventional terbinafine preparations. The Transfersome vehicle appears to potentiate the antifungal activity of terbinafine. Clinical investigation of TDT 067 for the topical treatment of onychomycosis is warranted.

Antimicrobial susceptibility of Brachyspira hyodysenteriae isolated from 21 Polish farms.

PubMed

Zmudzki, J; Szczotka, A; Nowak, A; Strzelecka, H; Grzesiak, A; Pejsak, Z

2012-01-01

Swine dysentery (SD) is a common disease among pigs worldwide, which contributes to major production losses. Antimicrobial susceptibility testing of B. hyodysenteriae, the etiological agent of SD, is mainly performed by the agar dilution method. This method has certain limitations due to difficulties in interpretation of results. The aim of this study was the analysis of antimicrobial susceptibility of Brachyspira hyodysenteriae (B. hyodysenteriae) Polish field isolates by broth microdilution procedure. The study was performed on 21 isolates of B. hyodysenteriae, collected between January 2006 to December 2010 from cases of swine dysentery. VetMIC Brachyspira panels with antimicrobial agents (tiamulin, valnemulin, doxycycline, lincomycin, tylosin and ampicillin) were used for susceptibility testing of B. hyodysenteriae. The minimal inhibitory concentration (MIC) was determined by the broth dilution procedure. The lowest antimicrobial activity was demonstrated for tylosin and lincomycin, with inhibition of bacterial growth using concentrations > 128 microg/ml and 32 microg/ml, respectively. In the case of doxycycline, the MIC values were < or = 2.0 microg/ml. No decreased susceptibility to tiamulin was found among the Polish isolates and MIC values for this antibiotic did not exceed 1.0 microg/ml. The results of the present study confirmed that Polish B. hyodysenteriae isolates were susceptible to the main antibiotics (tiamulin and valnemulin) used in treatment of swine dysentery. Further studies are necessary to evaluate a possible slow decrease in susceptibility to tiamulin and valnemulin of B. hyodysenteriae strains in Poland.

The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria.

PubMed

Laudy, Agnieszka E; Kulińska, Ewa; Tyski, Stefan

2017-01-11

The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO₄. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide) was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100-800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species.

PubMed

Chowdhary, Anuradha; Singh, Pradeep Kumar; Kathuria, Shallu; Hagen, Ferry; Meis, Jacques F

2015-12-01

We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

In vitro activities of nine peptide deformylase inhibitors and five comparator agents against respiratory and skin pathogens.

PubMed

Bowker, K E; Noel, A R; MacGowan, A P

2003-12-01

The activity of nine peptide deformylase (PDF) inhibitors undergoing clinical evaluation were compared with co-amoxiclav, levofloxacin, moxifloxacin, erythromycin and telithromycin against a range of respiratory and skin pathogens (n=166). The PDF inhibitor showed good activity against Streptococcus pneumoniae, Moxarella catarrhalis, Group A streptococci and Staphylococcus aureus irrespective of beta-lactam or fluoroquinolone susceptibility. Against Haemophilus influenzae, MIC(90) values were generally higher. BB-88488 was the most active compound. Overall these data suggest that PDF inhibitors are an interesting new class of antimicrobial worthy of further investigation in the treatment of respiratory tract and skin infections.

Alkylphenol Activity against Candida spp. and Microsporum canis: A Focus on the Antifungal Activity of Thymol, Eugenol and O-Methyl Derivatives.

PubMed

Fontenelle, Raquel O S; Morais, Selene M; Brito, Erika H S; Brilhante, Raimunda S N; Cordeiro, Rossana A; Lima, Ynayara C; Brasil, Nilce V G P S; Monteiro, André J; Sidrim, José J C; Rocha, Marcos F G

2011-07-29

In recent years there has been an increasing search for new antifungal compounds due to the side effects of conventional antifungal drugs and fungal resistance. The aims of this study were to test in vitro the activity of thymol, eugenol, estragole and anethole and some O-methyl-derivatives (methylthymol and methyleugenol) against Candida spp. and Microsporum canis. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC). The minimum fungicidal concentrations (MFC) for both Candida spp. and M. canis were found by subculturing each fungal suspension on potato dextrose agar. Thymol, methylthymol, eugenol, methyl-eugenol, anethole, estragole and griseofulvin respectively, presented the following MIC values against M. canis: 4.8-9.7; 78-150; 39; 78-150; 78-150; 19-39 µg/mL and 0.006-2.5 mg/mL. The MFC values for all compounds ranged from 9.7 to 31 µg/mL. Concerning Candida spp, thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and amphotericin, respectively, showed the following MIC values: 39; 620-1250; 150-620; 310-620; 620; 620-1250 and 0.25-2.0 mg/mL. The MFC values varied from 78 to 2500 µg/mL. All tested compounds thus showed in vitro antifungal activity against Candida spp. and M. canis. Therefore, further studies should be carried out to confirm the usefulness of these alkylphenols in vivo.

Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica.

PubMed

Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J J; Hesje, C E

2012-11-09

Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmacodynamic target attainment analysis against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia (CAP).

PubMed

Noreddin, Ayman M; Marras, Theodore K; Sanders, Kevin; Chan, Charles K N; Hoban, Daryl J; Zhanel, George G

2004-11-01

The pharmacokinetics and pharmacodynamics of levofloxacin in patients with respiratory infections such as community-acquired pneumonia (CAP) are poorly documented. This work aimed at assessing the pharmacodynamic target attainment against Streptococcus pneumoniae using levofloxacin 500 mg, 750 mg and 1000 mg administered once daily in plasma (P) and epithelial lining fluid (ELF) of hospitalized patients with community acquired pneumonia. The pharmacokinetics of levofloxacin in elderly (>/=65 years) compared with younger patients (<65 years) hospitalized with CAP were simulated. Susceptibility data with S. pneumoniae from our ongoing national surveillance study (Canadian Respiratory Organism Susceptibility Study-CROSS) were then used to produce pharmacodynamic indices of AUC(0-24)/MIC(all.) Monte Carlo simulations were then used to analyse target attainment of levofloxacin using doses of 500 mg, 750 mg and 1000 mg once daily to achieve free drug AUC(0-24)/MIC(all) >/= 30-100 versus S. pneumoniae in patients with CAP. Pharmacokinetics of levofloxacin simulated after 500 mg, 750 mg and 1000 mg once daily dosing resulted in levofloxacin volume of distribution: elderly patients = younger patients, while levofloxacin clearance was: elderly patients < younger patients. Levofloxacin t(1/2) values were longer in elderly patients (9.8 +/- 2.5h) than younger patients with CAP (7.4 +/- 2.5h). Free levofloxacin AUC(0-24) as well as AUC(0-24)/MIC(all) for S. pneumoniae were higher in elderly patients than younger patients. Monte Carlo simulation using levofloxacin 500 mg yielded probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in P and ELF (95.7% and 98.1%) in elderly and younger patients (72.7% and 80.6%) respectively. Levofloxacin 750 mg and 1000 mg once daily had probability of achieving free-drug AUC(0-24)/MIC(all) of 30 in P/ELF of 98.1%/98.6% and 99.2%/99.0%, respectively, in elderly patients compared with 89.9%/94.1% and 95.2%/96.5%, respectively, for younger patients. Probability of achieving of AUC(0-24)/MIC(all) of 100 in P or ELF was very low in both patient populations at different doses except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg once daily P/ELF of 78.5%/87.0%. We conclude that levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patients. Levofloxacin 750 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in both plasma and epithelial lining fluid in patients with CAP including younger patients. Levofloxacin 500 mg OD provides high probabilities of achieving free-drug AUC(0-24)/MIC(all) of 30 in elderly patients with CAP, although we favour the 750 mg dosing in these patients as well. Levofloxacin 750 mg OD results in high probability of pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae in patients with CAP.

In vitro activity of Schinus terebinthifolius (Brazilian pepper tree) on Candida tropicalis growth and cell wall formation.

PubMed

Alves, Lívia A; Freires, Irlan de A; de Souza, Tricia M P A; de Castro, Ricardo D

2012-01-01

The aim of this study was to evaluate the in vitro antifungal activity of Schinus terebinthifolius (Brazilian pepper tree) tincture on planktonic Candida tropicalis (ATCC 40042), which is a microorganism associated to oral cavity infections. Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) were determined through the microdilution technique. Possible action of the tincture on fungal cell wall formation was also studied by adding an osmotic protector (0.8M sorbitol) to the microplates. Nystatin was used as standard control and tests were performed in triplicate. S. terebinthifolius was found to have MIC and MFC values of 625 microg/mL on the strain assayed, whereas nystatin showed MIC and MFC of 6.25 microg/mL. Results suggest that S. terebinthifolius tincture acts on fungal cell walls, since the sorbitol test indicated a MIC of 1.250 microg/mL. It may be concluded that S. terebinthifolius has potential in vitro antifungal activity against C. tropicalis strains, and probably acts by inhibiting fungal cell wall formation.

Interpretation of positive results of a methacholine inhalation challenge and 1 week of inhaled bronchodilator use in diagnosing and treating cough-variant asthma.

PubMed

Irwin, R S; French, C T; Smyrnios, N A; Curley, F J

1997-09-22

In diagnosing cough due to asthma, methacholine chloride inhalation challenge (MIC) interpreted in a traditional fashion has been shown to have positive predictive values from 60% to 82%. To determine whether any features of positive results of an MIC or the results of a 1-week trial of inhaled beta-agonist therapy were helpful in predicting when the cough was due to asthma. The study design was a prospective, randomized, double-blind, placebo-controlled, crossover format performed in adult, nonsmoking subjects, who were referred for diagnosis and treatment of chronic cough. The subjects had no other respiratory complaints or medical conditions for which they were taking medications, the results of baseline spirometry and chest roentgenograms were normal, and the results of MIC were positive. After obtaining baseline data, including MICs on 2 separate days, objective cough counting, and self-assessment of cough severity using a visual analog scale, subjects were randomized to receive 2 inhalations (1.3 mg) of metaproterenol sulfate or placebo by metered dose inhaler attached to a spacer device every 4 hours while awake. At 1 week, data identical to baseline were collected, and subjects received the other metered dose inhaler for 7 days. At 1 week, data identical to baseline were collected. After completion of the protocol, subjects were followed up in the clinic to observe the final response of the cough to specific therapy. Based on the disappearance of the cough with specific therapy, the cough was due to asthma in 9 of 15 subjects and nonasthma in 6 of 15 subjects. Baseline data were similar between groups. With respect to MICs, there were no significant differences between groups in the cumulative dose of methacholine that provoked a 20% decrease in forced expiratory volume in 1 second from the postsaline baseline value (PD20 values), slopes of dose-response curves, and maximal-response plateaus. Cough severity significantly improved after 1 week of metaproterenol use compared with the severity of the cough at baseline (P = .03) and with placebo (P = .02) only in subjects with asthma. No matter how the results are analyzed, positive MIC results, without observing response to therapy, are only consistent with asthma as the cause of the cough. The results are only diagnostic of asthma when they are followed by a favorable response to asthma therapy. After 1 week of inhaled beta-agonist, only the cough due to cough-variant asthma is significantly better.

Polyketide derivatives from a marine-sponge-associated fungus Pestalotiopsis heterocornis.

PubMed

Lei, Hui; Lin, Xiuping; Han, Li; Ma, Jian; Dong, Kailin; Wang, Xingbo; Zhong, Jialiang; Mu, Yu; Liu, Yonghong; Huang, Xueshi

2017-10-01

Twelve previously undescribed polyketide derivatives, heterocornols A-L, and seven known analogues were isolated from a culture of the fungus Pestalotiopsis heterocornis associated with sponge. Their structures were elucidated by a comprehensive spectroscopic data analysis and CD Cotton effects. These compounds were evaluated for cytotoxic and antibacterial activities in vitro. Among them, heterocornols A-C, F-H, methyl-(2-formyl-3-hydroxyphenyl)propanoate, agropyrenol, and vaccinol G exhibited cytotoxicities against four human cancer cell lines with IC 50 values 15-100 μM, and they also showed antibacterial activities against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 25 to 100 μg/mL. Moreover, compounds heterocornol C, heterocornol G, agropyrenol, and vaccinol G showed weak antifungal activities against Candida parapsilosis and Cryptococcus neoformans with MIC values 100 μg/mL. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of ceftazidime and ciprofloxacin on biofilm formation in Proteus mirabilis rods.

PubMed

Kwiecińska-Piróg, Joanna; Bogiel, Tomasz; Gospodarek, Eugenia

2013-10-01

Proteus mirabilis rods are one of the most commonly isolated species of the Proteus genus from human infections, mainly those from the urinary tract and wounds. They are often related to biofilm structure formation. The bacterial cells of the biofilm are less susceptible to routinely used antimicrobials, making the treatment more difficult. The aim of this study was to evaluate quantitatively the influence of ceftazidime and ciprofloxacin on biofilm formation on the polyvinyl chloride surface by 42 P. mirabilis strains isolated from urine, purulence, wound swab and bedsore samples. It has been shown that ceftazidime and ciprofloxacin at concentrations equal to 1/4, 1/2 and 1 times their MIC values for particular Proteus spp. strains decrease their ability to form biofilms. Moreover, ciprofloxacin at concentrations equal to 1/4, 1/2 and 1 times their MIC values for particular P. mirabilis strains reduces biofilm formation more efficiently than ceftazidime at the corresponding concentration values.

Chemical composition and antibacterial activity of Lavandula coronopifolia essential oil against antibiotic-resistant bacteria.

PubMed

Ait Said, L; Zahlane, K; Ghalbane, I; El Messoussi, S; Romane, A; Cavaleiro, C; Salgueiro, L

2015-01-01

The aim of this study was to analyse the composition of the essential oil (EO) of Lavandula coronopifolia from Morocco and to evaluate its in vitro antibacterial activity against antibiotic-resistant bacteria isolated from clinical infections. The antimicrobial activity was assessed by a broth micro-well dilution method using multiresistant clinical isolates of 11 pathogenic bacteria: Klebsiella pneumoniae subsp. pneumoniae, Klebsiella ornithinolytica, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Providencia rettgeri, Citrobacter freundii, Hafnia alvei, Salmonella spp., Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus. The main compounds of the oil were carvacrol (48.9%), E-caryophyllene (10.8%) and caryophyllene oxide (7.7%). The oil showed activity against all tested strains with minimal inhibitory concentration (MIC) values ranging between 1% and 4%. For most of the strains, the MIC value was equivalent to the minimal bactericidal concentration value, indicating a clear bactericidal effect of L. coronopifolia EO.

Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii

PubMed Central

Wongpoowarak, Wibul; Wattanavijitkul, Thitima; Sukarnjanaset, Waroonrat; Samaeng, Maseetoh; Nawakitrangsan, Monchana; Ingviya, Natnicha

2016-01-01

Sulbactam is being considered as an alternative concomitant medication with other effective antibiotics for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections. Pathophysiological changes in critically ill patients with severe sepsis, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors in determining therapeutic success. The aims of this study were (i) to examine the population PK parameters and (ii) to assess the probability of target attainment (PTA) for sulbactam in patients with severe sepsis caused by A. baumannii. PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 4th day of drug administration in 27 patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the plasma drug concentration remained above the MIC (T>MIC) and 60% T>MIC. The central and peripheral volumes of distribution were 14.56 and 9.55 liters, respectively, and total clearances of sulbactam were 2.26 liters/h and 7.64 liters/h in patients aged >65 years and ≤65 years, respectively. The high PTAs (≥90%) for targets of 40% T>MIC and 60% T>MIC with a MIC of 4 μg/ml were observed when sulbactam was administered by a 4-h infusion of 1 g every 12 h and 1 g every 8 h, respectively. Sulbactam would be an alternative antibiotic option to coadminister with colistin for the treatment of infections caused by MDR A. baumannii. However, for pathogens with MICs of >4 μg/ml, higher dosage regimens of sulbactam are required. PMID:27671056

Heavy metal tolerance and removal potential in mixed-species biofilm.

PubMed

Grujić, Sandra; Vasić, Sava; Čomić, Ljiljana; Ostojić, Aleksandar; Radojević, Ivana

2017-08-01

The aim of the study was to examine heavy metal tolerance (Cd 2+ , Zn 2+ , Ni 2+ and Cu 2+ ) of single- and mixed-species biofilms (Rhodotorula mucilaginosa and Escherichia coli) and to determine metal removal efficiency (Cd 2+ , Zn 2+ , Ni 2+ , Cu 2+ , Pb 2+ and Hg 2+ ). Metal tolerance was quantified by crystal violet assay and results were confirmed by fluorescence microscopy. Metal removal efficiency was determined by batch biosorption assay. The tolerance of the mixed-species biofilm was higher than the single-species biofilms. Single- and mixed-species biofilms showed the highest sensitivity in the presence of Cu 2+ (E. coli-MIC 4 mg/ml, R. mucilaginosa-MIC 8 mg/ml, R. mucilaginosa/E. coli-MIC 64 mg/ml), while the highest tolerance was observed in the presence of Zn 2+ (E. coli-MIC 80 mg/ml, R. mucilaginosa-MIC 161 mg/ml, R. mucilaginosa-E. coli-MIC 322 mg/ml). The mixed-species biofilm exhibited better efficiency in removal of all tested metals than single-species biofilms. The highest efficiency in Cd 2+ removal was shown by the E. coli biofilm (94.85%) and R. mucilaginosa biofilm (97.85%), individually. The highest efficiency in Cu 2+ (99.88%), Zn 2+ (99.26%) and Pb 2+ (99.52%) removal was shown by the mixed-species biofilm. Metal removal efficiency was in the range of 81.56%-97.85% for the single- and 94.99%-99.88% for the mixed-species biofilm.

High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes.

PubMed

Falcón, Rocío; Martínez, Alba; Albert, Eliseo; Madrid, Silvia; Oltra, Rosa; Giménez, Estela; Soriano, Mario; Vinuesa, Víctor; Gozalbo, Daniel; Gil, María Luisa; Navarro, David

2016-05-01

Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index <60%) compared with those killed efficiently (killing index >70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Changes in In Vitro Susceptibility Patterns of Aspergillus to Triazoles and Correlation With Aspergillosis Outcome in a Tertiary Care Cancer Center, 1999-2015.

PubMed

Heo, Sang Taek; Tatara, Alexander M; Jiménez-Ortigosa, Cristina; Jiang, Ying; Lewis, Russell E; Tarrand, Jeffrey; Tverdek, Frank; Albert, Nathaniel D; Verweij, Paul E; Meis, Jacques F; Mikos, Antonios G; Perlin, David S; Kontoyiannis, Dimitrios P

2017-07-15

Azole-resistant aspergillosis in high-risk patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) is a cause of concern. We examined changes over time in triazole minimum inhibitory concentrations (MICs) of 290 sequential Aspergillus isolates recovered from respiratory sources during 1999-2002 (before introduction of the Aspergillus-potent triazoles voriconazole and posaconazole) and 2003-2015 at MD Anderson Cancer Center. We also tested for polymorphisms in ergosterol biosynthetic genes (cyp51A, erg3C, erg1) in the 37 Aspergillus fumigatus isolates isolated from both periods that had non-wild-type (WT) MICs. For the 107 patients with hematologic cancer and/or HSCT with invasive pulmonary aspergillosis, we correlated in vitro susceptibility with 42-day mortality. Non-WT MICs were found in 37 (13%) isolates and was only low level (MIC <8 mg/L) in all isolates. Higher-triazole MICs were more frequent in the second period and were Aspergillus-species specific, and only encountered in A. fumigatus. No polymorphisms in cyp51A, erg3C, erg1 genes were identified. There was no correlation between in vitro MICs with 42-day mortality in patients with invasive pulmonary aspergillosis, irrespective of antifungal treatment. Asian race (odds ratio [OR], 20.9; 95% confidence interval [CI], 2.5-173.5; P = .005) and azole exposure in the prior 3 months (OR, 9.6; 95% CI, 1.9-48.5; P = .006) were associated with azole resistance. Non-WT azole MICs in Aspergillus are increasing and this is associated with prior azole exposure in patients with hematologic cancer or HSCT. However, no correlation of MIC with outcome of aspergillosis was found in our patient cohort. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

In Vitro Antimicrobial Activity of Razupenem (SMP-601, PTZ601) against Anaerobic Bacteria▿

PubMed Central

Tran, Chau Minh; Tanaka, Kaori; Yamagishi, Yuka; Goto, Takatsugu; Mikamo, Hiroshige; Watanabe, Kunitomo

2011-01-01

We evaluated the in vitro antianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroides spp. (MIC90s of 2 μg/ml), with MIC90 values of 0.06, 0.03, and 0.5 μg/ml against Prevotella spp., Porphyromonas spp., and Fusobacterium spp., respectively. Clinical isolates of anaerobic Gram-positive cocci, Eggerthella spp., and Clostridium spp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml). PMID:21343447

Potential of tara (Caesalpinia spinosa) gallotannins and hydrolysates as natural antibacterial compounds.

PubMed

Aguilar-Galvez, Ana; Noratto, Giuliana; Chambi, Flor; Debaste, Frédéric; Campos, David

2014-08-01

Gallotannins obtained from tara pod extracts (EE) and from the products of acid hydrolysis for 4 and 9h (HE-4 and HE-9) were characterised for their composition, antioxidant activity, antimicrobial activity (AA) and minimum inhibitory concentration (MIC). Results of AA and MIC showed that EE exerted the highest inhibitory activity against Staphylococcus aureus, followed by Pseudomonas fluorescens; and among these bacteria, the antibacterial potency was enhanced after EE hydrolysis only against S. aureus. The lowest minimum inhibitory concentration (MIC) value (0.13mg gallic acid equivalent (GAE)/ml) was exerted by HE-4 against S. aureus. These results indicate that tara gallotannins have the potential to inhibit pathogenic bacteria with potential application in foods as antimicrobials and their AA can be enhanced by acid hydrolysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-Antibacterial Activity Relationships of Imidazolium-Type Ionic Liquid Monomers, Poly(ionic liquids) and Poly(ionic liquid) Membranes: Effect of Alkyl Chain Length and Cations.

PubMed

Zheng, Zhiqiang; Xu, Qiming; Guo, Jiangna; Qin, Jing; Mao, Hailei; Wang, Bin; Yan, Feng

2016-05-25

The structure-antibacterial activity relationship between the small molecular compounds and polymers are still elusive. Here, imidazolium-type ionic liquid (IL) monomers and their corresponding poly(ionic liquids) (PILs) and poly(ionic liquid) membranes were synthesized. The effect of chemical structure, including carbon chain length of substitution at the N3 position and charge density of cations (mono- or bis-imidazolium) on the antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was investigated by determination of minimum inhibitory concentration (MIC). The antibacterial activities of both ILs and PILs were improved with the increase of the alkyl chain length and higher charge density (bis-cations) of imidazolium cations. Moreover, PILs exhibited lower MIC values relative to the IL monomers. However, the antibacterial activities of PIL membranes showed no correlation to those of their analogous small molecule IL monomers and PILs, which increased with the charge density (bis-cations) while decreasing with the increase of alkyl chain length. The results indicated that antibacterial property studies on small molecules and homopolymers may not provide a solid basis for evaluating that in corresponding polymer membranes.

Anticandidal activity of cell extracts from 13 probiotic Lactobacillus strains and characterisation of lactic acid and a novel fatty acid derivative from one strain.

PubMed

Nyanzi, Richard; Awouafack, Maurice D; Steenkamp, Paul; Jooste, Piet J; Eloff, Jacobus N

2014-12-01

This study investigated the anti-Candida activity of methanol extracts from freeze-dried probiotic cells and the isolation of some constituents in the extracts. The MIC values of the probiotic methanol cell extracts against Candida albicans ranged between 1.25 and 5mg/ml after 48 h of incubation. However, Lactococcus latics subsp. lactis strain X and Lactobacillus casei strain B extracts had an MIC of 10mg/ml after 48 h of incubation. The extracts had fungistatic rather than fungicidal activity. These extracts had a much higher antifungal activity than antifungal compounds isolated from the growth medium by many other authors. This indicates that probiotics may also release antifungal compounds in their cells that could contribute to a therapeutic effect. Lactic acid (1) and 6-O-(α-D-glucopyranosyl)-1,6-di-O-pentadecanoyl-α-D-glucopyranose a novel fatty acid derivative (2) were isolated from methanol probiotic extracts and the structure of these compounds were elucidated using NMR (1 and 2D) and mass spectrometry (MS). Copyright © 2014 Elsevier Ltd. All rights reserved.

Antimicrobial effects of citrus sinensis peel extracts against periodontopathic bacteria: an in vitro study.

PubMed

Hussain, Khaja Amjad; Tarakji, Bassel; Kandy, Binu Purushothaman Panar; John, Jacob; Mathews, Jacob; Ramphul, Vandana; Divakar, Darshan Devang

2015-01-01

Use of plant extracts and phytochemicals with known antimicrobial properties may have great significance in therapeutic treatments. To assess the in vitro antimicrobial potential and also determine the minimum inhibitory concentration (MIC) of Citrus sinensis peel extracts with a view of searching a novel extract as a remedy for periodontal pathogens. Aqueous and ethanol (cold and hot) extracts prepared from peel of Citrus sinensis were screened for in vitro antimicrobial activity against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, using agar well diffusion method. The lowest concentration of every extract considered as the minimal inhibitory concentration (MIC) values were determined for both test organisms. Confidence level and level of significance were set at 95% and 5% respectively. Prevotella intermedia and Porphyromonas gingivalis were resistant to aqueous extracts while Aggregatibacter actinomycetemcomitans was inhibited at very high cncentrations. Hot ethanolic extracts showed significantly higher zone of inhibition than cold ethanolic extract. Minimum inhibitory concentration of hot and cold ethanolic extracts of Citrus sinensis peel ranged between 12-15 mg/ml against all three periodontal pathogens. Both extracts were found sensitive and contain compounds with therapeutic potential. Nevertheless, clinical trials on the effect of these plants are essential before advocating large-scale therapy.

Comparative pharmacodynamics of the new fluoroquinolone ABT492 and levofloxacin with Streptococcus pneumoniae in an in vitro dynamic model.

PubMed

Firsov, Alexander A; Alferova, Irene V; Smirnova, Maria V; Lubenko, Irene Yu; Portnoy, Yury A; Zinner, Stephen H

2005-05-01

The kinetics of killing of Streptococcus pneumoniae exposed to ABT492 or levofloxacin were compared. S. pneumoniae ATCC 49619 and four ciprofloxacin-resistant clinical isolates, S. pneumoniae 1149, 391, 79 and 804, were exposed to ABT492 and levofloxacin as a single dose in a dynamic model that simulates human pharmacokinetics of the quinolones. With S. pneumoniae ATCC 49619 eight-fold ranging AUC/MIC ratios (60-500 h) were simulated for each quinolone. In addition, two larger AUC/MICs, i.e., 1080 and 2150 h for ABT492 and 1460 and 3660 h for levofloxacin which correspond to 100 and 200 mg doses of ABT492 and 200 and 500 mg doses of levofloxacin, respectively, were mimicked. Each ciprofloxacin-resistant organism was exposed to the clinical doses of ABT492 (400 mg) and levofloxacin (500 mg); the respective AUC/MIC ratios were from 580 to 3470 h and from 28 to 110 h. At comparable AUC/MICs (from 60 to 500 h), regrowth of S. pneumoniae ATCC 49619 followed initial killing, and the times to regrowth were longer with levofloxacin than ABT492. However, no regrowth of S. pneumoniae ATCC 49619 occurred at the higher AUC/MICs of ABT492 (1080 and 2150 h) and levofloxacin (1460 and 3660 h). Killing of S. pneumoniae 1149, 391 and 79 without bacterial regrowth, was provided by ABT492 (AUC/MIC 3470, 2310 and 1160 h, respectively) but not levofloxacin (AUC/MIC 55, 110 and 28 h, respectively). Regrowth of S. pneumoniae 804 was observed with both ABT492 and levofloxacin (AUC/MIC 580 and 55 h, respectively). Areas between the control growth curve and the time-kill curve (ABBCs) for ABT492 against S. pneumoniae 1149, 391 and 79 were 2.6-4.2 times larger than the respective ABBCs for levofloxacin, whereas similar ABBCs were found with S. pneumoniae 804 exposed to both quinolones. These findings predict significantly greater efficacy of ABT492 than levofloxacin at clinically achievable AUC/MIC ratios against ciprofloxacin-resistant S. pneumoniae and similar efficacies of the two quinolones against susceptible organisms.

The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in Pediatric Patients: A Qualitative Systematic Review.

PubMed

Tkachuk, Stacey; Collins, Kyle; Ensom, Mary H H

2018-04-01

In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC. This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients. We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC. Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400. Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More research is needed to determine the relationships between vancomycin trough concentrations, AUC/MIC, and clinical outcomes.

Effect of biaxial versus coaxial microincision cataract surgery on optical quality of the cornea.

PubMed

Eliwa, Tamer Fahmy; Elsamkary, Mahmoud A; Hamza, Ismail

2015-06-01

Visual function is determined by a combination of the cornea, which has a larger effect and internal aberrations generated by the intraocular lens and those induced by the surgery. These corneal refractive changes are related to the location and size of the corneal incision. The smaller the incision, the lower the aberrations and the better the optical quality. To compare the effect of uneventful coaxial versus biaxial microincision cataract surgery (MICS) on the corneal aberrations. Retrospective interventional nonrandomized comparative case study comprised 40 eyes of 36 patients with primary senile cataract. They were divided into two groups: Group I (20 eyes) had operated by biaxial MICS and Group II (20 eyes) had operated by coaxial MICS. Each group were assessed by corneal topography and wavefront analysis over 6 mm pupil size preoperatively and 1-month postoperatively. Statistical analysis was performed using SPSS for Windows (version 17.0.1, SPSS, Inc.). The paired t-test was used to compare the mean values of corneal aberrations preoperatively and 1-month postoperatively in each group. There was a significant increase in trefoil and quatrefoil in biaxial MICS (P = 0.063, 0.032 respectively) while other aberrations insignificantly changed. The coaxial MICS showed a significant increase in root mean square (RMS) of total high order aberrations (HOAs) (P = 0.02) and coma (0.028), but not the others. In comparison to each other, there was the insignificant difference as regards astigmatism, RMS of individual and total HOAs. Coaxial and biaxial MICS are neutral on corneal astigmatism and aberrations.

Synergic activity, for anaerobes, of trovafloxacin with clindamycin or metronidazole: chequerboard and time-kill methods.

PubMed

Ednie, L M; Credito, K L; Khantipong, M; Jacobs, M R; Appelbaum, P C

2000-05-01

Chequerboard titrations were used to test the activity of trovafloxacin, alone and in combination with clindamycin or metronidazole, against 156 Gram-positive or Gram-negative anaerobes, including 47 Bacteroides fragilis group, 36 Prevotella spp., 26 fusobacteria, 21 peptostreptococci and 26 clostridia. MIC50/MIC90 values (mg/L) of each drug alone against all 156 strains were: trovafloxacin, 0.5/1; clindamycin, 0.25/2; metronidazole, 1/2. Synergy (FIC indices 0. 5-2.0); no antagonism (FIC indices >4.0) was seen. In addition, synergy was tested by time-kill methodology for each of the above combinations against 12 Gram-positive or Gram-negative strains. Results indicated that synergy (defined as a >/= 2 log(10) decrease in cfu/mL at 48 h compared with the more active drug alone) was found between trovafloxacin at or below the MIC and both clindamycin and metronidazole at or below the MIC in one strain each of Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella intermedia, Fusobacterium varium, Peptostreptococcus asaccharolyticus and Clostridium bifermentans. Synergy between trovafloxacin (

Time-lapse ERT interpretation methodology for leachate injection monitoring based on multiple inversions and a clustering strategy (MICS)

NASA Astrophysics Data System (ADS)

Audebert, M.; Clément, R.; Touze-Foltz, N.; Günther, T.; Moreau, S.; Duquennoi, C.

2014-12-01

Leachate recirculation is a key process in municipal waste landfills functioning as bioreactors. To quantify the water content and to assess the leachate injection system, in-situ methods are required to obtain spatially distributed information, usually electrical resistivity tomography (ERT). This geophysical method is based on the inversion process, which presents two major problems in terms of delimiting the infiltration area. First, it is difficult for ERT users to choose an appropriate inversion parameter set. Indeed, it might not be sufficient to interpret only the optimum model (i.e. the model with the chosen regularisation strength) because it is not necessarily the model which best represents the physical process studied. Second, it is difficult to delineate the infiltration front based on resistivity models because of the smoothness of the inversion results. This paper proposes a new methodology called MICS (multiple inversions and clustering strategy), which allows ERT users to improve the delimitation of the infiltration area in leachate injection monitoring. The MICS methodology is based on (i) a multiple inversion step by varying the inversion parameter values to take a wide range of resistivity models into account and (ii) a clustering strategy to improve the delineation of the infiltration front. In this paper, MICS was assessed on two types of data. First, a numerical assessment allows us to optimise and test MICS for different infiltration area sizes, contrasts and shapes. Second, MICS was applied to a field data set gathered during leachate recirculation on a bioreactor.

Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida.

PubMed

Dorey, L; Pelligand, L; Cheng, Z; Lees, P

2017-10-01

Pharmacokinetic-pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules of oxytetracycline for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in broth and porcine serum. PK/PD integration established ratios of average concentration over 48 h (C av0-48 h )/MIC of 5.87 and 0.27 μg/mL (P. multocida) and 0.70 and 0.85 μg/mL (A. pleuropneumoniae) for broth and serum MICs, respectively. PK/PD modelling of in vitro time-kill curves established broth and serum breakpoint values for area under curve (AUC 0-24 h )/MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4 log 10 reductions in bacterial count. Doses were then predicted for each pathogen, based on Monte Carlo simulations, for: (i) bacteriostatic and bactericidal levels of kill; (ii) 50% and 90% target attainment rates (TAR); and (iii) single dosing and daily dosing at steady-state. For 90% TAR, predicted daily doses at steady-state for bactericidal actions were 1123 mg/kg (P. multocida) and 43 mg/kg (A. pleuropneumoniae) based on serum MICs. Lower TARs were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg (P. multocida) and 34 mg/kg (A. pleuropneumoniae). © 2017 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms preexposed to subinhibitory concentrations of vancomycin.

PubMed

Doroshenko, Natalya; Tseng, Boo Shan; Howlin, Robert P; Deacon, Jill; Wharton, Julian A; Thurner, Philipp J; Gilmore, Brendan F; Parsek, Matthew R; Stoodley, Paul

2014-12-01

Staphylococcus epidermidis biofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure of S. epidermidis biofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treated S. epidermidis biofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added, S. epidermidis DNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellular d-Ala-d-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treated S. epidermidis biofilms, which might be an important factor for the persistence of biofilm infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Antianaerobic activity of sulopenem compared to six other agents.

PubMed

Ednie, Lois M; Appelbaum, Peter C

2009-05-01

Agar dilution MIC methodology was used to compare the activity of sulopenem with those of amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 431 anaerobes. Overall, MIC(50)/(90) values were as follows: sulopenem, 0.25/1.0 microg/ml; amoxicillin/clavulanate, 0.5/2.0 microg/ml; ampicillin/sulbactam, 0.5/4.0 microg/ml; piperacillin/tazobactam, 0.25/8.0 microg/ml; imipenem, 0.06/1.0 microg/ml; clindamycin, 0.25/16.0 microg/ml; and metronidazole, 1.0/4.0 microg/ml.

In Vivo Activities of Amoxicillin and Amoxicillin-Clavulanate against Streptococcus pneumoniae: Application to Breakpoint Determinations

PubMed Central

Andes, D.; Craig, W. A.

1998-01-01

The in vivo activities of amoxicillin and amoxicillin-clavulanate against 17 strains of Streptococcus pneumoniae with penicillin MICs of 0.12–8.0 mg/liter were assessed in a cyclophosphamide-induced neutropenic murine thigh infection model. Renal impairment was produced by administration of uranyl nitrate to prolong the amoxicillin half-life in the mice from 21 to 65 min, simulating human pharmacokinetics. Two hours after thigh infection with 105 to 106 CFU, groups of mice were treated with 7 mg of amoxicillin per kg of body weight alone or combined with clavulanate (ratio, 4:1) every 8 h for 1 and 4 days. There was an excellent correlation between the MIC of amoxicillin (0.03 to 5.6 mg/liter) and (i) the change in log10 CFU/thigh at 24 h and (ii) survival after 4 days of therapy. Organisms for which MICs were 2 mg/liter or less were killed at 1.4 to 4.2 and 1.6 to 4.1 log10 CFU/thigh at 24 h by amoxicillin and amoxicillin-clavulanate, respectively. The four strains for which MICs were >4 mg/liter grew 0.2 to 2.6 and 0.6 to 2.3 logs at 24 h despite therapy with amoxicillin and amoxicillin-clavulanate, respectively. Infection was uniformly fatal by 72 h in untreated mice. Amoxicillin therapy resulted in no mortality with organisms for which MICs were 1 mg/liter or less, 20 to 40% mortality with organisms for which MICs were 2 mg/liter, and 80 to 100% mortality with organisms for which MICs were 4.0–5.6 mg/liter. Lower and higher doses (0.5, 2, and 20 mg/kg) of amoxicillin were studied against organisms for which MICs were near the breakpoint. These studies demonstrate that a reduction of 1 log10 or greater in CFU/thigh at 24 h is consistently observed when amoxicillin levels exceed the MIC for 25 to 30% of the dosing interval. These studies would support amoxicillin (and amoxicillin-clavulanate) MIC breakpoints of 1 mg/liter for susceptible, 2 mg/liter for intermediate, and 4 mg/liter for resistant strains of S. pneumoniae. PMID:9736566

In Vitro Antimicrobial Activity and Effect on Biofilm Production of a White Grape Juice (Vitis vinifera) Extract.

PubMed

Filocamo, Angela; Bisignano, Carlo; Mandalari, Giuseppina; Navarra, Michele

2015-01-01

Background. The aim of the present study was to evaluate the antimicrobial effect of a white grape juice extract (WGJe) against a range of Gram-positive and Gram-negative bacteria, yeasts, and the fungus Aspergillus niger. WGJe was also tested on the production of bacterial biofilms in vitro. Results. WGJe inhibited in vitro most Gram-positive bacteria tested, Staphylococcus aureus ATCC 6538P being the most sensitive strain (MIC values of 3.9 μg/mL). The effect was bactericidal at the concentration of 500 μg/mL. Amongst the Gram-negative bacteria, Escherichia coli was the only susceptible strain (MIC and MBC of 2000 μg/mL). No effect on the growth of Candida sp. and the fungus Aspergillus niger was detected (MIC values > 2000 μg/mL). WGJe inhibited the biofilms formation of E. coli and Pseudomonas aeruginosa with a dose-dependent effect. Conclusions. WGJe exerted both bacteriostatic and bactericidal activity in vitro. The presented results could be used to develop novel strategies for the treatment of skin infections and against potential respiratory pathogens.

RX-P873, a Novel Protein Synthesis Inhibitor, Accumulates in Human THP-1 Monocytes and Is Active against Intracellular Infections by Gram-Positive (Staphylococcus aureus) and Gram-Negative (Pseudomonas aeruginosa) Bacteria

PubMed Central

Buyck, Julien M.; Peyrusson, Frédéric

2015-01-01

The pyrrolocytosine RX-P873, a new broad-spectrum antibiotic in preclinical development, inhibits protein synthesis at the translation step. The aims of this work were to study RX-P873's ability to accumulate in eukaryotic cells, together with its activity against extracellular and intracellular forms of infection by Staphylococcus aureus and Pseudomonas aeruginosa, using a pharmacodynamic approach allowing the determination of maximal relative efficacies (Emax values) and bacteriostatic concentrations (Cs values) on the basis of Hill equations of the concentration-response curves. RX-P873's apparent concentration in human THP-1 monocytes was about 6-fold higher than the extracellular one. In broth, MICs ranged from 0.125 to 0.5 mg/liter (S. aureus) and 2 to 8 mg/liter (P. aeruginosa), with no significant shift in these values against strains resistant to currently used antibiotics being noted. In concentration-dependent experiments, the pharmacodynamic profile of RX-P873 was not influenced by the resistance phenotype of the strains. Emax values (expressed as the decrease in the number of CFU from that in the initial inoculum) against S. aureus and P. aeruginosa reached more than 4 log units and 5 log units in broth, respectively, and 0.7 log unit and 2.7 log units in infected THP-1 cells, respectively, after 24 h. Cs values remained close to the MIC in all cases, making RX-P873 more potent than antibiotics to which the strains were resistant (moxifloxacin, vancomycin, and daptomycin for S. aureus; ciprofloxacin and ceftazidime for P. aeruginosa). Kill curves in broth showed that RX-P873 was more rapidly bactericidal against P. aeruginosa than against S. aureus. Taken together, these data suggest that RX-P873 may constitute a useful alternative for infections involving intracellular bacteria, especially Gram-negative species. PMID:26014952

Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

PubMed

Foster, D M; Sylvester, H J; Papich, M G

2017-12-01

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

Standardized comparison of antiseptic efficacy of triclosan, PVP-iodine, octenidine dihydrochloride, polyhexanide and chlorhexidine digluconate.

PubMed

Koburger, T; Hübner, N-O; Braun, M; Siebert, J; Kramer, A

2010-08-01

This study presents a comparative investigation of the antimicrobial efficacy of the antiseptics PVP-iodine, triclosan, chlorhexidine, octenidine and polyhexanide used for pre-surgical antisepsis and antiseptic treatment of skin, wounds and mucous membranes based on internationally accepted standards. MICs and MBCs were determined in accordance with DIN 58940-7 and 58940-8 using Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus), Enterococcus faecalis (including vancomycin-resistant Enterococcus), Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Clostridium perfringens, Haemophilus influenzae and Candida albicans. The microbicidal efficacy was determined in accordance with DIN EN 1040 and 1275 using S. aureus, P. aeruginosa and C. albicans. For chlorhexidine, octenidine and polyhexanide, MIC(48) and MBC(24) ranged from 16 to 32 mg/L. Maximum values for triclosan ranged from 256 to 512 mg/L, with an efficacy gap against P. aeruginosa, while the maximum values of PVP-iodine were 1024 mg/L, with a gap against S. pneumoniae. Comparing the minimal effective concentrations, octenidine was most effective. After 1 min, only octenidine and PVP-iodine fulfil the requirements for antiseptics. Tests under standardized and harmonized conditions help to choose the most efficacious agent. When a prolonged contact time is feasible, ranking of agents would be polyhexanide = octenidine > chlorhexidine > triclosan > PVP-iodine. This is consistent with the recommendations for antisepsis of acute wounds. Polyhexanide seems to be preferable for chronic wounds due to its higher tolerability. If an immediate effect is required, ranking would be octenidine = PVP-iodine> polyhexanide > chlorhexidine > triclosan.

Antimicrobial Susceptibility to Azithromycin among Salmonella enterica Isolates from the United States▿

PubMed Central

Sjölund-Karlsson, Maria; Joyce, Kevin; Blickenstaff, Karen; Ball, Takiyah; Haro, Jovita; Medalla, Felicita M.; Fedorka-Cray, Paula; Zhao, Shaohua; Crump, John A.; Whichard, Jean M.

2011-01-01

Due to emerging resistance to traditional antimicrobial agents, such as ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from humans, food animals, and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy-two Salmonella enterica serotype Typhi isolates from humans were also tested. For each isolate, MICs of azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonella isolates, azithromycin MICs among human isolates ranged from 1 to 32 μg/ml, whereas the MICs among the animal and retail meat isolates ranged from 2 to 16 μg/ml and 4 to 16 μg/ml, respectively. Among Salmonella serotype Typhi isolates, the azithromycin MICs ranged from 4 to 16 μg/ml. The highest MIC observed in the present study was 32 μg/ml, and it was detected in three human isolates belonging to serotypes Kentucky, Montevideo, and Paratyphi A. Based on our findings, we propose an epidemiological cutoff value (ECOFF) for wild-type Salmonella of ≤16 μg/ml of azithromycin. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica. PMID:21690279

Antimicrobial Susceptibility Patterns of Enterococcus faecalis and Enterococcus faecium Isolated from Poultry Flocks in Germany.

PubMed

Maasjost, J; Mühldorfer, K; Cortez de Jäckel S; Hafez, H M

2015-03-01

Between 2010 and 2011, 145 Enterococcus isolates (Enterococcus faecalis, n = 127; Enterococcus faecium, n = 18) were collected during routine bacteriologic diagnostics from broilers, layers, and fattening turkeys in Germany showing various clinical signs. The susceptibility to 24 antimicrobial agents was investigated by broth microdilution test to determine minimum inhibitory concentrations (MICs). All E. faecalis isolates (n = 127) were susceptible to the beta-lactam antibiotics ampicillin, amoxicillin-clavulanic acid, and penicillin. Corresponding MIC with 50% inhibition (MIC50) and MIC with 90% inhibition (MIC90) values of these antimicrobial agents were at the lower end of the test range (≤ 4 μg/ml). In addition, no vancomycin-resistant enterococci (VRE) were found. High resistance rates were identified in both Enterococcus species for lincomycin (72%-99%) and tetracycline (67%-82%). Half or more than half of Enterococcus isolates were resistant to gentamicin (54%-72%) and the macrolide antibiotics erythromycin (44%-61%) and tylosin-tartate (44%-56%). Enterococcus faecalis isolated from fattening turkeys showed the highest prevalence of antimicrobial resistance compared to other poultry production systems. Eighty-nine out of 145 Enterococcus isolates were resistant to three or more antimicrobial classes. Again, turkeys stood out with 42 (8 1%) multiresistant isolates. The most-frequent resistance patterns of E. faecalis were gentamicin, lincomycin, and tetracycline in all poultry production systems.

Synthesis and quantitative structure activity relationship (QSAR) of arylidene (benzimidazol-1-yl)acetohydrazones as potential antibacterial agents.

PubMed

El-Kilany, Yeldez; Nahas, Nariman M; Al-Ghamdi, Mariam A; Badawy, Mohamed E I; El Ashry, El Sayed H

2015-01-01

Ethyl (benzimidazol-1-yl)acetate was subjected to hydrazinolysis with hydrazine hydrate to give (benzimidazol-1-yl)acetohydrazide. The latter was reacted with various aromatic aldehydes to give the respective arylidene (1H-benzimidazol-1-yl)acetohydrazones. Solutions of the prepared hydrazones were found to contain two geometric isomers. Similarly (2-methyl-benzimidazol-1-yl)acetohydrazide was reacted with various aldehydes to give the corresponding hydrazones. The antibacterial activity was evaluated in vitro by minimum inhibitory concentration (MIC) against Agrobacterium tumefaciens (A. tumefaciens), Erwinia carotovora (E. carotovora), Corynebacterium fascians (C. fascians) and Pseudomonas solanacearum (P. solanacearum). MIC result demonstrated that salicylaldehyde(1H-benzimidazol-1-yl)acetohydrazone (4) was the most active compound (MIC = 20, 35, 25 and 30 mg/L against A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively). Quantitative structure activity relationship (QSAR) investigation using Hansch analysis was applied to find out the correlation between antibacterial activity and physicochemical properties. Various physicochemical descriptors and experimentally determined MIC values for different microorganisms were used as independent and dependent variables, respectively. pMICs of the compounds exhibited good correlation (r = 0.983, 0.914, 0.960 and 0.958 for A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively) with the prediction made by the model. QSAR study revealed that the hydrophobic parameter (ClogP), the aqueous solubility (LogS), calculated molar refractivity, topological polar surface area and hydrogen bond acceptor were found to have overall significant correlation with antibacterial activity. The statistical results of training set, correlation coefficient (r and r (2)), the ratio between regression and residual variances (f, Fisher's statistic), the standard error of estimates and significant (s) gave reliability to the prediction of molecules with activity using QSAR models. However, QSAR equations derived for the MIC values against the tested bacteria showed negative contribution of molecular mass.

Development of an Antimicrobial Susceptibility Testing Method Suitable for Performing During Space Flight

NASA Technical Reports Server (NTRS)

Jorgensen, James H.; Skweres, Joyce A.; Mishra S. K.; McElmeel, M. Letticia; Maher, Louise A.; Mulder, Ross; Lancaster, Michael V.; Pierson, Duane L.

1997-01-01

Very little is known regarding the affects of the microgravity environment of space flight upon the action of antimicrobial agents on bacterial pathogens. This study was undertaken to develop a simple method for conducting antibacterial susceptibility tests during a Space Shuttle mission. Specially prepared susceptibility test research cards (bioMerieux Vitek, Hazelwood, MO) were designed to include 6-11 serial two-fold dilutions of 14 antimicrobial agents, including penicillins, cephalosporins, a Beta-lactamase inhibitor, vancomycin, erythromycin, tetracycline, gentamicin, ciprofloxacin, and trimethoprim/sulfamethoxazole. Minimal inhibitory concentrations (MICS) of the drugs were determined by visual reading of color endpoints in the Vitek research cards made possible by incorporation of a colorimetric growth indicator (alamarBlue(Trademark), Accumed International, Westlake, OH). This study has demonstrated reproducible susceptibility results when testing isolates of Staphylococcus aurezis, Group A Streptococcus, Enterococcusfaecalis, Escherichia coli (beta-lactamase positive and negative strains), Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomoiias aeruginosa. In some instances, the MICs were comparable to those determined using a standard broth microdilution method, while in some cases the unique test media and format yielded slightly different values, that were themselves reproducible. The proposed in-flight experiment will include inoculation of the Vitek cards on the ground prior to launch of the Space Shuttle, storage of inoculated cards at refrigeration temperature aboard the Space Shuttle until experiment initiation, then incubation of the cards for 18-48 h prior to visual interpretation of MICs by the mission's astronauts. Ground-based studies have shown reproducible MICs following storage of inoculated cards for 7 days at 4-8 C to accommodate the mission's time schedule and the astronauts' activities. For comparison, ground-based control (normal gravity) MIC values will be generated by simultaneous inoculation and incubation of a second set of test cards in a laboratory at the launch site. This procedure can provide a safe and compact experiment that should yield new information on the affects of microgravity on the biological activities of various classes of antibiotics.

In Vivo Pharmacodynamic Target Assessment of Eravacycline against Escherichia coli in a Murine Thigh Infection Model.

PubMed

Zhao, Miao; Lepak, Alexander J; Marchillo, Karen; VanHecker, Jamie; Andes, David R

2017-07-01

Eravacycline is a novel fluorocycline antibiotic with potent activity against a broad range of pathogens, including strains with tetracycline and other drug resistance phenotypes. The goal of the studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated with efficacy in the murine thigh infection model. Six Escherichia coli isolates were utilized for the studies. MICs were determined using CLSI methods and ranged from 0.125 to 0.25 mg/liter. A neutropenic murine thigh infection model was utilized for all treatment studies. Single-dose plasma pharmacokinetics were determined in mice after administration of 2.5, 5, 10, 20, 40, and 80 mg/kg of body weight. Pharmacokinetic studies exhibited maximum plasma concentration ( C max ) values of 0.34 to 2.58 mg/liter, area under the concentration-time curve (AUC) from time zero to infinity (AUC 0-∞ ) values of 2.44 to 57.6 mg · h/liter, and elimination half-lives of 3.9 to 17.6 h. Dose fractionation studies were performed using total drug doses of 6.25 mg/kg to 100 mg/kg fractionated into 6-, 8-, 12-, or 24-h regimens. Nonlinear regression analysis demonstrated that the 24-h free drug AUC/MIC ( f AUC/MIC) was the PK/PD parameter that best correlated with efficacy ( R 2 = 0.80). In subsequent studies, we used the neutropenic murine thigh infection model to determine if the magnitude of the AUC/MIC needed for the efficacy of eravacycline varied among pathogens. Mice were treated with 2-fold increasing doses (range, 3.125 to 50 mg/kg) of eravacycline every 12 h. The mean f AUC/MIC magnitudes associated with the net stasis and the 1-log-kill endpoints were 27.97 ± 8.29 and 32.60 ± 10.85, respectively. Copyright © 2017 American Society for Microbiology.

In vitro Antibacterial Activity of Ocimum suave Essential Oils against Uropathogens Isolated from Patients in Selected Hospitals in Bushenyi District, Uganda

PubMed Central

Tibyangye, Julius; Okech, Matilda Angela; Nyabayo, Josephat Maniga; Nakavuma, Jessica Lukanga

2015-01-01

Aims To determine antibacterial activity of Ocimum suave essential oils against bacterial uropathogens. Study Design A cross sectional and experimental study. Place and Duration of Study Six selected hospitals in Bushenyi District, Uganda between June 2012 and July 2013. Methodology Clean catch midstream urine samples were collected and inoculated on Cystine Lysine Electrolyte Deficient (CLED) agar. The plates were incubated at 37°C for 24hrs to 48hrs. The O. suave essential oils were extracted by hydrodistillation of leaves for 4hrs using a Clevenger apparatus. The oil was collected and dried over anhydrous sodium sulphate (Na2SO4) and kept at 4°C till further use. The antimicrobial activity of O. suave essential oils against isolates was determined by agar well method. The MIC of O. suave essential oil extract was carried out by microbroth dilution method. Results Of the three hundred (300) midstream urine samples collected, 67(22.33%) had significant bacterial growth. Escherichia coli is the most common isolate (61.19%, n = 41). The essential oil from O. suave showed activity against isolates of E. coli, K. pneumoniae, S. aureus, E. feacalis, M. morganii, Citrobacter species, Enterobacter species and P. aeruginosa with mean zone of inhibition (ZI) ranging from 10–22 mm. The essential oils had no inhibitory activity on Acinetobacter species. The minimum inhibitory concentration (MIC) for O. suave essential oils ranged from 0.78 to 22 μg/ml. This study showed that O. suave essential oils had MIC value of 0.78 μg/ml against S. aureus and MIC values ranging from 3 to 22 μg/ml against the other tested isolates. Conclusion The most common uropathogen was E. coli (61.19% n = 41). O. suave essential oils exhibited antibacterial activity against majority of the uropathogens, except Acinetobacter species, mean ZI of 10–22 mm and MIC of 0.78 – 22 μg/ml. PMID:26120574

In Vitro Antibacterial Activities of JNJ-Q2, a New Broad-Spectrum Fluoroquinolone ▿ ‡

PubMed Central

Morrow, Brian J.; He, Wenping; Amsler, Karen M.; Foleno, Barbara D.; Macielag, Mark J.; Lynch, A. Simon; Bush, Karen

2010-01-01

JNJ-Q2, a novel fluorinated 4-quinolone, was evaluated for its antibacterial potency by broth and agar microdilution MIC methods in studies focused on skin and respiratory tract pathogens, including strains exhibiting contemporary fluoroquinolone resistance phenotypes. Against a set of 118 recent clinical isolates of Streptococcus pneumoniae, including fluoroquinolone-resistant variants bearing multiple DNA topoisomerase target mutations, an MIC90 value for JNJ-Q2 of 0.12 μg/ml was determined, indicating that it was 32-fold more potent than moxifloxacin. Against a collection of 345 recently collected methicillin-resistant Staphylococcus aureus (MRSA) isolates, including 256 ciprofloxacin-resistant strains, the JNJ-Q2 MIC90 value was 0.25 μg/ml, similarly indicating that it was 32-fold more potent than moxifloxacin. The activities of JNJ-Q2 against Gram-negative pathogens were generally comparable to those of moxifloxacin. In further studies, JNJ-Q2 exhibited bactericidal activities at 2× and 4× MIC levels against clinical isolates of S. pneumoniae and MRSA with various fluoroquinolone susceptibilities, and its activities were enhanced over those of moxifloxacin. In these studies, the activity exhibited against strains bearing gyrA, parC, or gyrA plus parC mutations was indicative of the relatively balanced (equipotent) activity of JNJ-Q2 against the DNA topoisomerase target enzymes. Finally, determination of the relative rates or frequencies of the spontaneous development of resistance to JNJ-Q2 at 2× and 4× MICs in S. pneumoniae, MRSA, and Escherichia coli were indicative of a lower potential for resistance development than that for current fluoroquinolones. In conclusion, JNJ-Q2 exhibits a range of antibacterial activities in vitro that is supportive of its further evaluation as a potential new agent for the treatment of skin and respiratory tract infections. PMID:20176911

Prevalence, genetic relatedness and antibiotic resistance of hospital-acquired clostridium difficile PCR ribotype 018 strains.

PubMed

Seo, Mi-Ran; Kim, Jieun; Lee, Yangsoon; Lim, Dong-Gyun; Pai, Hyunjoo

2018-05-01

Clostridium difficile infection (CDI) is a major healthcare-associated infection. The aim of this study was to investigate the genetic relatedness of the endemic C. difficile PCR ribotype 018 strains in an institution and changes to their characteristics during a five-year period. A total of 207 isolates from inpatients at Hanyang University Hospital from 2009 to 2013 were analysed using multilocus variable-number tandem-repeat analysis (MLVA). Minimum inhibitory concentrations (MICs) of several antibiotics were determined. In total, 204 (98.6%) were genetically related, with a summed tandem-repeat distance (STRD) ≤ 10. Minimum-spanning-tree analysis identified 78 MLVA types, categorized into six clonal complexes (CCs). The largest cluster, CC-I, included 51 MLVA types from 148 isolates (71.5%) and the second largest cluster, CC-II, included 10 MLVA types from 36 isolates (17.4%). Resistance rates for antibiotics were: clindamycin (CLI), 97.6%; moxifloxacin (MXF), 98.6%; vancomycin (VAN), 1.4%; and rifaximin (RFX), 8.2%. All isolates were susceptible to piperacillin/tazobactam (TZP) and metronidazole (MTZ). Comparing the MICs of antibiotics for the isolates each year from 2009 to 2013, MICs of antibiotics that promote CDI, such as CLI, MXF, TZP and RFX, increased over the five-year period (P-value by Kruskal-Wallis test: < 0.0001, <0.0001, <0.0001, and <0.0001 respectively); however, MICs of VAN or MTZ, antibiotics for treatment of CDI, did not increase or decreased over the same time period (P-value by Kruskal-Wallis test: 0.166, <0.0001). C. difficile RT018 isolates in a tertiary hospital over a five-year period presented a close clonal relationship. MICs of antibiotics promoting CDI increased with this clonal expansion. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Antifungal compounds from Zanthoxylum chiloperone var. angustifolium.

PubMed

Thouvenel, Céline; Gantier, Jean-Charles; Duret, Philippe; Fourneau, Christophe; Hocquemiller, Reynald; Ferreira, Maria-Elena; Rojas de Arias, Antonieta; Fournet, Alain

2003-06-01

An alkaloidal extract of the stem barks of Zanthoxylum chiloperone var. angustifolium exhibited antifungal activity against Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes var. interdigitale using a TLC bioautographic method. Bioassay-guided fractionation of this extract resulted in the isolation of two active compounds identi fi ed as canthin-6-one and 5-methoxycanthin-6-one. Canthin-6-one exhibited a broad spectrum of activities against Aspergillus fumigatus, A. niger, A. terreus, Candida albicans, C. tropicalis, C. glabrata, Cryptococcus neoformans, Geotrichum candidum, Saccharomyces cerevisiae, Trichosporon beigelii, Trichosporon cutaneum and Trichophyton mentagrophytes var. interdigitale with MICs values between 5.3 and 46 micro mol/L. 5-methoxy-canthin-6-one was active against only Trichophyton mentagrophytes var. interdigitale with a MIC value of 12.3 micro mol/L. Copyright 2003 John Wiley & Sons, Ltd.

Statistics for stochastic modeling of volume reduction, hydrograph extension, and water-quality treatment by structural stormwater runoff best management practices (BMPs)

USGS Publications Warehouse

Granato, Gregory E.

2014-01-01

The U.S. Geological Survey (USGS) developed the Stochastic Empirical Loading and Dilution Model (SELDM) in cooperation with the Federal Highway Administration (FHWA) to indicate the risk for stormwater concentrations, flows, and loads to be above user-selected water-quality goals and the potential effectiveness of mitigation measures to reduce such risks. SELDM models the potential effect of mitigation measures by using Monte Carlo methods with statistics that approximate the net effects of structural and nonstructural best management practices (BMPs). In this report, structural BMPs are defined as the components of the drainage pathway between the source of runoff and a stormwater discharge location that affect the volume, timing, or quality of runoff. SELDM uses a simple stochastic statistical model of BMP performance to develop planning-level estimates of runoff-event characteristics. This statistical approach can be used to represent a single BMP or an assemblage of BMPs. The SELDM BMP-treatment module has provisions for stochastic modeling of three stormwater treatments: volume reduction, hydrograph extension, and water-quality treatment. In SELDM, these three treatment variables are modeled by using the trapezoidal distribution and the rank correlation with the associated highway-runoff variables. This report describes methods for calculating the trapezoidal-distribution statistics and rank correlation coefficients for stochastic modeling of volume reduction, hydrograph extension, and water-quality treatment by structural stormwater BMPs and provides the calculated values for these variables. This report also provides robust methods for estimating the minimum irreducible concentration (MIC), which is the lowest expected effluent concentration from a particular BMP site or a class of BMPs. These statistics are different from the statistics commonly used to characterize or compare BMPs. They are designed to provide a stochastic transfer function to approximate the quantity, duration, and quality of BMP effluent given the associated inflow values for a population of storm events. A database application and several spreadsheet tools are included in the digital media accompanying this report for further documentation of methods and for future use. In this study, analyses were done with data extracted from a modified copy of the January 2012 version of International Stormwater Best Management Practices Database, designated herein as the January 2012a version. Statistics for volume reduction, hydrograph extension, and water-quality treatment were developed with selected data. Sufficient data were available to estimate statistics for 5 to 10 BMP categories by using data from 40 to more than 165 monitoring sites. Water-quality treatment statistics were developed for 13 runoff-quality constituents commonly measured in highway and urban runoff studies including turbidity, sediment and solids; nutrients; total metals; organic carbon; and fecal coliforms. The medians of the best-fit statistics for each category were selected to construct generalized cumulative distribution functions for the three treatment variables. For volume reduction and hydrograph extension, interpretation of available data indicates that selection of a Spearman’s rho value that is the average of the median and maximum values for the BMP category may help generate realistic simulation results in SELDM. The median rho value may be selected to help generate realistic simulation results for water-quality treatment variables. MIC statistics were developed for 12 runoff-quality constituents commonly measured in highway and urban runoff studies by using data from 11 BMP categories and more than 167 monitoring sites. Four statistical techniques were applied for estimating MIC values with monitoring data from each site. These techniques produce a range of lower-bound estimates for each site. Four MIC estimators are proposed as alternatives for selecting a value from among the estimates from multiple sites. Correlation analysis indicates that the MIC estimates from multiple sites were weakly correlated with the geometric mean of inflow values, which indicates that there may be a qualitative or semiquantitative link between the inflow quality and the MIC. Correlations probably are weak because the MIC is influenced by the inflow water quality and the capability of each individual BMP site to reduce inflow concentrations.

Nonaqueous Hybrid Lithium-Ion and Sodium-Ion Capacitors.

PubMed

Wang, Huanwen; Zhu, Changrong; Chao, Dongliang; Yan, Qingyu; Fan, Hong Jin

2017-12-01

Hybrid metal-ion capacitors (MICs) (M stands for Li or Na) are designed to deliver high energy density, rapid energy delivery, and long lifespan. The devices are composed of a battery anode and a supercapacitor cathode, and thus become a tradeoff between batteries and supercapacitors. In the past two decades, tremendous efforts have been put into the search for suitable electrode materials to overcome the kinetic imbalance between the battery-type anode and the capacitor-type cathode. Recently, some transition-metal compounds have been found to show pseudocapacitive characteristics in a nonaqueous electrolyte, which makes them interesting high-rate candidates for hybrid MIC anodes. Here, the material design strategies in Li-ion and Na-ion capacitors are summarized, with a focus on pseudocapacitive oxide anodes (Nb 2 O 5 , MoO 3 , etc.), which provide a new opportunity to obtain a higher power density of the hybrid devices. The application of Mxene as an anode material of MICs is also discussed. A perspective to the future research of MICs toward practical applications is proposed to close. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chiral lactic hydrazone derivatives as potential bioactive antibacterial agents: Synthesis, spectroscopic, structural and molecular docking studies

NASA Astrophysics Data System (ADS)

Noshiranzadeh, Nader; Heidari, Azam; Haghi, Fakhri; Bikas, Rahman; Lis, Tadeusz

2017-01-01

A series of novel chiral lactic-hydrazone derivatives were synthesized by condensation of (S)-lactic acid hydrazide with salicylaldehyde derivatives and characterized by elemental analysis and spectroscopic studies (FT-IR, 1H NMR and 13C NMR spectroscopy). The structure of one compound was determined by single crystal X-ray analysis. Antibacterial activity of the synthesized compounds was studied against Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli and Pseudomonas aeruginosa as bacterial cultures by broth microdilution method. All of the synthesized compounds showed good antibacterial activity with MIC range of 64-512 μg/mL. Compounds (S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene)propanehydrazide (5) and (S,E)-2-hydroxy-N-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)propanehydrazide (7) were the most effective antibacterial derivatives against S. aureus and E. coli respectively with a MIC value of 64 μg/mL. Bacterial biofilm formation assay showed that these compounds significantly inhibited biofilm formation of P. aeruginosa. Also, in silico molecular docking studies were performed to show lipoteichoic acid synthase (LtaS) inhibitory effect of lactic hydrazone derivatives. The association between electronic and structural effects of some substituents on the benzylidene moiety and the biological activity of these chiral compounds were studied. Structural studies show that compound with higher hydrogen bonding interactions show higher antibacterial activity. The results show chiral hydrazone derivatives based on lactic acid hydrazide could be used as potential lead compounds for developing novel antibacterial agents.

EFFECTS OF DIFFERENT HYDROPONIC SUBSTRATE COMBINATIONS AND WATERING REGIMES ON PHYSIOLOGICAL AND ANTI-FUNGAL PROPERTIES OF SIPHONOCHILUS AETHIOPICUS

PubMed Central

S, Xego; L, Kambizi; F, Nchu

2017-01-01

Background: Production of medicinal plants in controlled environments, particularly hydroponic technology, provides opportunities for high quality biomass accumulation and optimizes production of secondary metabolites. Applying special watering regimes in combination with efficient soil draining is an encouraging new tool for the production of pharmaceutical relevant plants. The purpose of this paper was to evaluate the effect of substrate combinations and watering regimes on nutrient uptake, anti-F. oxysporum activity and secondary metabolite profile of S. aethiopicus. Materials and Methods: Coir was used as the main component for the preparation of media in different combinations; TI (Coir + vermiculite + perlite + bark), T2 (Coir + bark), T3 (Coir + perlite) and T4 (Coir + vermiculite). Plants in different treatments were grown under two watering regimes: 3 and 5-days watering intervals. At 9 weeks post treatment, plants were harvested, oven dried and tissue nutrient content, anti-F. oxysporum activity and secondary metabolites were analyzed. Results: The results showed that there were significant differences (P < 0.05) on the uptake of P, K, N, Mg, Fe, Cu, B and NH4-.The highest mean values for most nutrients were obtained in treatments under 3-days interval. Acetone extracts of S. aethiopicus under 5-days interval were the most bioactive against F. oxysporum. The MIC values obtained are relatively lower for the rhizomes, ranging from 0.078 - 0.3125 mg/ml compared to the higher MIC values (0.375 - 0.75 mg/ml) obtained in the leaves. LC-MS analysis of acetone extracts revealed the presence of phytochemicals such as caffeic acid, quercetin, p-hydroxybenzoic acid, rutin, kaempferol, epicatechin, naringenin, hesperetin and protocatechuic acid. Conclusion: The antimicrobial activity and/or the phytochemical profile of the crude extracts were affected by watering regimes. PMID:28480420

EFFECTS OF DIFFERENT HYDROPONIC SUBSTRATE COMBINATIONS AND WATERING REGIMES ON PHYSIOLOGICAL AND ANTI-FUNGAL PROPERTIES OF SIPHONOCHILUS AETHIOPICUS.

PubMed

S, Xego; L, Kambizi; F, Nchu

2017-01-01

Production of medicinal plants in controlled environments, particularly hydroponic technology, provides opportunities for high quality biomass accumulation and optimizes production of secondary metabolites. Applying special watering regimes in combination with efficient soil draining is an encouraging new tool for the production of pharmaceutical relevant plants. The purpose of this paper was to evaluate the effect of substrate combinations and watering regimes on nutrient uptake, anti- F. oxysporum activity and secondary metabolite profile of S. aethiopicus . Coir was used as the main component for the preparation of media in different combinations; TI (Coir + vermiculite + perlite + bark), T2 (Coir + bark), T3 (Coir + perlite) and T4 (Coir + vermiculite). Plants in different treatments were grown under two watering regimes: 3 and 5-days watering intervals. At 9 weeks post treatment, plants were harvested, oven dried and tissue nutrient content, anti- F. oxysporum activity and secondary metabolites were analyzed. The results showed that there were significant differences ( P < 0.05) on the uptake of P, K, N, Mg, Fe, Cu, B and NH4 - .The highest mean values for most nutrients were obtained in treatments under 3-days interval. Acetone extracts of S. aethiopicus under 5-days interval were the most bioactive against F. oxysporum . The MIC values obtained are relatively lower for the rhizomes, ranging from 0.078 - 0.3125 mg/ml compared to the higher MIC values (0.375 - 0.75 mg/ml) obtained in the leaves. LC-MS analysis of acetone extracts revealed the presence of phytochemicals such as caffeic acid, quercetin, p-hydroxybenzoic acid, rutin, kaempferol, epicatechin, naringenin, hesperetin and protocatechuic acid. The antimicrobial activity and/or the phytochemical profile of the crude extracts were affected by watering regimes.

Phytochemical, antimicrobial, and antioxidant activities of different citrus juice concentrates.

PubMed

Oikeh, Ehigbai I; Omoregie, Ehimwenma S; Oviasogie, Faith E; Oriakhi, Kelly

2016-01-01

The search for new antimicrobial compounds is ongoing. Its importance cannot be overemphasized in an era of emerging resistant pathogenic organisms. This study therefore investigated the phytochemical composition and antioxidant and antimicrobial activities of different citrus juice concentrates. Fruit juices of Citrus tangerine (tangerine), Citrus paradisi (grape), Citrus limon (lemon), and Citrus aurantifolia (lime) were evaluated. Antimicrobial activities against five bacterial and three fungal strains were evaluated. The results revealed the presence of alkaloids, flavonoids, steroids, terpenoids, saponins, cardiac glycosides, and reducing sugars in all the juice concentrates. DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging capacities varied with tangerine and grape juices having better scavenging capacities than lemon and lime juices. Grape juice was observed to have a significantly higher (P < 0.05) ferric-reducing antioxidant potential (FRAP) value (364.2 ± 10.25 μmol/L Fe(II)/g of the extract) than the reference antioxidant, ascorbic acid (312.88 ± 5.61 μmol/L). Antimicrobial studies revealed differential antimicrobial activities against different microbial strains. Zones of inhibition ranging from 4 to 26 mm were observed for the antibacterial tests with 0-24 mm for antifungal test. Minimum inhibitory concentrations (MIC) and minimum bacteriostatic concentrations (MBC) for concentrates against bacterial strains ranged from 12.5 to 200 μg/mL. Lemon and lime juice concentrates had lower MIC and MBC values with orange and tangerine having the highest values. Minimum fungicidal concentrations ranged from 50 to 200 μg/mL. The results of this study suggest that these juice concentrates may have beneficial antimicrobial roles that can be exploited in controlling unwanted microbial growth.

Antibacterial and antibiotic potentiating activities of tropical marine sponge extracts.

PubMed

Beesoo, Rima; Bhagooli, Ranjeet; Neergheen-Bhujun, Vidushi S; Li, Wen-Wu; Kagansky, Alexander; Bahorun, Theeshan

2017-06-01

Increasing prevalence of antibiotic resistance has led research to focus on discovering new antimicrobial agents derived from the marine biome. Although ample studies have investigated sponges for their bioactive metabolites with promising prospects in drug discovery, the potentiating effects of sponge extracts on antibiotics still remains to be expounded. The present study aimed to investigate the antibacterial capacity of seven tropical sponges collected from Mauritian waters and their modulatory effect in association with three conventional antibiotics namely chloramphenicol, ampicillin and tetracycline. Disc diffusion assay was used to determine the inhibition zone diameter (IZD) of the sponge total crude extracts (CE), hexane (HF), ethyl acetate (EAF) and aqueous (AF) fractions against nine standard bacterial isolates whereas broth microdilution method was used to determine their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and antibiotic potentiating activity of the most active sponge extract. MIC values of the sponge extracts ranged from 0.039 to 1.25mg/mL. Extracts from Neopetrosia exigua rich in beta-sitosterol and cholesterol displayed the widest activity spectrum against the 9 tested bacterial isolates whilst the best antibacterial profile was observed by its EAF particularly against Staphylococcus aureus and Bacillus cereus with MIC and MBC values of 0.039mg/mL and 0.078mg/mL, respectively. The greatest antibiotic potentiating effect was obtained with the EAF of N. exigua (MIC/2) and ampicillin combination against S. aureus. These findings suggest that the antibacterial properties of the tested marine sponge extracts may provide an alternative and complementary strategy to manage bacterial infections. Copyright © 2017 Elsevier Inc. All rights reserved.

Simulated comparison of the pharmacodynamics of ciprofloxacin and levofloxacin against Pseudomonas aeruginosa using pharmacokinetic data from healthy volunteers and 2002 minimum inhibitory concentration data.

PubMed

Burgess, David S; Hall, Ronald G

2007-07-01

Until the 2002 approval of levofloxacin 750 mg QD, ciprofloxacin was the fluoroquinolone of choice against Pseudomonas aeruginosa infections. This study evaluated the AUC:MIC ratios for ciprofloxacin 400 mg BID and TID and levofloxacin 750 mg QD, all administered intravenously, against P. aeruginosa using a Monte Carlo simulation. Pharmacokinetic data for ciprofloxacin and levofloxacin and 2002 MIC distributions against P. aeruginosa were obtained from studies in healthy volunteers published in the peer-reviewed literature. Pharmacokinetic studies of each agent were identified by separate MEDLINE searches combining the MeSH heading pharmacokinetics with the generic name of the antimicrobial. Only human studies published in English between 1990 and 2001 were included. Included studies also had to meet 3 minimum criteria: evaluation of clinically relevant dosing regimens, use of rigorous study methods, and provision of mean (SD) values for the pharmacokinetic parameters of interest. When multiple studies met these criteria, a single study was selected for each antimicrobial regimen. Pharmacodynamic analysis was performed using a Monte Carlo simulation of 10,000 patients by integrating the pharmacokinetic parameters, their variability, and 2002 MIC distributions for each antimicrobial regimen. The probability of target attainment was determined for each regimen for an AUC:MIC ratio from 0 to 300. A > or =90% probability of target attainment was considered satisfactory. For ciprofloxacin 400 mg TID and levofloxacin 750 mg QD, the AUC:MIC ratio at the corresponding 2002 Clinical Laboratory Standards Institute break points of 1 and 2 microg/mL were 33 and 34, respectively. The probabilities of target attainment for a free AUC:MIC ratio >90 (equivalent to a total AUC:MIC ratio > or =125) were 47% for ciprofloxacin 400 mg BID, 54% for ciprofloxacin 400 mg TID, and 48% for levofloxacin 750 mg QD. When pharmacokinetic data from healthy volunteers and 2002 MIC data were used, none of the simulated fluoroquinolone regimens achieved a high likelihood of target attainment against P. aeruginosa.

Ceftaroline efficacy against high-MIC clinical Staphylococcus aureus isolates in an in vitro hollow-fibre infection model.

PubMed

Singh, Renu; Almutairi, Mashal; Alm, Richard A; Lahiri, Sushmita D; San Martin, Maryann; Chen, April; Ambler, Jane E

2017-10-01

The current CLSI and EUCAST clinical susceptible breakpoint for 600 mg q12h dosing of ceftaroline (active metabolite of ceftaroline fosamil) for Staphylococcus aureus is ≤1 mg/L. Efficacy data for S. aureus infections with ceftaroline MIC ≥2 mg/L are limited. This study was designed to generate in-depth pharmacokinetic/pharmacodynamics (PK/PD) understanding of S. aureus isolates inhibited by ≥ 2 mg/L ceftaroline using an in vitro hollow-fibre infection model (HFIM). The PK/PD target of ceftaroline was investigated against 12 diverse characterized clinical MRSA isolates with ceftaroline MICs of 2 or 4 mg/L using q8h dosing for 24 h. These isolates carried substitutions in the penicillin-binding domain (PBD) and/or the non-PBD. Additionally, PD responses of mutants with ceftaroline MICs ranging from 2 to 32 mg/L were evaluated against the mean 600 mg q8h human-simulated dose over 72 h. The mean stasis, 1 log10-kill and 2 log10-kill PK/PD targets were 29%, 32% and 35% f T>MIC, respectively. In addition, these data suggest that the PK/PD target for MRSA is not impacted by the presence of substitutions in the non-PBD commonly found in isolates with ceftaroline MIC values of ≤ 2 mg/L. HFIM studies with 600 mg q8h dosing demonstrated a sustained long-term bacterial suppression for isolates with ceftaroline MICs of 2 and 4 mg/L. Overall, efficacy was demonstrated against a diverse collection of clinical isolates using HFIM indicating the utility of 600 mg ceftaroline fosamil for S. aureus isolates with MIC ≤4 mg/L using q8h dosing. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies.

PubMed

La Regina, Giuseppe; D'Auria, Felicia Diodata; Tafi, Andrea; Piscitelli, Francesco; Olla, Stefania; Caporuscio, Fabiana; Nencioni, Lucia; Cirilli, Roberto; La Torre, Francesco; De Melo, Nadja Rodrigues; Kelly, Steven L; Lamb, David C; Artico, Marino; Botta, Maurizio; Palamara, Anna Teresa; Silvestri, Romano

2008-07-10

New 1-[(3-aryloxy-3-aryl)propyl]-1 H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure-activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketoconazole, miconazole, and econazole, and were more potent than fluconazole. Several derivatives ( 10, 12, 14, 18- 20, 24, 28, 29, 30, and 34) turned out to be potent inhibitors of C. albicans strains resistant to fluconazole, with MIC values less than 10 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC

In Vitro Antimicrobial and Modulatory Activity of the Natural Products Silymarin and Silibinin

PubMed Central

Rakelly de Oliveira, Dayanne; Relison Tintino, Saulo; Morais Braga, Maria Flaviana Bezerra; Boligon, Aline Augusti; Linde Athayde, Margareth; Douglas Melo Coutinho, Henrique; de Menezes, Irwin Rose Alencar; Fachinetto, Roselei

2015-01-01

Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line. PMID:25866771

Evaluation of Antimicrobial Activity of the Methanol Extracts from 8 Traditional Medicinal Plants

PubMed Central

Kang, Chang-Geun; Hah, Dae-Sik; Kim, Chung-Hui; Kim, Young-Hwan; Kim, Euikyung

2011-01-01

The methanol extract of 12 medicinal plants were evaluated for its antibacterial activity against Gram-positive (5 strains) and Gram-negative bacteria (10 strains) by assay for minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) . The antibacterial activity was determined by an agar dilution method (according to the guidelines of Clinical and Laboratory Standard Institute) . All the compounds (12 extracts) of the 8 medicinal plants (leaf or root) were active against both Gram-negative and Gram-positive bacteria. Gram-negative showed a more potent action than Gram positive bacteria. The MIC concentrations were various ranged from 0.6 μg/ml to 5000 μg/ml. The lowest MIC (0.6 μg/ml) and MBC (1.22 μg/ml) values were obtained with extract on 4 and 3 of the 15 microorganisms tested, respectively. PMID:24278548

In vitro activity of novel anti-MRSA cephalosporins and comparator antimicrobial agents against staphylococci involved in prosthetic joint infections.

PubMed

Isnard, Christophe; Dhalluin, Anne; Malandain, Damasie; Bruey, Quentin; Auzou, Michel; Michon, Jocelyn; Giard, Jean-Christophe; Guérin, François; Cattoir, Vincent

2018-02-05

Ceftaroline and ceftobiprole are new parenteral cephalosporins with potent activity against methicillin-resistant (MR) staphylococci, which are the leading cause of prosthetic joint infections (PJIs). The aim of this study was to determine and compare the in vitro activities of both molecules against staphylococcal isolates recovered from clinically documented PJIs. A collection of 200 non-duplicate clinical isolates [100 Staphylococcus aureus and 100 coagulase-negative staphylococci (CoNS), including 19 and 27 MR isolates, respectively] was studied. Minimum inhibitory concentrations (MICs) of oxacillin, ceftaroline, ceftobiprole, vancomycin, teicoplanin, clindamycin, levofloxacin, linezolid and daptomycin were determined by the broth microdilution method. Bactericidal activity (at 4× MIC) of ceftaroline, ceftobiprole, vancomycin, teicoplanin, linezolid and daptomycin was assessed by time-kill assay. Among the S. aureus isolates, 100% were susceptible to ceftaroline (MIC 50/90 , 0.25/0.5μg/mL) and 98% were susceptible to ceftobiprole (MIC 50/90 , 0.5/1μg/mL), regardless of their methicillin resistance. The two ceftobiprole-non-susceptible strains (including one MRSA) showed MICs at 4mg/L. Against CoNS isolates, ceftaroline and ceftobiprole exhibited in vitro potency with MIC 50/90 values at 0.06/0.25μg/mL and 0.25/1μg/mL, respectively. At 4× MIC, ceftaroline and ceftobiprole showed rapid and marked bactericidal activity against both S. aureus and CoNS (after 24/12h and 12/6h of incubation, respectively), whilst none of the other molecules tested had a bactericidal effect by 24h. This study showed that ceftaroline and ceftobiprole have excellent in vitro activity against clinical isolates of staphylococci involved in PJIs. These molecules may therefore represent promising alternatives for the treatment of such infections. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Pheno- and genotypic analysis of antimicrobial resistance properties of Yersinia ruckeri from fish.

PubMed

Huang, Yidan; Michael, Geovana Brenner; Becker, Roswitha; Kaspar, Heike; Mankertz, Joachim; Schwarz, Stefan; Runge, Martin; Steinhagen, Dieter

2014-07-16

Enteric red-mouth disease, caused by Yersinia ruckeri, is an important disease in rainbow trout aquaculture. Antimicrobial agents are frequently used in aquaculture, thereby causing a selective pressure on bacteria from aquatic organisms under which they may develop resistance to antimicrobial agents. In this study, the distribution of minimal inhibitory concentrations (MICs) of antimicrobial agents for 83 clinical and non-clinical epidemiologically unrelated Y. ruckeri isolates from north west Germany was determined. Antimicrobial susceptibility was conducted by broth microdilution at 22 ± 2°C for 24, 28 and 48 h. Incubation for 24h at 22 ± 2°C appeared to be suitable for susceptibility testing of Y. ruckeri. In contrast to other antimicrobial agents tested, enrofloxacin and nalidixic acid showed a bimodal distribution of MICs, with one subpopulation showing lower MICs for enrofloxacin (0.008-0.015 μg/mL) and nalidixic acid (0.25-0.5 μg/mL) and another subpopulation exhibiting elevated MICs of 0.06-0.25 and 8-64 μg/mL, respectively. Isolates showing elevated MICs revealed single amino acid substitutions in the quinolone resistance-determining region (QRDR) of the GyrA protein at positions 83 (Ser83-Arg or -Ile) or 87 (Asn87-Tyr), which raised the MIC values 8- to 32-fold for enrofloxacin or 32- to 128-fold for nalidixic acid. An isolate showing elevated MICs for sulfonamides and trimethoprim harbored a ∼ 8.9 kb plasmid, which carried the genes sul2, strB and a dfrA14 gene cassette integrated into the strA gene. These observations showed that Y. ruckeri isolates were able to develop mutations that reduce their susceptibility to (fluoro)quinolones and to acquire plasmid-borne resistance genes. Copyright © 2013 Elsevier B.V. All rights reserved.

Time efficient 124I-PET volumetry in benign thyroid disorders by automatic isocontour procedures: mathematic adjustment using manual contoured measurements in low-dose CT.

PubMed

Freesmeyer, Martin; Kühnel, Christian; Westphal, Julian G

2015-01-01

Benign thyroid diseases are widely common in western societies. However, the volumetry of the thyroid gland, especially when enlarged or abnormally formed, proves to be a challenge in clinical routine. The aim of this study was to develop a simple and rapid threshold-based isocontour extraction method for thyroid volumetry from (124)I-PET/CT data in patients scheduled for radioactive iodine therapy. PET/CT data from 45 patients were analysed 30 h after 1 MBq (124)I administration. Anatomical reference volume was calculated using manually contoured data from low-dose CT images of the neck (MC). In addition, we applied an automatic isocontour extraction method (IC0.2/1.0), with two different threshold values (0.2 and 1.0 kBq/ml), for volumetry of the PET data-set. IC0.2/1.0 shape data that showed significant variation from MC data were excluded. Subsequently, a mathematical correlation using a model of linear regression with multiple variables and step-wise elimination (mIC0.2/1.0), between IC0.2/1.0 and MC, was established. Data from 41 patients (IC0.2), and 32 patients (IC1.0) were analysed. The mathematically calculated volume, mIC, showed a median deviation from the reference (MC), of ±9 % (1-54 %) for mIC0.2 and of ±8.2 % (1-50 %) for mIC1.0 CONCLUSION: Contour extraction with both, mIC1.0 and mIC0.2 gave rapid and reliable results. However, mIC0.2 can be applied to significantly more patients (>90 %) and is, therefore, deemed to be more suitable for clinical routine, keeping in mind the potential advantages of using (124)I-PET/CT for the preparation of patients scheduled for radioactive iodine therapy.

Inhibitory effect of Zataria multiflora Boiss. essential oil, alone and in combination with monolaurin, on Listeria monocytogenes

PubMed Central

Raeisi, Mojtaba; Tajik, Hossein; Razavi Rohani, Seyed Mehdi; Tepe, Bektas; Kiani, Hossein; Khoshbakht, Rahem; Shirzad Aski, Hesamaddin; Tadrisi, Hamed

2016-01-01

Listeria monocytogenes is one of the major causes of infections in developing countries. In this study, chemical composition and anti-listerial effect of the essential oil of Zataria multiflora Boiss. alone and in combination with monolaurin were evaluated at different pH values (5, 6, and 7) and temperatures (5 ˚C and 30 ˚C). Chemical composition of Zataria multiflora Boiss. essential oil was evaluated by gas chromatography-mass spectrometry (GC-MS) analysis. Minimum inhibitory concentration (MIC) of the essential oil and monolaurin were determined using microbroth dilution method and the interactions of essential oil and monolaurin were determined by the evaluation of fractional inhibitory concentrations (FIC) index. Carvacrol (63.20%) and thymol (15.10%) were found as the main components of the essential oil. The MIC values of the oil and monolaurin at pH 7 and 30 ˚C were measured as 312.50 µg mL-1 and 125.00 µg mL-1, respectively. Combination of monolaurin and Z. multiflora essential oil were found to act synergistically (FIC index < 0.5) against L. monocytogenes under different pH and temperature conditions. Decrease in the pH and temperature values have increased the anti-listerial activity of monolaurin and the essential oil. The lowest MIC value of monolaurin and essential oil was observed at pH 5 and 5 ˚C. According to our results, the oil alone or in combination with monolaurin at low pH and temperature conditions showed a promising inhibitory effect on L. monocytogenes. PMID:27226881

Inhibitory effect of Zataria multiflora Boiss. essential oil, alone and in combination with monolaurin, on Listeria monocytogenes.

PubMed

Raeisi, Mojtaba; Tajik, Hossein; Razavi Rohani, Seyed Mehdi; Tepe, Bektas; Kiani, Hossein; Khoshbakht, Rahem; Shirzad Aski, Hesamaddin; Tadrisi, Hamed

2016-01-01

Listeria monocytogenes is one of the major causes of infections in developing countries. In this study, chemical composition and anti-listerial effect of the essential oil of Zataria multiflora Boiss. alone and in combination with monolaurin were evaluated at different pH values (5, 6, and 7) and temperatures (5 ˚C and 30 ˚C). Chemical composition of Zataria multiflora Boiss. essential oil was evaluated by gas chromatography-mass spectrometry (GC-MS) analysis. Minimum inhibitory concentration (MIC) of the essential oil and monolaurin were determined using microbroth dilution method and the interactions of essential oil and monolaurin were determined by the evaluation of fractional inhibitory concentrations (FIC) index. Carvacrol (63.20%) and thymol (15.10%) were found as the main components of the essential oil. The MIC values of the oil and monolaurin at pH 7 and 30 ˚C were measured as 312.50 µg mL(-1) and 125.00 µg mL(-1), respectively. Combination of monolaurin and Z. multiflora essential oil were found to act synergistically (FIC index < 0.5) against L. monocytogenes under different pH and temperature conditions. Decrease in the pH and temperature values have increased the anti-listerial activity of monolaurin and the essential oil. The lowest MIC value of monolaurin and essential oil was observed at pH 5 and 5 ˚C. According to our results, the oil alone or in combination with monolaurin at low pH and temperature conditions showed a promising inhibitory effect on L. monocytogenes.

Comparison of antifungal activities of various essential oils on the Phytophthora drechsleri, the causal agent of fruit decay

PubMed Central

Mohammadi, Ali; Hashemi, Maryam; Hosseini, Seyed Masoud

2015-01-01

Background and Objectives: The efficacy of Mentha piperita L, Zataria multiflora Boiss and Thymus vulgaris L essential oils (EOs) was evaluated for controlling the growth of Phytophthora drechsleri, the causative agent of damage to many crops that is consumed directly by humans. Materials and Methods: The EOs used in this study was purchased from Magnolia Co, Iran. The pour plate method in petri dishes containing Potato Dextrose Agar (PDA) was used to evaluate the antifungal properties of EOs. The minimal inhibitory concentrations (MIC), minimum fungicidal concentration (MFC) as well as mycelial growth inhibition (MGI) were measured. The IC50 value (the concentration inhibited 50% of the mycelium growth) was calculated by probit analysis. Results and Conclusion: The fungal growth was significantly reduced by increasing concentrations of tested EOs. The complete reduction was obtained with Shirazi thyme at all concentrations, whereas the complete reduction for peppermint and thyme was observed at 0.4% and 0.8% (v/v) concentrations, respectively. Meanwhile, the minimum inhibition was observed when 0.1% peppermint (MGI values of 9.37%) was used. The IC50, MIC and MFC values of Shirazi thyme was 0.053, 0.1% and 0.2%, respectively. Similarly, MIC and MFC values of peppermint and thyme were recorded 0.4% and 0.8%, respectively. The results obtained from this study may contribute to the development of new antifungal agents to protect the crops from this pathogenic fungus and many agricultural plant pathogens causing drastic crop losses. PMID:26644871

Investigating the Use of the Intel Xeon Phi for Event Reconstruction

NASA Astrophysics Data System (ADS)

Sherman, Keegan; Gilfoyle, Gerard

2014-09-01

The physics goal of Jefferson Lab is to understand how quarks and gluons form nuclei and it is being upgraded to a higher, 12-GeV beam energy. The new CLAS12 detector in Hall B will collect 5-10 terabytes of data per day and will require considerable computing resources. We are investigating tools, such as the Intel Xeon Phi, to speed up the event reconstruction. The Kalman Filter is one of the methods being studied. It is a linear algebra algorithm that estimates the state of a system by combining existing data and predictions of those measurements. The tools required to apply this technique (i.e. matrix multiplication, matrix inversion) are being written using C++ intrinsics for Intel's Xeon Phi Coprocessor, which uses the Many Integrated Cores (MIC) architecture. The Intel MIC is a new high-performance chip that connects to a host machine through the PCIe bus and is built to run highly vectorized and parallelized code making it a well-suited device for applications such as the Kalman Filter. Our tests of the MIC optimized algorithms needed for the filter show significant increases in speed. For example, matrix multiplication of 5x5 matrices on the MIC was able to run up to 69 times faster than the host core. The physics goal of Jefferson Lab is to understand how quarks and gluons form nuclei and it is being upgraded to a higher, 12-GeV beam energy. The new CLAS12 detector in Hall B will collect 5-10 terabytes of data per day and will require considerable computing resources. We are investigating tools, such as the Intel Xeon Phi, to speed up the event reconstruction. The Kalman Filter is one of the methods being studied. It is a linear algebra algorithm that estimates the state of a system by combining existing data and predictions of those measurements. The tools required to apply this technique (i.e. matrix multiplication, matrix inversion) are being written using C++ intrinsics for Intel's Xeon Phi Coprocessor, which uses the Many Integrated Cores (MIC) architecture. The Intel MIC is a new high-performance chip that connects to a host machine through the PCIe bus and is built to run highly vectorized and parallelized code making it a well-suited device for applications such as the Kalman Filter. Our tests of the MIC optimized algorithms needed for the filter show significant increases in speed. For example, matrix multiplication of 5x5 matrices on the MIC was able to run up to 69 times faster than the host core. Work supported by the University of Richmond and the US Department of Energy.

A diterpenoid taxodone from Metasequoia glyptostroboides with antimycotic potential against clinical isolates of Candida species.

PubMed

Bajpai, V K; Park, Y-H; Kang, S C

2015-03-01

The increasing importance of clinical isolates of Candida species and emerging resistance of Candida species to current synthetic antifungal agents have stimulated the search for safer and more effective alternative drugs from natural sources. This study was directed towards exploring the antimycotic potential of a diterpenoid compound taxodone isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species. Antimycotic efficacy of taxodone was evaluated by disc diffusion assay, determination of minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations, and cell viability assay. To confirm a partial antimycotic mode of action of taxodone, the efficacy of taxodone was determined by measuring the release of 260 nm absorbing materials from the selected Candida species as compared to control. The taxodone at the concentration of 400 μg/disc displayed potential antimycotic effect against the tested clinical and pathogenic isolates of Candida species as diameters of zones of inhibitions, which were found in the range of 11 ± 0.0 to 12.6 ± 0.5mm. The MIC and MFC values of taxodone against the tested clinical isolates were found in the range of 250 to 1000 and 500 to 2000μ g/mL, respectively. On the other hand, the MIC and MFC values of positive control (amphotericin B) against the tested Candida isolates were found in the range of 62.5 to 250 and 500 to 2000 μg/mL. On the viable counts of the tested fungal isolates, the taxodone exerted significant antimycotic effect. Elaborative study of partial mode of action conducted onto the release of 260nm materials (DNA and RNA) revealed potential detrimental effect of taxodone on the membrane integrity of the tested pathogens at MIC concentration. With respect to the antimycotic effect of taxodone against pathogenic and clinical isolates of Candida species, it might be confirmed that bioactive compound taxodone present in M. glyptostroboides holds therapeutic value of medicinal significance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

In Vitro Activity of Twenty Commercially Available, Plant-Derived Essential Oils against Selected Dermatophyte Species.

PubMed

Nardoni, Simona; Giovanelli, Silvia; Pistelli, Luisa; Mugnaini, Linda; Profili, Greta; Pisseri, Francesca; Mancianti, Francesca

2015-08-01

The in vitro activity of twenty chemically defined essential oils (EOs) obtained from Boswellia sacra, Citrus bergamia, C. limon, C. medica, Cinnamomum zeylanicum, Eucalyptus globulus, Foeniculum vulgare, Helichrysum italicum, Illicium verum, Litsea cubeba, Mentha spicata, Myrtus communis, Ocimum basilicum, Origanum majorana, O. vulgare, Pelargonium graveolens, Rosmarinus officinalis, Santalum album, Satureja montana, and Thymus serpyllum was assayed against clinical animal isolates of Microsporum canis, Trichophyton mentagrophytes, T. erinacei, T. terrestre and Microsporum gypseum, main causative agents of zoonotic and/or environmental dermatophytoses in humans. Single main components present in high amounts in such EOs were also tested. Different dermatophyte species showed remarkable differences in sensitivity. In general, more effective EOs were T. serpyllum (MIC range 0.025%-0.25%), O. vulgare (MIC range 0.025%-0.5%) and L. cubeba (MIC range 0.025%-1.5%). F. vulgare showed a moderate efficacy against geophilic species such as M gypseum and T terrestre. Among single main components tested, neral was the most active (MIC and MFC values 5 0.25%). The results of the present study seem to be promising for an in vivo use of some assayed EOs.

In Vitro Activities of Five Antifungal Drugs Against Opportunistic Agents of Aspergillus Nigri Complex.

PubMed

Badali, Hamid; Fakhim, Hamed; Zarei, Fereshteh; Nabili, Mojtaba; Vaezi, Afsane; Poorzad, Nafiseh; Dolatabadi, Somayeh; Mirhendi, Hossein

2016-04-01

Black aspergilli, particularly Aspergillus niger and A. tubingensis, are the most common etiological agents of otomycosis followed by onychomycosis, pulmonary aspergillosis and aspergilloma. However, so far there is no systematic study on their antifungal susceptibility profiles. A collection of 124 clinical and environmental species of black aspergilli consisted of A. niger, A. tubingensis, A. uvarum. A. acidus and A. sydowii were verified by DNA sequencing of the partial β-tubulin gene. MICs of amphotericin B, itraconazole, voriconazole, posaconazole, and MECs of caspofungin were performed based on CLSI M38-A2. Posaconazole and caspofungin had the lowest MIC range (0.016-0.125 µg/ml and 0.008-0.031 µg/ml, respectively), followed by amphotericin B (0.25-4 µg/ml), voriconazole (0.125-16 µg/ml) and itraconazole (0.25 to >16) in an increasing order. Some strains of A. niger showed high MIC value for itraconazole and voriconazole (>16 µg/ml), in contrast only environmental isolates of A. tubingensis had high itraconazole MICs (>16 µg/ml). These results confirm that posaconazole and caspofungin are potential drugs for treatment of aspergillosis due to opportunistic agents of Aspergillus Nigri complex. However, in vivo efficacy remains to be determined.

Evaluation of the antimicrobial efficacy of Minthostachys verticillata essential oil and limonene against Streptococcus uberis strains isolated from bovine mastitis.

PubMed

Montironi, Ivana D; Cariddi, Laura N; Reinoso, Elina B

Bovine mastitis is a disease that causes great economic losses per year, being Streptococcus uberis the main environmental pathogen involved. The aim of the present study was to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of Minthostachys verticillata essential oil and limonene for S. uberis strains isolated from bovine mastitis. In addition, the effect of MIC on biofilm formation was analyzed. MIC values for the essential oil ranged from 14.3 to 114.5mg/ml (1.56-12.5%v/v) and MBC between 114.5 and 229mg/ml (12.5-25%v/v). MICs for limonene ranged from 3.3 to 52.5mg/ml (0.39-6.25%v/v) and MBC was 210mg/ml (25%v/v). Both compounds showed antibacterial activity and affected the biofilm formation of most of the strains tested. In conclusion, these compounds could be used as an alternative and/or complementary therapy for bovine mastitis caused by S. uberis. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

ANTIMICROBIAL AND ANTIBIOFILM EFFECTS OF EXTRACTS FROM TRAPA NATANS L., EVALUATION OF TOTAL PHENOLIC AND FLAVONOID CONTENTS AND GC-MS ANALYSIS.

PubMed

Radojevic, Ivana D; Vasic, Sava M; Dekic, Milan S; Radulovic, Niko S; Delic, Gorica T; Durdevic, Jelena S; Comic, Ljiljana R

2016-11-01

Research conducted in this study shows the applied in vitro antimicrobial and antibiofilm activity of the four extracts isolated from Trapa natans L. leaves. In this study, different methods were used (microdilution, tissue culture plate, different colorimetric methods, GC-FID and GC-MS analysis). While the water extract didn't show antibacterial activity, the acetone extract showed the strongest one. The same activity in the case of Pseudomonas aeruginosa (MIC was 313 μg/mL) was better than the activity of controls and it matched with antibiofilm activity. The effect of extracts was better on G+ bacteria (MICs were <78-625 μg/mL). For ethanol and ethyl acetate extracts all BIC values were better than MICs. Extracts showed a significant effect on Aspergillus restrictus (MICs were < 78/156 μg/mL). The GC and GC-MS analysis of the ethyl acetate extract revealed the identification of 22 compounds with (all E)-squalene (20.2%), n-alkanes and norlignan hinokiresinol among the most abundant ones. This is the first time that T. natans was studied using these methods.

Synthesis, antibacterial activity, synergistic effect, cytotoxicity, docking and molecular dynamics of benzimidazole analogues.

PubMed

Srivastava, Ritika; Gupta, Sunil K; Naaz, Farha; Singh, Anuradha; Singh, Vishal K; Verma, Rajesh; Singh, Nidhi; Singh, Ramendra K

2018-05-24

A series of 2-Cl-benzimidazole derivatives was synthesized and assessed for antibacterial activity. Antibacterial results indicated that compounds 2d, 2e, 3a, 3b, 3c, 4d and 4e showed promising activity against B. cerus, S. aureus and P. aeruginosa (MIC: 6.2 μg/mL) and excellent efficacy against E. coli (MIC: 3.1 μg/mL). Furthermore, compounds 3d and 3e displayed better activity (MIC: 3.1 μg/mL) than the reference drugs chloramphenicol and cycloheximide against gram positive and gram negative bacterial strains. The compounds 3d-e also showed better activity than the reference drug paromomycin against B. cerus and P. aeruginosa and showed similar inhibition pattern against S. aureus and E. coli. (MIC: 3.1 μg/mL). Studies on fractional inhibitory concentration (FIC) determination of compounds 1a-e, 2a-c, 4a-c and the reference antibiotic via combination approach revealed a synergistic effect as the MIC values were lowered up to 1 / 8 th to 1 / 33 rd of the original MIC. In-vitro cytotoxicity study indicated that 2-Cl-benzimidazole derivatives showed less toxicity than the reference used against PBM, CEM and Vero cell lines. Docking studies and MD simulations of compounds on bacterial protein (eubacterial ribosomal decoding A site, PDB: 1j7t) have been conducted to find the possible mode of action of the molecules. In silico ADMET evaluations of compounds 3d and 3e showed promising results comparable to the reference drugs used in this study. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro antimicrobial and antimycobacterial activity and HPLC-DAD screening of phenolics from Chenopodium ambrosioides L.

PubMed

Jesus, Roberta S; Piana, Mariana; Freitas, Robson B; Brum, Thiele F; Alves, Camilla F S; Belke, Bianca V; Mossmann, Natália Jank; Cruz, Ritiel C; Santos, Roberto C V; Dalmolin, Tanise V; Bianchini, Bianca V; Campos, Marli M A; Bauermann, Liliane de Freitas

The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5±0.20mg/g), ethyl acetate (16.5±0.37mg/g) and n-butanol (8.85±0.11mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95±0.04 and 1.04±0.01mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC=0.42mg/mL), Pseudomonas aeruginosa (MIC=34.37mg/mL), Paenibacillus apiarus (MIC=4.29mg/mL) and Paenibacillus thiaminolyticus (MIC=4.29mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625μg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates.

PubMed

Tseng, Sheng-Hsuan; Lim, Chuan Poh; Chen, Qi; Tang, Cheng Cai; Kong, Sing Teang; Ho, Paul Chi-Lui

2018-04-01

Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC 24 /MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC 24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC 24 A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC 24 /MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC 24 /MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate. Copyright © 2018 American Society for Microbiology.

Determination of Isavuconazole Susceptibility of Aspergillus and Candida Species by the EUCAST Method

PubMed Central

Howard, Susan J.; Lass-Flörl, Cornelia; Cuenca-Estrella, Manuel; Gomez-Lopez, Alicia

2013-01-01

Isavuconazole is a novel expanded-spectrum triazole, which has recently been approved by the FDA as an orphan drug to treat invasive aspergillosis and is currently being studied in phase III clinical trials for invasive candidiasis. The susceptibility of relatively few clinical isolates has been reported. In this study, the isavuconazole susceptibilities of 1,237 Aspergillus and 2,010 Candida geographically diverse clinical isolates were determined by EUCAST methodology at four European mycology laboratories, producing the largest multicenter data set thus far for this compound. In addition, a blinded collection of 30 cyp51A mutant Aspergillus fumigatus clinical isolates and 10 wild-type isolates was tested. From these two data sets, the following preliminary epidemiological cutoff (ECOFF) values were suggested: 2 mg/liter for Aspergillus fumigatus, Aspergillus terreus, and Aspergillus flavus; 4 mg/liter for Aspergillus niger; 0.25 mg/liter for Aspergillus nidulans; and 0.03 mg/liter for Candida albicans, Candida parapsilosis, and Candida tropicalis. Unfortunately, ECOFFs could not be determined for Candida glabrata or Candida krusei due to an unexplained interlaboratory MIC variation. For the blinded collection of A. fumigatus isolates, all MICs were ≤2 mg/liter for wild-type isolates. Differential isavuconazole MICs were observed for triazole-resistant A. fumigatus isolates with different cyp51A alterations: TR34/L98H mutants had elevated isavuconazole MICs, whereas isolates with G54 and M220 alterations had MICs in the wild-type range, suggesting that the efficacy of isavuconazole may not be affected by these alterations. This study will be an aid in interpreting isavuconazole MICs for clinical care and an important step in the future process of setting official clinical breakpoints. PMID:23959309

A multicentre study of meticillin-resistant Staphylococcus aureus in acute bacterial skin and skin-structure infections in China: susceptibility to ceftaroline and molecular epidemiology.

PubMed

Zhang, Hui; Xiao, Meng; Kong, Fanrong; O'Sullivan, Matthew V N; Mao, Lei-Li; Zhao, Hao-Ran; Zhao, Ying; Wang, He; Xu, Ying-Chun

2015-04-01

Ceftaroline is a novel cephalosporin with activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to investigate the susceptibility to ceftaroline of hospital-associated MRSA (HA-MRSA) isolates causing acute bacterial skin and skin-structure infections (ABSSSIs) in China and to examine their relationship by genotyping. A total of 251 HA-MRSA isolates causing ABSSSIs were collected from a multicentre study involving 56 hospitals in 38 large cities across 26 provinces in mainland China. All isolates were characterised by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, spa typing and detection of the Panton-Valentine leukocidin locus (lukS-PV and lukF-PV). Minimum inhibitory concentrations (MICs) of 14 antimicrobial agents, including ceftaroline, were determined by broth microdilution and were interpreted using Clinical and Laboratory Standards Institute breakpoints. The ceftaroline MIC50 and MIC90 values (MICs that inhibit 50% and 90% of the isolates, respectively) were 1 μg/mL and 2 μg/mL, respectively; 33.5% (n=84) of the isolates studied were ceftaroline-non-susceptible, with MICs of 2 μg/mL, but no isolate exhibited ceftaroline resistance (MIC>2 μg/mL). All of the ceftaroline-non-susceptible isolates belonged to the predominant HA-MRSA clones: 95.2% (n=80) from MLST clonal complex 8 (CC8), with the remaining 4.8% (n=4) from CC5. The high rate of non-susceptibility to ceftaroline amongst HA-MRSA causing ABSSSIs in China is concerning. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Antimicrobial activity of essential oils of cultivated oregano (Origanum vulgare), sage (Salvia officinalis), and thyme (Thymus vulgaris) against clinical isolates of Escherichia coli, Klebsiella oxytoca, and Klebsiella pneumoniae.

PubMed

Fournomiti, Maria; Kimbaris, Athanasios; Mantzourani, Ioanna; Plessas, Stavros; Theodoridou, Irene; Papaemmanouil, Virginia; Kapsiotis, Ioannis; Panopoulou, Maria; Stavropoulou, Elisavet; Bezirtzoglou, Eugenia E; Alexopoulos, Athanasios

2015-01-01

Oregano (Origanum vulgare), sage (Salvia officinalis), and thyme (Thymus vulgaris) are aromatic plants with ornamental, culinary, and phytotherapeutic use all over the world. In Europe, they are traditionally used in the southern countries, particularly in the Mediterranean region. The antimicrobial activities of the essential oils (EOs) derived from those plants have captured the attention of scientists as they could be used as alternatives to the increasing resistance of traditional antibiotics against pathogen infections. Therefore, significant interest in the cultivation of various aromatic and medicinal plants is recorded during the last years. However, to gain a proper and marketable chemotype various factors during the cultivation should be considered as the geographical morphology, climatic, and farming conditions. In this frame, we have studied the antimicrobial efficiency of the EOs from oregano, sage, and thyme cultivated under different conditions in a region of NE Greece in comparison to the data available in literature. Plants were purchased from a certified supplier, planted, and cultivated in an experimental field under different conditions and harvested after 9 months. EOs were extracted by using a Clevenger apparatus and tested for their antibacterial properties (Minimum inhibitory concentration - MIC) against clinical isolates of multidrug resistant Escherichia coli (n=27), Klebsiella oxytoca (n=7), and Klebsiella pneumoniae (n=16) strains by using the broth microdilution assay. Our results showed that the most sensitive organism was K. oxytoca with a mean value of MIC of 0.9 µg/mL for oregano EOs and 8.1 µg/mL for thyme. The second most sensitive strain was K. pneumoniae with mean MIC values of 9.5 µg/mL for thyme and 73.5 µg/mL for oregano EOs. E. coli strains were among the most resistant to EOs antimicrobial action as the observed MICs were 24.8-28.6 µg/mL for thyme and above 125 µg/mL for thyme and sage. Most efficient were the EOs from thyme followed by those of oregano. With MIC values above 150 µg/mL, sage EOs did not show any antibacterial efficiency against the majority of the strains. However, no significant differences were observed concerning the antimicrobial action of all EOs originating from irrigated versus non-irrigated cultivated aromatic plants.

Antimicrobial activity of essential oils of cultivated oregano (Origanum vulgare), sage (Salvia officinalis), and thyme (Thymus vulgaris) against clinical isolates of Escherichia coli, Klebsiella oxytoca, and Klebsiella pneumoniae

PubMed Central

Fournomiti, Maria; Kimbaris, Athanasios; Mantzourani, Ioanna; Plessas, Stavros; Theodoridou, Irene; Papaemmanouil, Virginia; Kapsiotis, Ioannis; Panopoulou, Maria; Stavropoulou, Elisavet; Bezirtzoglou, Eugenia E.; Alexopoulos, Athanasios

2015-01-01

Background Oregano (Origanum vulgare), sage (Salvia officinalis), and thyme (Thymus vulgaris) are aromatic plants with ornamental, culinary, and phytotherapeutic use all over the world. In Europe, they are traditionally used in the southern countries, particularly in the Mediterranean region. The antimicrobial activities of the essential oils (EOs) derived from those plants have captured the attention of scientists as they could be used as alternatives to the increasing resistance of traditional antibiotics against pathogen infections. Therefore, significant interest in the cultivation of various aromatic and medicinal plants is recorded during the last years. However, to gain a proper and marketable chemotype various factors during the cultivation should be considered as the geographical morphology, climatic, and farming conditions. In this frame, we have studied the antimicrobial efficiency of the EOs from oregano, sage, and thyme cultivated under different conditions in a region of NE Greece in comparison to the data available in literature. Methods Plants were purchased from a certified supplier, planted, and cultivated in an experimental field under different conditions and harvested after 9 months. EOs were extracted by using a Clevenger apparatus and tested for their antibacterial properties (Minimum inhibitory concentration – MIC) against clinical isolates of multidrug resistant Escherichia coli (n=27), Klebsiella oxytoca (n=7), and Klebsiella pneumoniae (n=16) strains by using the broth microdilution assay. Results Our results showed that the most sensitive organism was K. oxytoca with a mean value of MIC of 0.9 µg/mL for oregano EOs and 8.1 µg/mL for thyme. The second most sensitive strain was K. pneumoniae with mean MIC values of 9.5 µg/mL for thyme and 73.5 µg/mL for oregano EOs. E. coli strains were among the most resistant to EOs antimicrobial action as the observed MICs were 24.8–28.6 µg/mL for thyme and above 125 µg/mL for thyme and sage. Most efficient were the EOs from thyme followed by those of oregano. Conclusions With MIC values above 150 µg/mL, sage EOs did not show any antibacterial efficiency against the majority of the strains. However, no significant differences were observed concerning the antimicrobial action of all EOs originating from irrigated versus non-irrigated cultivated aromatic plants. PMID:25881620

Neisseria gonorrhoeae and extended-spectrum cephalosporins in California: surveillance and molecular detection of mosaic penA.

PubMed

Gose, Severin; Nguyen, Duylinh; Lowenberg, Daniella; Samuel, Michael; Bauer, Heidi; Pandori, Mark

2013-12-04

The spread of Neisseria gonorrhoeae strains with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins is a major public health problem. While much work has been performed internationally, little is known about the genetics or molecular epidemiology of N. gonorrhoeae isolates with reduced susceptibility to extended-spectrum cephalosporins in the United States. The majority of N. gonorrhoeae infections are diagnosed without a live culture. Molecular tools capable of detecting markers of extended-spectrum cephalosporin resistance are needed. Urethral N. gonorrhoeae isolates were collected from 684 men at public health clinics in California in 2011. Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime and azithromycin were determined by Etest and categorized according to the U.S. Centers for Disease Control 2010 alert value breakpoints. 684 isolates were screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive isolates were subjected to DNA sequencing of their penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity of the screening RTPCR in detecting isolates with alert value extended-spectrum cephalosporin MICs, the primers were modified to selectively amplify the mosaic XXXIV penA allele. Three mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study. N. gonorrhoeae isolates with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins are currently circulating in California. Isolates with the same NG-MAST ST, penA allele and extended-spectrum cephalosporin MICs have caused treatment failures elsewhere. The RTPCR assay presented here may be useful for the detection of N. gonorrheoae isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs in settings where antimicrobial susceptibility testing is unavailable. In an era of increasing antimicrobial resistance and decreasing culture capacity, molecular assays capable of detecting extended-spectrum cephalosporin of resistance are essential to public health.

Neisseria gonorrhoeae and extended-spectrum cephalosporins in California: surveillance and molecular detection of mosaic penA

PubMed Central

2013-01-01

Background The spread of Neisseria gonorrhoeae strains with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins is a major public health problem. While much work has been performed internationally, little is known about the genetics or molecular epidemiology of N. gonorrhoeae isolates with reduced susceptibility to extended-spectrum cephalosporins in the United States. The majority of N. gonorrhoeae infections are diagnosed without a live culture. Molecular tools capable of detecting markers of extended-spectrum cephalosporin resistance are needed. Methods Urethral N. gonorrhoeae isolates were collected from 684 men at public health clinics in California in 2011. Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime and azithromycin were determined by Etest and categorized according to the U.S. Centers for Disease Control 2010 alert value breakpoints. 684 isolates were screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive isolates were subjected to DNA sequencing of their penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity of the screening RTPCR in detecting isolates with alert value extended-spectrum cephalosporin MICs, the primers were modified to selectively amplify the mosaic XXXIV penA allele. Results Three mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study. Conclusion N. gonorrhoeae isolates with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins are currently circulating in California. Isolates with the same NG-MAST ST, penA allele and extended-spectrum cephalosporin MICs have caused treatment failures elsewhere. The RTPCR assay presented here may be useful for the detection of N. gonorrheoae isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs in settings where antimicrobial susceptibility testing is unavailable. In an era of increasing antimicrobial resistance and decreasing culture capacity, molecular assays capable of detecting extended-spectrum cephalosporin of resistance are essential to public health. PMID:24305088

Differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis

PubMed Central

Maboni, Grazieli; Gressler, Leticia T.; Espindola, Julia P.; Schwab, Marcelo; Tasca, Caiane; Potter, Luciana; de Vargas, Agueda Castagna

2015-01-01

The aim of this study was to determine the differences in the antimicrobial susceptibility profiles of Moraxella bovis, M. bovoculi and M. ovis. Thirty-two strains of Moraxella spp. isolated from cattle and sheep with infectious keratoconjunctivitis were tested via broth microdilution method to determine their susceptibility to ampicillin, cefoperazone, ceftiofur, cloxacillin, enrofloxacin, florfenicol, gentamicin, neomycin, oxytetracycline and penicillin. The results demonstrated that Moraxella spp. strains could be considered sensitive for most of the antimicrobials tested in this study, but differences between the antimicrobial susceptibility profiles of these three Moraxella species were found. M. bovis might differ from other species due to the higher MIC and MBC values it presented. PMID:26273272

Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

PubMed

Rhodes, Nathaniel J; Gardiner, Bradley J; Neely, Michael N; Grayson, M Lindsay; Ellis, Andrew G; Lawrentschuk, Nathan; Frauman, Albert G; Maxwell, Kelly M; Zembower, Teresa R; Scheetz, Marc H

2015-07-01

As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Distribution of macrolide resistance mechanisms in Bulgarian clinical isolates of Streptococcus pyogenes during the years of 2013-2016.

PubMed

Muhtarova, Adile A; Gergova, Raina T; Mitov, Ivan G

2017-09-01

Streptococcus pyogenes, or group A streptococcus (GAS), is the main etiological agent of bacterial tonsillopharyngitis and a common cause of a wide variety of other mild to severe infections. Objectives of the present study was to determine and evaluate the distribution of genetic mechanisms associated with certain phenotypes of macrolide resistance in Bulgarian GAS isolated during the years of 2013-2016. All GAS strains were screened for the macrolide resistance genes erm(A), erm(B) and mef(A), using multiplex polymerase chain reaction (PCR). The minimal inhibitory concentrations (MICs) of erythromycin, azithromycin, clarithromycin, clindamycin were determined by E-tests. Almost 23% of GAS isolates obtained in 2013-2014 and near 40% of them in 2015-2016 contained various elements of resistance. The predominant gene was mef(A), which encodes an efflux pump (M-phenotype), identified in 57.84% of the macrolide-resistant strains. The next frequently prevalent mechanism was a combination of mef(A) and erm(B) in 22.55%, which determined high-level inducible or constitutive resistance to macrolides, lincosamides and streptogramins (iMLSB or cMLSB). The highest MIC value (>256mg/L) was detected in association with erm(B) (p<0.05). The MIC range was observed to be much higher in the isolates with combinations of resistance genes vs. those with mef genes alone (p<0.05). The data about the distribution and prevalence of macrolide resistance mechanisms obtained in this study can help in the treatment of persistent and recurrent GAS infections and in the correct choice of empiric therapy. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Prevalence and genetic mechanisms of antimicrobial resistance in Staphylococcus species: A multicentre report of the indian council of medical research antimicrobial resistance surveillance network.

PubMed

Rajkumar, Sunanda; Sistla, Sujatha; Manoharan, Meerabai; Sugumar, Madhan; Nagasundaram, Niveditha; Parija, Subhash Chandra; Ray, Pallab; Bakthavatchalam, Yamuna Devi; Veeraraghavan, Balaji; Kapil, Arti; Walia, Kamini; Ohri, V C

2017-01-01

Routine surveillance of antimicrobial resistance (AMR) is an essential component of measures aimed to tackle the growing threat of resistant microbes in public health. This study presents a 1-year multicentre report on AMR in Staphylococcus species as part of Indian Council of Medical Research-AMR surveillance network. Staphylococcus species was routinely collected in the nodal and regional centres of the network and antimicrobial susceptibility testing was performed against a panel of antimicrobials. Minimum inhibitory concentration (MIC) values of vancomycin (VAN), daptomycin, tigecycline and linezolid (LNZ) against selected methicillin-resistant Staphylococcus aureus(MRSA) isolates were determined by E-test and MIC creep, if any, was determined. Resistant genotypes were determined by polymerase chain reaction for those isolates showing phenotypic resistance. The prevalence of MRSA was found to be range from moderate (21%) to high (45%) among the centres with an overall prevalence of 37.3%. High prevalence of resistance was observed with commonly used antimicrobials such as ciprofloxacin and erythromycin in all the centres. Resistance to LNZ was not encountered except for a single case. Full-blown resistance to VAN in S. aureus was not observed; however, a few VAN-intermediate S. aureus isolates were documented. The most common species of coagulase negative staphylococci (CoNS) identified was Staphylococcus haemolyticus and Staphylococcus epidermidis. Resistance among CoNS was relatively higher than S. aureus. Most phenotypically resistant organisms possessed the corresponding resistance genes. There were localised differences in the prevalence of resistance between the centres. The efficacy of the anti-MRSA antimicrobials was very high; however, almost all these antimicrobials showed evidence of creeping MIC.

Population Pharmacokinetic Analysis of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Healthy Subjects, Subjects with Various Degrees of Renal Function, and Patients with Complicated Urinary Tract Infection or Acute Uncomplicated Pyelonephritis.

PubMed

Kawaguchi, Nao; Katsube, Takayuki; Echols, Roger; Wajima, Toshihiro

2018-02-01

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to perform a population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with various degrees of renal function, and patients with complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram-negative pathogens and to calculate the fraction of the time during the dosing interval where the free drug concentration in plasma exceeds the MIC ( fT MIC ). Population PK models were developed with three renal function markers, body surface area-adjusted estimated glomerular filtration rate (eGFR), absolute eGFR, and creatinine clearance, on the basis of 2,571 plasma concentrations from 91 subjects without infection and 238 patients with infection. The population PK models with each renal function marker adequately described the plasma cefiderocol concentrations. Clear relationships of total clearance (CL) to all renal function markers were observed. Body weight and disease status (with or without infection) were also significant covariates. The CL in patients with infection was 26% higher than that in subjects without infection. The fT MIC values were more than 75% in all patients (and were 100% in most patients), suggesting that a sufficient exposure to cefiderocol was provided by the tested dose regimens (2 g every 8 h as the standard dose regimen) for the treatment of cUTI or AUP caused by Gram-negative pathogens. Copyright © 2018 Kawaguchi et al.

Antimicrobial Activity and Biocompatibility of the Psidium cattleianum Extracts for Endodontic Purposes.

PubMed

Massunari, Loiane; Novais, Renata Zoccal; Oliveira, Márcio Teixeira; Valentim, Diego; Dezan Junior, Eloi; Duque, Cristiane

2017-01-01

Psidium cattleianum (PC) has been displaying inhibitory effect against a variety of microorganisms, but this effect has not yet been tested against endodontic pathogens. The aim of this study was to evaluate the antimicrobial activity and biocompatibility of the aqueous (PCAE) and hydroethanolic (PCHE) extracts from Psidium cattleianum (PC) leaves. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) were determined using the microdilution broth method in order to analyze the antimicrobial effect against Enterococcus faecalis, Pseudomonas aeruginosa, Actinomyces israelii and Candida albicans in planktonic conditions. Biofilm assays were conducted only with the extracts that were able to determine the MLC for microorganisms in planktonic conditions. Immediate and late tissue reactions against PC extracts were evaluated using edemogenic test and histological analysis of subcutaneous implants in Wistar rats. The results showed that the MIC and MLC values ranged between 0.25 and 4 mg/mL. The MLC obtained for PCHE inhibited 100% growth of all the tested strains, except for C. albicans. PCAE had the same effect for E. faecalis and P. aeruginosa. Both PC extracts were able to eliminate E. faecalis biofilms and only the PCHE eliminated P. aeruginosa biofilms. The positive controls inhibited the growth of all tested strains in MIC and MLC essays, but no CHX tested concentrations were able to eliminate A. israelii biofilm. PCAE caused a discrete increase in the edema over time, while PCHE caused a higher initial edema, which decreased progressively. Both PCAE and PCHE extracts were biocompatible, but PCHE showed better results with slight levels of inflammation at 28 days. In conclusion, PCHE was biocompatible and presented better antimicrobial effect against important pathogens associated with persistent endodontic infections.

Molecular mechanisms of membrane impermeability in clinical isolates of Enterobacteriaceae exposed to imipenem selective pressure.

PubMed

Pavez, Monica; Vieira, Camila; de Araujo, Maria Rita; Cerda, Alvaro; de Almeida, Lara Mendes; Lincopan, Nilton; Mamizuka, Elsa Masae

2016-07-01

Intrinsic mechanisms leading to carbapenem-induced membrane impermeability and multidrug resistance are poorly understood in clinical isolates of Enterobacteriaceae. In this study, molecular behaviours during the establishment of membrane impermeability in members of the Enterobacteriaceae family under imipenem selective pressure were investigated. Clinical isolates (n = 22) exhibiting susceptibility to multiple antibiotics or characterised as extended-spectrum β-lactamase (ESBL)- or AmpC-producers were submitted to progressive passages on Mueller-Hinton agar plates containing subclinical concentrations of imipenem [0.5 × the minimum inhibitory concentration (MIC)]. Changes in outer membrane permeability were evaluated by determination of antimicrobial MICs, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and gene expression analysis related to membrane permeability (i.e. omp35-like, omp36-like and acrA) and regulatory mechanisms (i.e. marA and ompR) by quantitative reverse transcription PCR. Following imipenem induction, 73% of isolates showed increased carbapenem MICs by ≥2 doubling dilutions. At an early stage of treatment, imipenem modulated the expression of porins and efflux pump genes, represented by a reduction of 78% in omp36-like and a two-fold increase in acrA expression. Transcriptional factors marA and ompR were also affected by imipenem induction, increasing mRNA expression by 14- and 4-fold, respectively. High marA expression levels were associated with higher values of acrA expression. These results suggest that imipenem is an important factor in the development of an adaptive response to carbapenems by regulating key genes involved in the control of efflux pumps and porins, which could lead to a multidrug-resistant profile in clinical isolates, contributing to possible treatment failure. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study.

PubMed

Biedenbach, Douglas J; Badal, Robert E; Huang, Ming-Yi; Motyl, Mary; Singhal, Puneet K; Kozlov, Roman S; Roman, Arthur Dessi; Marcella, Stephen

2016-06-01

Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other β-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6-75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65->90%) compared to CLSI (52-84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. Merck & Co. Inc., Kenilworth, New Jersey, USA.

Tetraglochin andina Ciald.: A medicinal plant from the Argentinean highlands with potential use in vaginal candidiasis.

PubMed

Moreno, María Alejandra; Córdoba, Susana; Zampini, Iris Catiana; Mercado, María Inés; Ponessa, Graciela; Alberto, María Rosa; Nader-Macias, M E Fatima; Sayago, Jorge; Burgos-Edwards, Alberto; Schmeda-Hirschmann, Guillermo; Isla, María Inés

2018-04-24

The Argentinean medicinal plant Tetraglochin andina Ciald, formerly classified as T. cristatum (Britton) Rothm is used in traditional medicine by inhabitants from Argentinean northwestern highlands (Puna) to treat candidiasis and as anti-inflammatory. To assess the potential of the crude drug as an anti-Candida agent with anti-inflammatory properties. The bioactivity and phytochemical composition of a dry extract of the plant was investigated. The pharmacognostic description of the crude drug is carried out for the first time, including macroscopic and microscopic examinations of the different organs, physicochemical and extractive values (petroleum ether-, ethanol- and water-soluble). The dry extract from T. andina was evaluated as antifungal against pathogenic Candida sp. and Saccharomyces cerevisiae isolated from vaginal infections and reference strains, by the macrodilution and microdilution assays. The normal vaginal microbiome in women is characterized by the dominance of lactic acid-producing bacteria, mainly Lactobacillus spp. The effect of T. andina extract on Lactobacillus strains was also assayed. The inhibitory effect on proinflammatory enzymes (cyclooxygenase, lipoxygenase and phospholipase A 2 ) and antioxidant capacity was studied. The chemical profile was analyzed by HPLC-ESI-MS. The hydroalcoholic extract inhibited the growth of all yeasts with Minimal Inhibitory Concentration (MIC) values between 12.5 and 400 µg GAE/mL and the MIC values on Lactobacillus were higher than the MIC values against Candida isolates ( > 400 µg GAE/mL). These results indicate that the hydroalcoholic extract could be used without affecting the normal microbiota of vaginal fluid. The extract showed antioxidant activity and could modulate the inflammatory process by three pathways (sPLA 2 , COX-2, LOX). The plant extract contained high total phenolic levels (386.9±1.7 mg GAE/g dry extract) and flavonoid levels (260.4±2.7 mg GAE/g dry extract). Fifty phenolic compounds were identified by HPLC-ESI-MS. They were mainly hydrolysable and condensed tannins. The dry extract was chemically and biologically stable during one year at room temperature or 4 °C. The presence of anti-Candida and anti-inflammatory activities in Tetraglochin andina extracts give support to their traditional use for treating conditions associated with microorganism infections and inflammatory process in humans. This plant preparation could be used to design phytopharmaceutical preparations to inhibit yeast growth and moderate the inflammatory and oxidative process. Copyright © 2018 Elsevier B.V. All rights reserved.

In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order

PubMed Central

Jensen, Rasmus Hare; Meletiadis, Joseph

2015-01-01

The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5), 0.06 (≤0.03 to 0.25), and 0.125 (≤0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for posaconazole. However, in the clinical setting this may be compensated for by the higher exposure at standard dosing. PMID:26438494

Effect of different ripening stages on walnut kernel quality: antioxidant activities, lipid characterization and antibacterial properties.

PubMed

Amin, Furheen; Masoodi, F A; Baba, Waqas N; Khan, Asma Ashraf; Ganie, Bashir Ahmad

2017-11-01

Packing tissue between and around the kernel halves just turning brown (PTB) is a phenological indicator of kernel ripening at harvest in walnuts. The effect of three ripening stages (Pre-PTB, PTB and Post-PTB) on kernel quality characteristics, mineral composition, lipid characterization, sensory analysis, antioxidant and antibacterial activity were investigated in fresh kernels of indigenous numbered walnut selection of Kashmir valley "SKAU-02". Proximate composition, physical properties and sensory analysis of walnut kernels showed better results for Pre-PTB and PTB while higher mineral content was seen for kernels at Post-PTB stage in comparison to other stages of ripening. Kernels showed significantly higher levels of Omega-3 PUFA (C18:3 n3 ) and low n6/n3 ratio when harvested at Pre-PTB and PTB stages. The highest phenolic content and antioxidant activity was observed at the first stage of ripening and a steady decrease was observed at later stages. TBARS values increased as ripening advanced but did not show any significant difference in malonaldehyde formation during early ripening stages whereas it showed marked increase in walnut kernels at post-PTB stage. Walnut extracts inhibited growth of Gram-positive bacteria ( B. cereus, B. subtilis, and S. aureus ) with respective MICs of 1, 1 and 5 mg/mL and gram negative bacteria ( E. coli, P. and K. pneumonia ) with MIC of 100 mg/mL. Zone of inhibition obtained against all the bacterial strains from walnut kernel extracts increased with increase in the stage of ripening. It is concluded that Pre-PTB harvest stage with higher antioxidant activities, better fatty acid profile and consumer acceptability could be preferred harvesting stage for obtaining functionally superior walnut kernels.

Antianaerobic Activity of Sulopenem Compared to Six Other Agents ▿

PubMed Central

Ednie, Lois M.; Appelbaum, Peter C.

2009-01-01

Agar dilution MIC methodology was used to compare the activity of sulopenem with those of amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 431 anaerobes. Overall, MIC50/90 values were as follows: sulopenem, 0.25/1.0 μg/ml; amoxicillin/clavulanate, 0.5/2.0 μg/ml; ampicillin/sulbactam, 0.5/4.0 μg/ml; piperacillin/tazobactam, 0.25/8.0 μg/ml; imipenem, 0.06/1.0 μg/ml; clindamycin, 0.25/16.0 μg/ml; and metronidazole, 1.0/4.0 μg/ml. PMID:19223615

In Vitro Activity of Delafloxacin Tested against Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

PubMed Central

Rhomberg, Paul R.; Huband, Michael D.; Farrell, David J.

2016-01-01

Delafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested. MIC50 and MIC90 values against all S. pneumoniae isolates were 0.008 and 0.015 μg/ml. Delafloxacin susceptibility was not affected by β-lactamase status against H. influenzae and M. catarrhalis. PMID:27458220

Gepotidacin (GSK2140944) In Vitro Activity against Gram-Positive and Gram-Negative Bacteria

PubMed Central

Farrell, D. J.; Rhomberg, P. R.; Scangarella-Oman, N. E.; Sader, H. S.

2017-01-01

ABSTRACT Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has in vitro activity against susceptible and drug-resistant pathogens. Reference in vitro methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli. Gepotidacin in vitro activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC90 of gepotidacin for 50 S. aureus (including methicillin-resistant S. aureus [MRSA]) and 50 S. pneumoniae (including penicillin-nonsusceptible) isolates was 0.5 μg/ml, and for E. coli (n = 25 isolates), it was 4 μg/ml. Gepotidacin was bactericidal against S. aureus, S. pneumoniae, and E. coli, with MBC/MIC ratios of ≤4 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4× or 10× MIC at 24 h for all of the isolates. S. aureus regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to ≤4; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against S. aureus (≤0.6 h against MRSA and MSSA), and the PAE–sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5× MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5× MIC. These in vitro data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens. PMID:28483959

Bactericidal Effect and Pharmacodynamics of Cethromycin (ABT-773) in a Murine Pneumococcal Pneumonia Model

PubMed Central

Kim, Myo-Kyoung; Zhou, Wen; Tessier, Pamela R.; Xuan, Dawei; Ye, Min; Nightingale, Charles H.; Nicolau, David P.

2002-01-01

Cethromycin (ABT-773), a new ketolide, possesses potent in vitro activity against Streptococcus pneumoniae. The objective of this study was to investigate the in vivo bactericidal activity of cethromycin against macrolide-susceptible and -resistant S. pneumoniae in a murine pneumonia model and to describe the pharmacodynamic (PD) profile of cethromycin. Eight (two macrolide susceptible, six macrolide resistant) clinical isolates of S. pneumoniae were investigated. Cyclophosphamide administration rendered ICR mice transiently neutropenic prior to intratracheal inoculation with 0.05 ml of an S. pneumoniae suspension containing 107 to 108 CFU/ml. Oral cethromycin was initiated 12 to 14 h postinoculation over a dosage range of 0.1 to 800 mg/kg of body weight/day. Lungs from seven to eight mice per treatment and control groups were collected at 0 and 24 h posttherapy to assess bacterial density. The cumulative mortality (n = 12 to 13) was assessed at 120 h (end of therapy) and at 192 h (3 days posttherapy). Recovery of pneumococci from the lungs of infected animals prior to the initiation of therapy ranged from 4.6 to 7.2 log10 CFU. Growth in untreated control animals over a 24-h study period increased 0.3 to 2.7 log10 CFU. Cethromycin demonstrated a substantial bactericidal effect, regardless of macrolide susceptibility. Correlation between changes in bacterial density (24 h) and survival over both 120 and 192 h were statistically significant. All three PD parameters demonstrated a significant correlation with changes in log10 CFU/lung (Spearman's correlation coefficient, P < 0.001); however, the goodness of fit as assessed with the maximum effect (Emax) model revealed that the maximum concentration of free drug in serum (Cmax free)/MIC and the area under the free drug concentration-time curve (AUCfree)/MIC best explained the relationship between drug exposure and reductions in viable bacterial counts. These data reveal that an approximate cethromycin AUCfree/MIC of 50 or Cmax free/MIC of 1 results in bacteriostatic effects, while higher values (twofold) maximize survival. PMID:12234843

Measuring postnatal care contacts for mothers and newborns: An analysis of data from the MICS and DHS surveys

PubMed Central

Amouzou, Agbessi; Mehra, Vrinda; Carvajal–Aguirre, Liliana; Khan, Shane M.; Sitrin, Deborah; Vaz, Lara ME

2017-01-01

Background The postnatal period represents a vulnerable phase for mothers and newborns where both face increased risk of morbidity and death. WHO recommends postnatal care (PNC) for mothers and newborns to include a first contact within 24 hours following the birth of the child. However, measuring coverage of PNC in household surveys has been variable over time. The two largest household survey programs in low and middle–income countries, the UNICEF–supported Multiple Indicator Cluster Surveys (MICS) and USAID–funded Demographic and Health Surveys (DHS), now include modules that capture these measures. However, the measurement approach is slightly different between the two programs. We attempt to assess the possible measurement differences that might affect comparability of coverage measures. Methods We first review the standard questionnaires of the two survey programs to compare approaches to collecting data on postnatal contacts for mothers and newborns. We then illustrate how the approaches used can affect PNC coverage estimates by analysing data from four countries; Bangladesh, Ghana, Kygyz Republic, and Nepal, with both MICS and DHS between 2010–2015. Results We found that tools implemented todate by MICS and DHS (up to MICS round 5 and up to DHS phase 6) have collected PNC information in different ways. While MICS dedicated a full module to PNC and distinguishes immediate vs later PNC, DHS implemented a more blended module of pregnancy and postnatal and did not systematically distinguish those phases. The two survey programs differred in the way questions on postnatal care for mothers and newbors were framed. Subsequently, MICS and DHS surveys followed different methodological approach to compute the global indicator of postnatal contacts for mothers and newborns within two days following delivery. Regardless of the place of delivery, MICS estimates for postnatal contacts for mothers and newbors appeared consistently higher than those reported in DHS. The difference was however, far more pronounced in case of newborns. Conclusions Difference in questionnaires and the methodology adopted to measure PNC have created comparability issues in the coverage levels. Harmonization of survey instruments on postnatal contacts will allow comparable and better assessment of coverage levels and trends. PMID:29423179

Detection of Penicillin Susceptibility in Streptococcus pneumoniae by pbp2b PCR-Restriction Fragment Length Polymorphism Analysis

PubMed Central

O’Neill, A. M.; Gillespie, S. H.; Whiting, G. C.

1999-01-01

A PCR-restriction fragment length polymorphism strategy directed against the pbp2b gene was evaluated for identification of penicillin susceptibility. A total of 106 United Kingdom (U.K.), 30 Danish, and 11 Papua New Guinean strains were tested. Of the U.K. strains, all the susceptible and all but one of the resistant isolates were correctly assigned. By using conventional definitions of “not resistant” and “not susceptible,” the sensitivities were 97.5 and 94.4%, the specificities were 100 and 98.9%, the positive predictive values were 100 and 94.4%, and the negative predictive values were 93.1 and 98.9%, respectively. This technique may allow susceptible (MIC, <0.1 mg/liter) and resistant (MIC, >1 mg/liter) isolates to be distinguished in a single PCR. PMID:9854082

Investigation of the Antifungal Activity and Mode of Action of Thymus vulgaris, Citrus limonum, Pelargonium graveolens, Cinnamomum cassia, Ocimum basilicum, and Eugenia caryophyllus Essential Oils.

PubMed

Gucwa, Katarzyna; Milewski, Sławomir; Dymerski, Tomasz; Szweda, Piotr

2018-05-08

The antimicrobial activity of plant oils and extracts has been recognized for many years. In this study the activity of Thymus vulgaris , Citrus limonum , Pelargonium graveolens , Cinnamomum cassia , Ocimum basilicum , and Eugenia caryophyllus essential oils (EOs) distributed by Pollena Aroma (Nowy Dwór Mazowiecki, Poland) was investigated against a group of 183 clinical isolates of C. albicans and 76 isolates of C. glabrata . All of the oils exhibited both fungistatic and fungicidal activity toward C. albicans and C. glabrata isolates. The highest activity was observed for cinnamon oil, with MIC (Minimum Inhibitory Concentration) values in the range 0.002⁻0.125% ( v / v ). The MIC values of the rest of the oils were in the range 0.005% (or less) to 2.5% ( v / v ). In most cases MFC (Minimum Fungicidal Concentration) values were equal to MIC or twice as high. Additionally, we examined the mode of action of selected EOs. The effect on cell wall components could not be clearly proved. Three of the tested EOs (thyme, lemon, and clove) affected cell membranes. At the same time, thyme, cinnamon, and clove oil influenced potassium ion efflux, which was not seen in the case of lemon oil. All of the tested oils demonstrated the ability to inhibit the transition of yeast to mycelium form, but the effect was the lowest in the case of cinnamon oil.

Antimicrobial activity of traditional medicinal plants from Ankober District, North Shewa Zone, Amhara Region, Ethiopia.

PubMed

Lulekal, E; Rondevaldova, J; Bernaskova, E; Cepkova, J; Asfaw, Z; Kelbessa, E; Kokoska, L; Van Damme, P

2014-05-01

Traditional medicinal plants have long been used in Ethiopia to treat human and livestock ailments. Despite a well-documented rich tradition of medicinal plant use in the country, their direct antimicrobial effects are still poorly known. To investigate the antimicrobial activity of 19 medicinal plant species that were selected based on the ethnobotanical information on their traditional use to treat infectious diseases in Ankober District. About 23 different ethanol extracts of plants obtained by maceration of various parts of 19 medicinal plant species were studied for potential antimicrobial activity using a broth microdilution method against Bacillus cereus, Bacteroides fragilis, Candida albicans, Clostridium perfringens, Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella enteritidis, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. Plant extracts from Embelia schimperi Vatke (Myrsinaceae) showed the strongest antibacterial activity with a minimum inhibitory concentration (MIC) value of 64 µg/ml against B. cereus, L. monocytogenes, and S. pyogenes. Growth inhibitory activities were also observed for extracts of Ocimum lamiifolium Hochst. (Lamiaceae) against S. pyogenes, and those of Rubus steudneri Schweinf. (Rosaceae) against S. epidermidis at an MIC value of 128 µg/ml. Generally, 74% of ethanol extracts (17 extracts) showed antimicrobial activity against one or more of the microbial strains tested at an MIC value of 512 µg/ml or below. Results confirm the antimicrobial role of traditional medicinal plants of Ankober and warrant further investigations on promising medicinal plant species so as to isolate and characterise chemicals responsible for the observed strong antimicrobial activities.

The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

PubMed

Marcos-Zambrano, Laura Judith; Gómez-Perosanz, Marta; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

2017-07-01

We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital. The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay. SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P  <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P  <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment. Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antioxidant and antimicrobial activities of bitter and sweet apricot (Prunus armeniaca L.) kernels.

PubMed

Yiğit, D; Yiğit, N; Mavi, A

2009-04-01

The present study describes the in vitro antimicrobial and antioxidant activity of methanol and water extracts of sweet and bitter apricot (Prunus armeniaca L.) kernels. The antioxidant properties of apricot kernels were evaluated by determining radical scavenging power, lipid peroxidation inhibition activity and total phenol content measured with a DPPH test, the thiocyanate method and the Folin method, respectively. In contrast to extracts of the bitter kernels, both the water and methanol extracts of sweet kernels have antioxidant potential. The highest percent inhibition of lipid peroxidation (69%) and total phenolic content (7.9 +/- 0.2 microg/mL) were detected in the methanol extract of sweet kernels (Hasanbey) and in the water extract of the same cultivar, respectively. The antimicrobial activities of the above extracts were also tested against human pathogenic microorganisms using a disc-diffusion method, and the minimal inhibitory concentration (MIC) values of each active extract were determined. The most effective antibacterial activity was observed in the methanol and water extracts of bitter kernels and in the methanol extract of sweet kernels against the Gram-positive bacteria Staphylococcus aureus. Additionally, the methanol extracts of the bitter kernels were very potent against the Gram-negative bacteria Escherichia coli (0.312 mg/mL MIC value). Significant anti-candida activity was also observed with the methanol extract of bitter apricot kernels against Candida albicans, consisting of a 14 mm in diameter of inhibition zone and a 0.625 mg/mL MIC value.

Citral and carvone chemotypes from the essential oils of Colombian Lippia alba (Mill.) N.E. Brown: composition, cytotoxicity and antifungal activity.

PubMed

Mesa-Arango, Ana Cecilia; Montiel-Ramos, Jehidys; Zapata, Bibiana; Durán, Camilo; Betancur-Galvis, Liliana; Stashenko, Elena

2009-09-01

Two essential oils of Lippia alba (Mill.) N.E. Brown (Verbenacea), the carvone and citral chemotypes and 15 of their compounds were evaluated to determine cytotoxicity and antifungal activity. Cytotoxicity assays for both the citral and carvone chemotypes were carried out with tetrazolium-dye, which showed a dose-dependent cytotoxic effect against HeLa cells. Interestingly, this effect on the evaluated cells (HeLa and the non-tumoural cell line, Vero) was lower than that of commercial citral alone. Commercial citral showed the highest cytotoxic activity on HeLa cells. The antifungal activity was evaluated against Candida parapsilosis, Candida krusei, Aspergillus flavus and Aspergillus fumigatus strains following the standard protocols, Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing and CLSI M38-A. Results demonstrated that the most active essential oil was the citral chemotype, with geometric means-minimal inhibitory concentration (GM-MIC) values of 78.7 and 270.8 microg/mL for A. fumigatus and C. krusei, respectively. Commercial citral showed an antifungal activity similar to that of the citral chemotype (GM-MIC values of 62.5 microg/mL for A. fumigatus and 39.7 microg/mL for C. krusei). Although the citronellal and geraniol were found in lower concentrations in the citral chemotype, they had significant antifungal activity, with GM-MIC values of 49.6 microg/mL for C. krusei and 176.8 microg/mL for A. fumigatus.

Impact of psm-mec in the mobile genetic element on the clinical characteristics and outcome of SCCmec-II methicillin-resistant Staphylococcus aureus bacteraemia in Japan.

PubMed

Aoyagi, T; Kaito, C; Sekimizu, K; Omae, Y; Saito, Y; Mao, H; Inomata, S; Hatta, M; Endo, S; Kanamori, H; Gu, Y; Tokuda, K; Yano, H; Kitagawa, M; Kaku, M

2014-09-01

Over-expression of alpha-phenol-soluble modulins (PSMs) results in high virulence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). The psm-mec gene, located in the mobile genetic element SCCmec-II, suppresses PSMαs production. Fifty-two patients with MRSA bacteraemia were enrolled. MRSA isolates were evaluated with regard to the psm-mec gene sequence, bacterial virulence, and the minimum inhibitory concentration (MIC) of vancomycin and teicoplanin. Fifty-one MRSA isolates were classified as SCCmec-II, and 10 had one point mutation in the psm-mec promoter. We compared clinical characteristics and outcomes between mutant MRSA and wild-type MRSA. Production of PSMα3 in mutant MRSA was significantly increased, but biofilm formation was suppressed. Wild-type MRSA caused more catheter-related bloodstream infections (30/41 vs. 3/10, p 0.0028), whereas mutant MRSA formed more deep abscesses (4/10 vs. 3/41, p 0.035). Bacteraemia caused by mutant MRSA was associated with reduced 30-day mortality (1/10 vs. 13/41, p 0.25), although this difference was not significant. The MIC90 of teicoplanin was higher for wild-type MRSA (1.5 mg/L vs. 1 mg/L), but the MIC of vancomycin was not different between the two groups. The 30-day mortality of MRSA with a high MIC of teicoplanin (≥1.5 mg/L) was higher than that of strains with a lower MIC (≤0.75 mg/L) (6/10 vs. 6/33, p 0.017). Mutation of the psm-mec promoter contributes to virulence of SCCmec-II MRSA, and the product of psm-mec may determine the clinical characteristics of bacteraemia caused by SCCmec-II MRSA, but it does not affect mortality. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Glutathione may have implications in the design of 3-bromopyruvate treatment protocols for both fungal and algal infections as well as multiple myeloma

PubMed Central

Niedźwiecka, Katarzyna; Augustyniak, Daria; Majkowska-Skrobek, Grażyna; Cal-Bąkowska, Magdalena; Ko, Young H.; Pedersen, Peter L.; Goffeau, Andre

2016-01-01

In different fungal and algal species, the intracellular concentration of reduced glutathione (GSH) correlates closely with their susceptibility to killing by the small molecule alkylating agent 3-bromopyruvate (3BP). Additionally, in the case of Cryptococcus neoformans cells 3BP exhibits a synergistic effect with buthionine sulfoximine (BSO), a known GSH depletion agent. This effect was observed when 3BP and BSO were used together at concentrations respectively of 4-5 and almost 8 times lower than their Minimal Inhibitory Concentration (MIC). Finally, at different concentrations of 3BP (equal to the half-MIC, MIC and double-MIC in a case of fungi, 1 mM and 2.5 mM for microalgae and 25, 50, 100 μM for human multiple myeloma (MM) cells), a significant decrease in GSH concentration is observed inside microorganisms as well as tumor cells. In contrast to the GSH concentration decrease, the presence of 3BP at concentrations corresponding to sub-MIC values or half maximal inhibitory concentration (IC50) clearly results in increasing the expression of genes encoding enzymes involved in the synthesis of GSH in Cryptococcus neoformans and MM cells. Moreover, as shown for the first time in the MM cell model, the drastic decrease in the ATP level and GSH concentration and the increase in the amount of ROS caused by 3BP ultimately results in cell death. PMID:27582536

Glutathione may have implications in the design of 3-bromopyruvate treatment protocols for both fungal and algal infections as well as multiple myeloma.

PubMed

Niedźwiecka, Katarzyna; Dyląg, Mariusz; Augustyniak, Daria; Majkowska-Skrobek, Grażyna; Cal-Bąkowska, Magdalena; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

2016-10-04

In different fungal and algal species, the intracellular concentration of reduced glutathione (GSH) correlates closely with their susceptibility to killing by the small molecule alkylating agent 3-bromopyruvate (3BP). Additionally, in the case of Cryptococcus neoformans cells 3BP exhibits a synergistic effect with buthionine sulfoximine (BSO), a known GSH depletion agent. This effect was observed when 3BP and BSO were used together at concentrations respectively of 4-5 and almost 8 times lower than their Minimal Inhibitory Concentration (MIC). Finally, at different concentrations of 3BP (equal to the half-MIC, MIC and double-MIC in a case of fungi, 1 mM and 2.5 mM for microalgae and 25, 50, 100 μM for human multiple myeloma (MM) cells), a significant decrease in GSH concentration is observed inside microorganisms as well as tumor cells. In contrast to the GSH concentration decrease, the presence of 3BP at concentrations corresponding to sub-MIC values or half maximal inhibitory concentration (IC50) clearly results in increasing the expression of genes encoding enzymes involved in the synthesis of GSH in Cryptococcus neoformans and MM cells. Moreover, as shown for the first time in the MM cell model, the drastic decrease in the ATP level and GSH concentration and the increase in the amount of ROS caused by 3BP ultimately results in cell death.

Molecular characterization of acquired enrofloxacin resistance in Mycoplasma synoviae field isolates.

PubMed

Lysnyansky, I; Gerchman, I; Mikula, I; Gobbo, F; Catania, S; Levisohn, S

2013-07-01

The in vitro activity of enrofloxacin against 73 Mycoplasma synoviae field strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to >16 μg/ml. The estimated MIC50 and MIC90 values for enrofloxacin were 2 and 8 μg/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) of M. synoviae have MICs of ≥ 2 μg/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) in M. synoviae isolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, ≥ 1 μg/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison of vlhA molecular profiles revealed the presence of 9 different genotypes in the Israeli M. synoviae field isolates and 10 genotypes in the European isolates; only one vlhA genotype (type 4) was identified in both cohorts. Based on results of vlhA molecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistant M. synoviae isolates are suggested.

Molecular Characterization of Acquired Enrofloxacin Resistance in Mycoplasma synoviae Field Isolates

PubMed Central

Gerchman, I.; Mikula, I.; Gobbo, F.; Catania, S.; Levisohn, S.

2013-01-01

The in vitro activity of enrofloxacin against 73 Mycoplasma synoviae field strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to >16 μg/ml. The estimated MIC50 and MIC90 values for enrofloxacin were 2 and 8 μg/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) of M. synoviae have MICs of ≥2 μg/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) in M. synoviae isolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, ≥1 μg/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison of vlhA molecular profiles revealed the presence of 9 different genotypes in the Israeli M. synoviae field isolates and 10 genotypes in the European isolates; only one vlhA genotype (type 4) was identified in both cohorts. Based on results of vlhA molecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistant M. synoviae isolates are suggested. PMID:23612192

Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae

PubMed Central

Chen, Liang; Samanta, Palash; Shields, Ryan K.; Kreiswirth, Barry N.; Nguyen, M. Hong

2017-01-01

ABSTRACT We determined imipenem, imipenem-relebactam, ceftazidime, and ceftazidime-avibactam MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six isolates carried extended-spectrum β-lactamases (ESBLs). With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against metallo-β-lactamase (MBL) producers. Ceftazidime-avibactam (but not imipenem-relebactam) was active against OXA-48-like producers, including a strain not harboring any ESBL. Major OmpK36 porin mutations were independently associated with higher imipenem-relebactam MICs (P < 0.0001) and showed a trend toward independent association with higher ceftazidime-avibactam MICs (P = 0.07). The presence of variant KPC-3 was associated with ceftazidime-avibactam resistance (P < 0.0001). In conclusion, imipenem-relebactam and ceftazidime-avibactam had overlapping spectra of activity and niches in which each was superior. Major OmpK36 mutations in KPC-K. pneumoniae may provide a foundation for stepwise emergence of imipenem-relebactam and ceftazidime-avibactam resistance. PMID:28630202

Identifying Spectra of Activity and Therapeutic Niches for Ceftazidime-Avibactam and Imipenem-Relebactam against Carbapenem-Resistant Enterobacteriaceae.

PubMed

Haidar, Ghady; Clancy, Cornelius J; Chen, Liang; Samanta, Palash; Shields, Ryan K; Kreiswirth, Barry N; Nguyen, M Hong

2017-09-01

We determined imipenem, imipenem-relebactam, ceftazidime, and ceftazidime-avibactam MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six isolates carried extended-spectrum β-lactamases (ESBLs). With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against metallo-β-lactamase (MBL) producers. Ceftazidime-avibactam (but not imipenem-relebactam) was active against OXA-48-like producers, including a strain not harboring any ESBL. Major OmpK36 porin mutations were independently associated with higher imipenem-relebactam MICs ( P < 0.0001) and showed a trend toward independent association with higher ceftazidime-avibactam MICs ( P = 0.07). The presence of variant KPC-3 was associated with ceftazidime-avibactam resistance ( P < 0.0001). In conclusion, imipenem-relebactam and ceftazidime-avibactam had overlapping spectra of activity and niches in which each was superior. Major OmpK36 mutations in KPC- K. pneumoniae may provide a foundation for stepwise emergence of imipenem-relebactam and ceftazidime-avibactam resistance. Copyright © 2017 American Society for Microbiology.

Antimicrobial Activity of Serbian Propolis Evaluated by Means of MIC, HPTLC, Bioautography and Chemometrics

PubMed Central

Trifković, Jelena; Berić, Tanja; Vovk, Irena; Milojković-Opsenica, Dušanka; Stanković, Slaviša

2016-01-01

New information has come to light about the biological activity of propolis and the quality of natural products which requires a rapid and reliable assessment method such as High Performance Thin-Layer Chromatography (HPTLC) fingerprinting. This study investigates chromatographic and chemometric approaches for determining the antimicrobial activity of propolis of Serbian origin against various bacterial species. A linear multivariate calibration technique, using Partial Least Squares, was used to extract the relevant information from the chromatographic fingerprints, i.e. to indicate peaks which represent phenolic compounds that are potentially responsible for the antimicrobial capacity of the samples. In addition, direct bioautography was performed to localize the antibacterial activity on chromatograms. The biological activity of the propolis samples against various bacterial species was determined by a minimum inhibitory concentration assay, confirming their affiliation with the European poplar type of propolis and revealing the existence of two types (blue and orange) according to botanical origin. The strongest antibacterial activity was exhibited by sample 26 against Staphylococcus aureus, with a MIC value of 0.5 mg/mL, and Listeria monocytogenes, with a MIC as low as 0.1 mg/mL, which was also the lowest effective concentration observed in our study. Generally, the orange type of propolis shows higher antimicrobial activity compared to the blue type. PLS modelling was performed on the HPTLC data set and the resulting models might qualitatively indicate compounds that play an important role in the activity exhibited by the propolis samples. The most relevant peaks influencing the antimicrobial activity of propolis against all bacterial strains were phenolic compounds at RF values of 0.37, 0.40, 0.45, 0.51, 0.60 and 0.70. The knowledge gained through this study could be important for attributing the antimicrobial activity of propolis to specific chemical compounds, as well as the verification of HPTLC fingerprinting as a reliable method for the identification of compounds that are potentially responsible for antimicrobial activity. This is the first report on the activity of Serbian propolis as determined by several combined methods, including the modelling of antimicrobial activity by HPTLC fingerprinting. PMID:27272728

In vivo antibacterial effects of tretinoin-clindamycin and clindamycin alone on Propionibacterium acnes with varying clindamycin minimum inhibitory.

PubMed

Leyden, James J

2012-12-01

To quantify the antimicrobial effect of clindamycin phosphate 1.2% and tretinoin 0.025% gel and 1% clindamycin phosphate gel in patients with Propionibacterium acnes of varying sensitivity to clindamycin. Study 1 was an initial range-finding study that was neither blinded nor randomized. Study 2 was an open-label, randomized, splitface, single-center study. Both studies were conducted in Pennsylvania. Study 1 (n=20) and study 2 (n=22) involved healthy patients aged 18 years or older with initial P acnes levels #104/cm2 and minimum inhibitory concentrations (MICs) #8 μg/mL for clindamycin. Study 1, clindamycin gel applied twice daily for 6 weeks. Study 2; once-daily application with the combination gel to one cheek and clindamycin gel to the other side for 6 weeks. The comparative effectiveness of each product vs P acnes of varying sensitivity to clindamycin at 3 and 6 weeks posttreatment. For study 1, at 3 and 6 weeks, clindamycin-treated patients with MICs of %256 μg/mL showed greater reductions than those with MICs #512 μg/mL (P=.0001). Study 2 showed a significant reduction in P acnes for both products, with no differences found. Clindamycin alone was more effective in vivo in patients with MIC levels of %256 μg/mL than patients with higher MIC levels. The combination product produced a greater reduction than clindamycin alone after 6 weeks in patients with high MICs #512 μg/mL (P=.0047). These studies suggest that 1% clindamycin alone produces a varying in vivo antimicrobial effect, with a breakpoint at %256 μg/mL. Use of clindamycin phosphate 1.2% and tretinoin 0.025% gel resulted in a significantly greater in vivo antimicrobial effect than clindamycin alone in patients carrying P acnes with MICs of #512 μg/mL (P=.0047).

Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin.

PubMed

LaPlante, Kerry L; Rybak, Michael J; Tsuji, Brian; Lodise, Thomas P; Kaatz, Glenn W

2007-04-01

The potential for resistance development in Streptococcus pneumoniae secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10(8.5) to 10(9) log10 CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-susceptible isolates. The pharmacokinetics of each drug was simulated to provide a range of free areas under the concentration-time curves (fAUC) that correlated with various fluoroquinolone doses. Potential first (parC and parE)- and second-step (gyrA and gyrB) mutations in isolates with raised MICs were identified by sequence analysis. PD models simulating fAUC/MICs of 51 andgatifloxacin>moxifloxacin=gemifloxacin, which may be related to structural differences within the class.

Clonal background, resistance gene profile, and porin gene mutations modulate in vitro susceptibility to imipenem/relebactam in diverse Enterobacteriaceae.

PubMed

Gomez-Simmonds, Angela; Stump, Stephania; Giddins, Marla J; Annavajhala, Medini K; Uhlemann, Anne-Catrin

2018-06-11

Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae harboring bla KPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether CRE species and antibiotic resistance genotype influence response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem(IMI)/cilastatin. We carried out broth microdilution testing to IMI alone or in the presence of 4 μg/mL REL in 154 clinical isolates collected at a New York City hospital with high prevalence of bla KPC including Enterobacter spp. (n=96), K. pneumoniae (n=44), Escherichia coli (n=1), Serratia marcescens (n=9) and Citrobacter spp. (n=4). Resistance gene profiles and presence of major porin gene disruptions were ascertained by whole genome sequencing. Addition of REL decreased the IMI MIC to the susceptible range (≤1 μg/mL) in 88% of isolates. However, S. marcescens IMI/REL MICs were 4 to 8-fold higher than those of other organisms. Most bla KPC -positive isolates had IMI/REL MICs ≤1 μg/mL (88%), including E. cloacae ST171 (93%) and K. pneumoniae ST258 (82%). Nineteen isolates had IMI/REL MICs ≥2 μg/mL, of which 84% harbored bla KPC and one was bla NDM-1 -positive. Isolates with IMI/REL MICs ≥2 μg/mL versus ≤1 μg/mL were significantly more likely to demonstrate disruption of at least one porin gene (42% versus 19%, p =0.04), although most S. marcescens isolates (67%) had intact porin genes. In conclusion, while REL reduced IMI MICs in a majority of diverse CRE isolates including high-risk clones, chromosomal factors impacted IMI/REL susceptibilities and may contribute to elevated MICs in S. marcescens. Copyright © 2018 American Society for Microbiology.