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Sample records for generation cephalosporin antibiotic

  1. Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus

    SciTech Connect

    Nohjoh, T.; Suzuki, H.; Sawada, Y.; Sugiyama, Y.; Iga, T.; Hanano, M.

    1989-07-01

    To characterize the transport system by which cephalosporin antibiotics are accumulated by the choroid plexus, kinetic analysis of cefodizime transport was performed. Accumulation of cefodizime was against an electrochemical potential gradient via a saturable process (Km = 470 microM, Vmax = 174 nmol/ml of tissue per min) that was inhibited by metabolic inhibitors (KCN and 2,4-dinitrophenol), hypothermia, a sulfhydryl reagent (p-hydroxymer-curibenzoic acid) and anion transport inhibitors (probenecid and 4,4'-diisothiocyanostilbene -2,2'-disulfonic acid). Accumulation of cefodizime was inhibited competitively by benzylpenicillin with an inhibition constant of aproximately 100 microM. Cefodizime inhibited competitively the accumulation of benzylpenicillin with an inhibition constant of approximately 500 microM. Kinetic analysis using 16 kinds of beta-lactam antibiotics also supported the view (1) that the transport system of cefodizime is shared by benzylpenicillin and (2) that these beta-lactam antibiotics are transported via a common transport system. These findings indicate that the major transport system of cephalosporin antibiotics in the rat choroid plexus is via a carrier-mediated active anion transport process. The affinity of beta-lactam antibiotics for this transport system in the choroid plexus may be a major factor in determining their pharmacokinetics in the cerebrospinal fluid.

  2. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin

    PubMed Central

    Ray, Partha; Zhang, Tong; Pruden, Amy; Strickland, Michael; Knowlton, Katharine

    2015-01-01

    Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. β-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with “phages, prophages, transposable elements, and plasmids”, suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored. PMID:26258869

  3. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin.

    PubMed

    Chambers, Lindsey; Yang, Ying; Littier, Heather; Ray, Partha; Zhang, Tong; Pruden, Amy; Strickland, Michael; Knowlton, Katharine

    2015-01-01

    Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. ?-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with "phages, prophages, transposable elements, and plasmids", suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored. PMID:26258869

  4. Community-acquired pneumonia: impact of empirical antibiotic therapy without respiratory fluoroquinolones nor third-generation cephalosporins.

    PubMed

    Pradelli, J; Risso, K; de Salvador, F G; Cua, E; Ruimy, R; Roger, P-M

    2015-03-01

    Guidelines for inpatients with community-acquired pneumonia (CAP) propose to use respiratory fluoroquinolone (RFQ) and/or third-generation cephalosporins (Ceph-3). However, broad-spectrum antibiotic therapy is associated with the emergence of drug-resistant bacteria. We established a guideline in which RFQ and Ceph-3 were excluded as a first course. Our aim was to evaluate the impact of our therapeutic choices for CAP on the length of hospital stay (LOS) and patient outcome. This was a cohort study of patients with CAP from July 2005 to June 2014. We compared patients benefiting from our guideline established in 2008 to those receiving non-consensual antibiotics. Disease severity was evaluated through the Pneumonia Severity Index (PSI). The empirical treatment for PSI III to V was a combination therapy of amoxicillin-clavulanic acid (AMX-C) + roxithromycin (RX) or AMX + ofloxacin. Adherence to guidelines was defined by the prescription of one of these antibiotic agents. Requirement for intensive care or death defined unfavorable outcome. Among 1,370 patients, 847 were treated according to our guideline (61.8 %, group 1) and 523 without concordant therapy (38.2 %, group 2). The mean PSI was similar: 82 vs. 83, p > 0.5. The mean LOS was lower in group 1: 7.6 days vs. 9.1 days, p < 0.001. An unfavorable outcome was less frequent in group 1: 5.4 % vs. 9.9 %, p = 0.001. In logistic regression models, concordant therapy was associated with a favorable outcome: adjusted odds ratio (AOR) [95 % confidence interval (CI)] 1.85 [1.20-2.88], p = 0.005. CAP therapy without RFQ and Ceph-3 use was associated with a shorter LOS and fewer unfavorable outcomes. PMID:25273975

  5. Third-generation cephalosporins: a critical evaluation.

    PubMed

    Barriere, S L; Flaherty, J F

    1984-01-01

    Six third-generation cephalosporins--cefotaxime, moxalactam, cefoperazone, ceftizoxime, ceftriaxone, and cefmenoxime--are reviewed; covered are chemistry and structure-activity relationships, mechanism of action, spectra of activity, pharmacokinetics, clinical utility, adverse effects, and cost effectiveness. The third-generation cephalosporins have a similar mechanism of action to that of other beta-lactam antibiotics. None of the agents is particularly active against certain gram-positive bacteria, including methicillin-resistant Staphylococcus aureus; the drugs are effective against gonococci, Haemophilus influenzae, and Neisseria meningitidis. Several common gram-negative pathogens are susceptible to the third-generation cephalosporins, including Escherichia coli, Klebsiella, Citrobacter diversus, Proteus, and Morganella. About 50% of Pseudomonas aeruginosa isolates are susceptible. Only moxalactam has good activity against Bacteriodes fragilis. The pharmacokinetic profiles of the six agents reveal some important differences. The half-life of ceftriaxone allows once-daily dosing in many patients; the half-lives of ceftizoxime and cefoperazone permit dosing every 8-12 hours. Cefoperazone and ceftriaxone are highly protein bound, but the clinical relevance of this is unknown. Generally, the agents penetrate most body tissues and fluids well. Moxalactam and cefotaxime and possibly ceftriaxone effectively penetrate into the cerebrospinal fluid well. The third-generation cephalosporins have become the accepted drugs of choice for the treatment of adult gram-negative bacillary meningitis; as more experience is gained, they are likely to become the drugs of first choice for neonatal (with ampicillin) and childhood (except for moxalactam) meningitis. Serious infections of Enterobacteriaceae can be treated with these agents, thereby avoiding use of the aminoglycosides. Moxalactam is comparable with combination therapy in treating intra-abdominal infections. Adverse effects associated with use of the third-generation cephalosporins are generally similar to those that occur with other beta-lactam antibiotics with the exception of coagulopathies and the disulfiram reaction seen with moxalactam and cefoperazone. Despite the relatively high cost of the third-generation cephalosporins, they are often cost effective because of their reduced dosing frequencies, broad spectra of activity, and effectiveness in serious infections for which more toxic antibiotics have been required in the past. PMID:6432420

  6. Determination of the concentration of cephalosporin antibiotics in blood by infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Zalesskaya, G. A.; Shakhrai, S. V.; Kuchinskii, A. V.

    2007-07-01

    We studied IR spectra of blood and cephalosporin antibiotics that are widely used in medical practice. We established the spectral regions that are suitable for determining their concentration in blood. It is shown using the antibiotic cephtriacson as an example that the IR spectroscopy method allows one to determine the concentrations of antibiotics in blood in the range of practical medical interest. We examined the possible transfer of antibiotics by blood erythrocytes.

  7. CEPHALOSPORIN RESISTANCE AMONG BOVINE SALMONELLA ENTERICA SEROTYPES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Extended-spectrum *-lactamases (ESBLs) are important resistance mechanisms which affect *-lactam antibiotics, including cephalosporins. Extended-spectrum 3rd generation cephalosporins are considered drugs of choice for serious Salmonella infections. The emergence of ESBL-producing orga...

  8. Genome Sequence and Annotation of Acremonium chrysogenum, Producer of the β-Lactam Antibiotic Cephalosporin C

    PubMed Central

    Terfehr, Dominik; Dahlmann, Tim A.; Specht, Thomas; Zadra, Ivo; Kürnsteiner, Hubert

    2014-01-01

    The filamentous fungus Acremonium chrysogenum is the industrial producer of the β-lactam antibiotic cephalosporin C. Here, we present the genome sequence of strain ATCC 11550, which contains genes for 8,901 proteins, 127 tRNAs, and 22 rRNAs. Genome annotation led to the prediction of 42 gene clusters for secondary metabolites. PMID:25291769

  9. [Phenotypic and genotypic characterization of resistance to third-generation cephalosporins in Enterobacter spp].

    PubMed

    Bertona, E; Radice, M; Rodrguez, C H; Barberis, C; Vay, C; Famiglietti, A; Gutkind, G

    2005-01-01

    Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to beta-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63%) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC beta-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor approximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers. PMID:16502641

  10. Recent bioanalytical methods for quantification of third-generation cephalosporins using HPLC and LC-MS(/MS) and their applications in pharmacokinetic studies.

    PubMed

    Jin, Hyo-Eon; Jin, Su-Eon; Maeng, Han-Joo

    2014-11-01

    Third-generation cephalosporins are semi-synthetic antibiotics with enhanced activity against Gram-negative organisms. The cephalosporins in biological samples are mostly determined using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS). In recent years, numerous bioanalytical methods have been developed to improve the sensitivity and specificity of cephalosporin quantification using the powerful LC-MS/MS systems that are common in research laboratories. This review article presents recently developed bioanalytical methods by HPLC or LC-MS(/MS) for 12 third-generation cephalosporins, including five oral third-generation cephalosporins, and further discusses their application in pharmacokinetic studies of animals and humans. PMID:25294385

  11. Renal and hepatic function in rats treated with cyclosporin A in combination with gentamicin or cephalosporin antibiotics.

    PubMed Central

    Whiting, P. H.; Thomson, A. W.; Simpson, J. G.

    1983-01-01

    Sprague-Dawley rats received cyclosporin A (25 mg/kg) together with either the aminoglycoside gentamicin (50 mg/kg) or one of 3 cephalosporin antibiotics (100 mg/kg) daily for 14 days. Only minor impairment of renal or hepatic function was observed when either cyclosporin A or gentamicin was given on its own and no abnormality was seen in response to cephalosporins. However, concomitant administration of cyclosporin A and gentamicin caused acute renal failure, accompanied by cyclosporin A-induced damage to the proximal straight tubule and gentamicin-induced proximal convoluted tubular cell necrosis. In contrast, the structural abnormalities present in the 3 groups given cephalosporins in addition to cyclosporin A were attributable only to the immune suppressant. Liver functional changes previously found only at higher doses of cyclosporin A were observed in the cyclosporin A/gentamicin group and there was some evidence of possible interactions between cyclosporin A and each cephalosporin affecting liver function. The results indicate that treatment of infection with cephalosporin antibiotics or a less nephrotoxic aminoglycoside is preferable to gentamicin in cyclosporin A-treated patients. Images Fig. 4 Fig. 5 PMID:6661399

  12. Sensitive chemiluminescence determination of thirteen cephalosporin antibiotics with luminol-copper(II) reaction.

    PubMed

    Du, Jianxiu; Li, Hong

    2010-10-01

    A new chemiluminescence reaction, the luminol-Cu(2+) reaction, was investigated for the determination of thirteen (13) cephalosporin antibiotics, namely cefalexin, cefadroxil, cefradine, cefazolin sodium, cefaclor, cefuroxime axetil, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime, cefetamet pivoxil hydrochloride, cefixime, and cefpodoxime. It was found that, without adding any special oxidant, strong chemiluminescent (CL) signal could be produced from the reaction of the alkaline luminol with the above-mentioned antibiotics in the presence of Cu(2+). The experimental conditions for the reaction were carefully optimized with flow-injection mode. The detection limits are 0.3 ng/mL cefalexin, 3 ng/mL cefadroxil, 0.3 ng/mL cefradine, 0.02 μg/mL cefazolin sodium, 0.8 ng/mL cefaclor, 0.02 μg/mL cefuroxime axetil, 5 ng/mL cefotaxime sodium, 0.02 μg/mL cefoperazone sodium, 0.8 ng/mL ceftriaxone sodium, 1 ng/mL ceftazidime, 0.08 ng/mL cefetamet pivoxil hydrochloride, 0.8 ng/mL cefixime, and 2 ng/mL cefpodoxime. The proposed method was validated by direct application to commercial formulations and spiked milk samples containing cefradine. A possible reaction mechanism is also discussed. PMID:20925986

  13. Environmental fate of ceftiofur sodium, a cephalosporin antibiotic. Role of animal excreta in its decomposition

    SciTech Connect

    Gilbertson, T.J.; Hornish, R.E.; Jaglan, P.S.; Koshy, K.T.; Nappier, J.L.; Stahl, G.L.; Cazers, A.R.; Nappier, J.M.; Kubicek, M.F.; Hoffman, G.A.; Hamlow, P.J. )

    1990-03-01

    The degradation of ceftiofur sodium, a wide-spectrum cephalosporin antibiotic, was studied in the urine and feces of cattle, in three soils, and in buffers of pH 5, 7, and 9. Photodegradation was also studied. Fortification of cattle feces with ({sup 14}C)ceftiofur showed that it was quickly degraded to microbiologically inactive metabolites. Sterilization of the cattle feces inhibited the degradation of ceftiofur, which suggests that microorganisms or heat-labile substances may be responsible for the degradation. The t{sub 1/2} values of aerobic degradation of ceftiofur sodium in California, Florida, and Wisconsin soil were found to be 22.2, 49.0, and 41.4 days, respectively. Hydrolysis of ceftiofur, as measured by either HPLC or microbiological methods, was accelerated by increasing pH. The t{sub 1/2} values at pH 5, 7, and 9 were 100.3, 8.0, and 4.2 days, respectively, at 22{degree}C and dramatically increased at 47{degree}C. The photodegradation of ceftiofur, as determined by HPLC and a microbiological method, showed that after initial degradation for several days the rate of degradation was minimal, probably due to a protective film formed from degradation products. A major role for feces in the degradation of ceftiofur was observed, although other pathways of degradation such as soil, light, and water were also important.

  14. Nursing home residents and Enterobacteriaceae resistant to third-generation cephalosporins.

    PubMed

    Sandoval, Carolyn; Walter, Stephen D; McGeer, Allison; Simor, Andrew E; Bradley, Suzanne F; Moss, Lorraine M; Loeb, Mark B

    2004-06-01

    Limited data identify the risk factors for infection with Enterobacteriaceae resistant to third-generation cephalosporins among residents of long-term-care facilities. Using a nested case-control study design, nursing home residents with clinical isolates of Enterobacteriaceae resistant to third-generation cephalosporins were compared to residents with isolates of Enterobacteriaceae susceptible to third-generation cephalosporins. Data were collected on antimicrobial drug exposure 10 weeks before detection of the isolates, facility-level demographics, hygiene facilities, and staffing levels. Logistic regression models were built to adjust for confounding variables. Twenty-seven case-residents were identified and compared to 85 controls. Exposure to any cephalosporin (adjusted odds ratio [OR] 4.0, 95% confidence interval [CI] 1.2 to 13.6) and log percentage of residents using gastrostomy tubes within the nursing home (adjusted OR 3.9, 95% CI 1.3 to 12.0) were associated with having a clinical isolate resistant to third-generation cephalosporins. PMID:15207056

  15. Noninferiority trial comparing a first-generation cephalosporin with a third-generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy cows.

    PubMed

    Schukken, Y H; Zurakowski, M J; Rauch, B J; Gross, B; Tikofsky, L L; Welcome, F L

    2013-10-01

    The objective of this study was to evaluate the noninferiority of 2 intramammary treatments for nonsevere clinical mastitis. The 2 treatments were a first-generation cephalosporin (cephapirin sodium, 2 treatments 12h apart) and a third-generation cephalosporin (ceftiofur hydrochloride, treatments once a day for 5d). A total of 296 cases on 7 farms met the enrollment criteria for the study. Streptococcus dysgalactiae was the most common bacterial species identified in milk samples from cows with mild to moderate clinical mastitis, followed by Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and Klebsiella spp. Treatment was randomly allocated as either cephapirin sodium or ceftiofur hydrochloride via intramammary infusion according to label standards. Bacteriological cure was defined based on 2 posttreatment milk samples taken at 10 and 17d after enrollment. Noninferiority of cephapirin relative to ceftiofur was shown for bacteriological cure of gram-positive cases and for clinical cure of all cases. Ceftiofur showed a significantly higher bacteriological cure in gram-negative cases. Treatments showed no significant difference in bacteriological cure of all cases and in time to exit from the study, where the absence of a difference does not imply noninferiority. Based on the findings from this study, farm-specific treatment protocols that differ for gram-positive and gram-negative cased may be developed. PMID:23958017

  16. Possible transfer of plasmid mediated third generation cephalosporin resistance between Escherichia coli and Shigella sonnei in the human gut.

    PubMed

    Rashid, Harunur; Rahman, Mahbubur

    2015-03-01

    Choice of antibiotic for treatment of serious bacterial infection is rapidly diminishing by plasmid mediated transfer of antibiotic resistance. Here, we report a possible horizontal transfer of plasmid carrying third-generation-cephalosporin (TGC) resistance between Escherichia coli and Shigella sonnei. Two different types of colonies were identified in MacConkey agar plate from a faecal specimen collected from a patient with shigellosis. The colonies were identified as E. coli and S. sonnei. Both of the isolates were resistant to ampicillin, chloramphenicol, co-trimoxazole, erythromycin, azithromycin, nalidixic acid, ceftriaxone, cefixime, ceftazidime, cefotaxime and susceptible to co-amoxiclave, amikacin, imipenam, astreonam, levofloxacin, moxifloxacin, mecillinam. These two strains were positive for extended spectrum β-lactamase. We were able to transfer ESBL producing property from both ceftriaxone-resistant isolates to the ceftriaxone susceptible recipient E. coli K12 and S. sonnei. Plasmid profile analysis revealed that the first-generation E. coli K12 and S. sonnei transconjugants harbored a 50MDa R plasmid, as two-parent ESBL-producing S. sonnei and E. coli strains. Similar patterns of ESBL producing plasmid and transferable antimicrobial phenotype suggests that the ESBL producing plasmid might transferred between E. coli and S. sonnei through conjugation in the human gut. PMID:25461693

  17. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.

    PubMed

    Dickson, Scott D; Salazar, Kimberly C

    2013-08-01

    Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the ?-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure. PMID:23546989

  18. The intramammary efficacy of first generation cephalosporins against Staphylococcus aureus mastitis in mice.

    PubMed

    Demon, Dieter; Ludwig, Carolin; Breyne, Koen; Guédé, David; Dörner, Julia-Charlotte; Froyman, Robrecht; Meyer, Evelyne

    2012-11-01

    Staphylococcus aureus-induced mastitis in cattle causes important financial losses in the dairy industry due to lower yield and bad milk quality. Although S. aureus is susceptible to many antimicrobials in vitro, treatment often fails to cure the infected udder. Hence, comprehensive evaluation of antimicrobials against S. aureus mastitis is desirable to direct treatment strategies. The mouse mastitis model is an elegant tool to evaluate antimicrobials in vivo while circumventing the high costs associated with bovine experiments. An evaluation of the antimicrobial efficacy of the intramammary (imam) applied first generation cephalosporins cefalexin, cefalonium, cefapirin and cefazolin, was performed using the S. aureus mouse mastitis model. In vivo determination of the effective dose 2log(10) (ED(2log10)), ED(4log10), protective dose 50 (PD(50)) and PD(100) in mouse mastitis studies, support that in vitro MIC data of the cephalosporins did not fully concur with the in vivo clinical outcome. Cefazolin was shown to be the most efficacious first generation cephalosporin to treat S. aureus mastitis whereas the MIC data indicate that cefalonium and cefapirin were more active in vitro. Changing the excipient for imam application from mineral oil to miglyol 812 further improved the antimicrobial efficacy of cefazolin, confirming that the excipient can influence the in vivo efficacy. Additionally, statistical analysis of the variation of S. aureus-infected, excipient-treated mice from fourteen studies emphasizes the strength of the mouse mastitis model as a fast, cost-effective and highly reproducible screening tool to assess the efficacy of antimicrobial compounds against intramammary S. aureus infection. PMID:22677480

  19. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.

    PubMed

    Greninger, Alexander L; Chatterjee, Som S; Chan, Liana C; Hamilton, Stephanie M; Chambers, Henry F; Chiu, Charles Y

    2016-01-01

    Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins. PMID:26890675

  20. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance

    PubMed Central

    Chan, Liana C.; Hamilton, Stephanie M.; Chambers, Henry F.; Chiu, Charles Y.

    2016-01-01

    Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins. PMID:26890675

  1. Association of Veterinary Third-Generation Cephalosporin Use with the Risk of Emergence of Extended-Spectrum-Cephalosporin Resistance in Escherichia coli from Dairy Cattle in Japan

    PubMed Central

    Sato, Toyotaka; Okubo, Torahiko; Usui, Masaru; Yokota, Shin-ichi; Izumiyama, Satoshi; Tamura, Yutaka

    2014-01-01

    The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum ?-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporinresistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n?=?20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporinresistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporinresistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporinresistant isolates possessed plasmid-mediated ?-lactamase genes, including blaCTX-M-2 (9 isolates), blaCTX-M-14 (8 isolates), or blaCMY-2 (1 isolate); isolates possessing blaCTX-M-2 and blaCTX-M-14 were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporinresistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporinresistant ?-lactamase-expressing E. coli clones PMID:24755996

  2. A fluorogenic substrate of beta-lactamases and its potential as a probe to detect the bacteria resistant to the third-generation oxyimino-cephalosporins.

    PubMed

    Thai, Hien Bao Dieu; Yu, Jin Kyung; Park, Byung Sun; Park, Yeon-Joon; Min, Sun-Joon; Ahn, Dae-Ro

    2016-03-15

    We devised and synthesized a fluorogenic substrate of β-lactamases as a probe to detect the activity of the enzymes. Fluorescence of the probe emitted upon treatment of a β-lactamase and increased proportionally to the concentration of the enzyme, demonstrating its sensing property for the activity of the enzyme. We also showed that the probe could be utilized to assay the enzyme and to determine kinetic parameters of the enzyme. Moreover, the probe was able to detect resistance to the third-generation oxyimino-cephalosporin-derived antibiotics such as cefotaxime and ceftazidime. In particular, the probe could identify the ceftazidime-resistance in bacteria that was not detectable using conventional pH-sensing materials, indicating the practical utility of the probe. PMID:26547430

  3. Assessment of human exposure to 3rd generation cephalosporin resistant E. coli (CREC) through consumption of broiler meat in Belgium.

    PubMed

    Depoorter, P; Persoons, D; Uyttendaele, M; Butaye, P; De Zutter, L; Dierick, K; Herman, L; Imberechts, H; Van Huffel, X; Dewulf, J

    2012-09-17

    Acquired resistance of Escherichia coli to 3rd generation cephalosporin antimicrobials is a relevant issue in intensive broiler farming. In Belgium, about 35% of the E. coli strains isolated from live broilers are resistant to 3rd generation cephalosporins while over 60% of the broilers are found to be carrier of these 3rd generation cephalosporin resistant E. coli (CREC) after selective isolation. A model aimed at estimating the exposure of the consumer to CREC by consumption of broiler meat was elaborated. This model consists of different modules that simulate the farm to fork chain starting from primary production, over slaughter, processing and distribution to storage, preparation and consumption of broiler meat. Input data were obtained from the Belgian Food Safety agencies' annual monitoring plan and results from dedicated research programs or surveys. The outcome of the model using the available baseline data estimates that the probability of exposure to 1000 colony forming units (cfu) of CREC or more during consumption of a meal containing chicken meat is ca. 1.5%, the majority of exposure being caused by cross contamination in the kitchen. The proportion of CREC (within the total number of E. coli) at primary production and the overall contamination of broiler carcasses or broiler parts with E. coli are dominant factors in the consumer exposure to CREC. The risk of this exposure for human health cannot be estimated at this stage given a lack of understanding of the factors influencing the transfer of cephalosporin antimicrobial resistance genes from these E. coli to the human intestinal bacteria and data on the further consequences of the presence of CREC on human health. PMID:22938836

  4. Study on gamma and electron beam sterilization of third generation cephalosporins cefdinir and cefixime in solid state

    NASA Astrophysics Data System (ADS)

    Singh, Babita K.; Parwate, Dilip V.; Das Sarma, Indrani B.; Shukla, Sudhir K.

    2010-10-01

    The effect of gamma radiation from 60Co source and 2 MeV e-beam was studied on two thermolabile cephalosporin antibiotics viz cefdinir and cefixime in solid state. The parameters studied to assess radiolytic degradation were loss of chemical and microbiological potency, change in optical rotation, electronic and vibrational absorption characteristics, thermal behavior and color modification. ESR spectroscopic study, HPLC related impurity profile, thermogram and Raman spectrum are applied in deducing the nature of radiolytic impurities and their formation hypotheses. Cefixime is radiation sensitive, whereas cefdinir has acceptable radiation resistance at 25 kGy dose. The nature of radiolytic related impurities and their concentrations indicates that the lactam ring is not highly susceptible to direct radiation attack, which otherwise is considered very sensitive to stress (thermal, chemical and photochemical).

  5. Radiosterilization of fluoroquinolones and cephalosporins: assessment of radiation damage on antibiotics by changes in optical property and colorimetric parameters.

    PubMed

    Singh, Babita; Parwate, D V; Shukla, S K

    2009-01-01

    A most common problem encountered in radiosterilization of solid drugs is discoloration or yellowing. By pharmacopoeia method, discoloration can be assessed by measuring absorbance of solutions of irradiated solid samples at 450 nm. We propose to evaluate discoloration of solid samples directly by recording their diffuse reflectance spectra. Further, the reflectance spectrum is used to compute various color parameters: CIE XYZ tristimulus value, CIE Lab, DeltaE*(ab) (color difference), yellowness index (YI), dominant wavelength, and excitation purity by CIE method. The investigation of difference reflectance spectra and color parameters revealed that for fluoroquinolones, e-beam was more damaging than gamma radiation, whereas for cephalosporins, trend was reversed. The quantum of discoloration with gamma radiation and e-beam is found to be nearly equal when assessed by pharmacopeia method, and it is therefore inadequate to assess small color differences. The color parameters DeltaE*(ab) and DeltaYI are found to be reliable indicators of discoloration. The tolerance limits proposed in terms of DeltaE*(ab) and DeltaYI are +/-2 and +/-10 U, respectively. The dominant wavelength for all compounds has shifted to higher values indicating change in hue but defining color tolerance limit with this parameter requires adjunct excitation purity value. PMID:19145486

  6. [Review of oral cephalosporins. Basis for a rational choice].

    PubMed

    Forti, I N

    1994-01-01

    During the last 10 years, the emergence and spread of the most important and common resistant pathogens isolated from clinical infections led to the great release of new antibacterial agents. Many of new orally administered antibiotics introduced, such as newer fluoroquinolones or cephalosporins, showed a spectrum of activity and clinical efficacy for the most common clinical community infections. Therefore, therapeutic indication of a new cephalosporin is somewhat difficult to define, because the newer drugs must compete with improved properties over the previous ones. Therefore, choice of a first line antibiotic among apparently therapeutic equivalents could become questionable. The aim of this review was to compile the available data to offer help for a rational choice in confirmed infections of every particular patient condition and context based on microbiological activity, pharmacokinetic properties, clinical efficacy, safety and cost. Orally administered cephalosporins are beta-lactamic broad-spectrum antimicrobial agents that are often used empirically to treat community bacterial infections and also to treat culture-proven infections due to selected gram-positive and gram-negative microorganisms. Cephalosporins differ widely in their spectrum of activity, in vitro antimicrobial potency, microbial resistance, pharmaco-kinetic properties and cost. These differences result from modifications of the cephalosporin molecule. The substitutions on the R1, R2, R3 or R4 side chains results in changes in antimicrobial spectrum, potency, bioavailability, half-life and profile of toxicity. In general, the first-generation agents are more active against gram-positive organisms, more susceptible to B-lactamases of gram-negative producers, shorter serum half-life and lower cost than the other agents. The second-generation cephalosporins present enhanced spectrum of activity due to increased resistance to beta-lactamase enzymes and have longer serum half-life. The third-generation agents are the most active against Entero-bacteriaceae, possess a superior beta-lactamase stability against selected enzymes of multiple resistant bacteria, improved pharmacokinetic properties with extended plasma half-life, that permit once or twice daily administration and are the most expensive compared with the previous drugs. Among these new oral cephems, the addition of an ester group enhances the oral absorption from the gastrointestinal tract and provides better bioavailability as well as antimicrobial activity. The development of bacterial resistance has affected all steps of the cephalosporin mechanism of action. Expertise in the choice and use of the cephalosporins will remain a challenge for the physician, as additional investigational cephalosporins will continue to be developed and introduced into clinical practice in the near future. PMID:7658980

  7. Cephalosporins, carbapenems, and monobactams.

    PubMed

    Asbel, L E; Levison, M E

    2000-06-01

    Nonpenicillin beta-lactams exhibit a variable spectrum of antimicrobial activity, have a wide range of clinical uses and a favorable safety profile. Cefepime's twice-daily dosage and increased activity against Enterobacteriaceae may offer some advantages over older cephalosporins. The carbapenems offer a broad antimicrobial spectrum, and meropenem has an improved safety profile compared with imipenem. Aztreonam is a useful alternative for patients with aerobic gram-negative infections who are allergic to penicillin. The emergence of resistant organisms, however, is an increasing problem with the frequent use of these antibiotics. PMID:10829264

  8. Comparison of resistance to third-generation cephalosporins in Shigella between Europe-America and Asia-Africa from 1998 to 2012.

    PubMed

    Gu, B; Zhou, M; Ke, X; Pan, S; Cao, Y; Huang, Y; Zhuang, L; Liu, G; Tong, M

    2015-10-01

    We conducted a systematic review to compare resistance to third-generation cephalosporins (TGCs) in Shigella strains between Europe-America and Asia-Africa from 1998 to 2012 based on a literature search of computerized databases. In Asia-Africa, the prevalence of resistance of total and different subtypes to ceftriaxone, cefotaxime and ceftazidime increased markedly, with a total prevalence of resistance up to 14·2% [95% confidence interval (CI) 3·9-29·4], 22·6% (95% CI 4·8-48·6) and 6·2% (95% CI 3·8-9·1) during 2010-2012, respectively. By contrast, resistance rates to these TGCs in Europe-America remained relatively low--less than 1·0% during the 15 years. A noticeable finding was that certain countries both in Europe-America and Asia-Africa, had a rapid rising trend in the prevalence of resistance of S. sonnei, which even outnumbered S. flexneri in some periods. Moreover, comparison between countries showed that currently the most serious problem concerning resistance to these TGCs appeared in Vietnam, especially for ceftriaxone, China, especially for cefotaxime and Iran, especially for ceftazidime. These data suggest that monitoring of the drug resistance of Shigella strains should be strengthened and that rational use of antibiotics is required. PMID:25553947

  9. Prevalence of lactose fermenting coliforms resistant to third generation cephalosporins in cattle feedlot throughout a production cycle and molecular characterization of resistant isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Increases in incidence of human infections caused by Enterobacteriaceae resistant to 3rd generation cephalosporins (3GC) have become a public health concern. The 3GC ceftiofur is commonly used for the therapeutic treatment of feedlot cattle but the impact this practice has on public h...

  10. Characterization of Third-Generation-Cephalosporin-Resistant Shiga Toxin-Producing Strains of Escherichia coli O157:H7 in Japan.

    PubMed

    Kawahara, Ryuji; Seto, Kazuko; Taguchi, Masumi; Nakajima, Chie; Kumeda, Yuko; Suzuki, Yasuhiko

    2015-09-01

    We isolated Shiga toxin-producing Escherichia coli O157:H7 strains resistant to third-generation cephalosporins. The resistant strains harbored blaCMY-2, a plasmid-mediated AmpC ?-lactamase. Genotyping of isolates revealed the possible spread of this problematic bacterium. Results suggested the importance of the investigation and surveillance of enterobacteria with plasmids harboring blaCMY-2. PMID:26135870

  11. Prevalence and distribution of beta-lactamase coding genes in third-generation cephalosporin-resistant Enterobacteriaceae from bloodstream infections in Cambodia.

    PubMed

    Vlieghe, E R; Huang, T-D; Phe, T; Bogaerts, P; Berhin, C; De Smet, B; Peetermans, W E; Jacobs, J A; Glupczynski, Y

    2015-06-01

    Resistance to third-generation cephalosporins in Gram-negative bacteria is emerging in Asia. We report the prevalence and distribution of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase-coding genes in cefotaxime-resistant Enterobacteriaceae isolates from bloodstream infections (BSI) in Cambodia. All Enterobacteriaceae isolated from BSI in adult patients at Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia (2007-2010) were assessed. Antimicrobial susceptibility testing was carried out by disc diffusion and MicroScan according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Screening for ESBL, plasmidic AmpC and carbapenemase-coding genes was performed by multiplex polymerase chain reaction (PCR) sequencing assays. Identification of the ST131 clone was performed in all CTX-M-positive Escherichia coli, using PCR targeting the papB gene. Out of 183 Enterobacteriaceae, 91 (49.7 %) isolates (84 BSI episodes) were cefotaxime-resistant: E. coli (n?=?68), Klebsiella pneumoniae (n?=?17) and Enterobacter spp. (n?=?6). Most episodes were community-acquired (66/84; 78.3 %). ESBLs were present in 89/91 (97.8 %) cefotaxime-resistant isolates: 86 (96.6 %) were CTX-M, mainly CTX-M-15 (n?=?41) and CTX-M-14 (n?=?21). CTX-M of group 1 were frequently associated with TEM and/or OXA-1/30 coding genes and with phenotypic combined resistance to ciprofloxacin, sulphamethoxazole-trimethoprim and gentamicin (39/50, 78.0 %). Plasmidic AmpC (CMY-2 and DHA-1 types) were found alone (n?=?2) or in combination with ESBL (n?=?4). Eighteen E. coli isolates were identified as B2-ST131-O25B: 11 (61.1 %) carried CTX-M-14. No carbapenemase-coding genes were detected. ESBL among Enterobacteriaceae from BSI in Cambodia is common, mainly associated with CTX-M-15 and CTX-M-14. These findings warrant urgent action for the containment of antibiotic resistance in Cambodia. PMID:25717021

  12. In Vitro Synergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea

    PubMed Central

    Sasidharan, Nishanth Kumar; Sreekala, Sreerag Ravikumar; Jacob, Jubi; Nambisan, Bala

    2014-01-01

    Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000??g/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria in in vitro condition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria. PMID:24949457

  13. IgE Sensitization to Cephalosporins in Health Care Workers

    PubMed Central

    Kim, Jeong-Eun; Kim, Seung-Hyun; Jin, Hyun-Jung; Hwang, Eui-Kyung; Kim, Joo-Hee; Ye, Young-Min

    2012-01-01

    Purpose Cephalosporins can induce occupational allergies, such as asthma, urticaria, and anaphylaxis. We investigated the prevalence and risk factors of sensitization to cephalosporin. Methods A total of 161 health care workers (HCW), including 138 nurses and 23 pharmacists, and 86 unexposed non-atopic healthy controls were recruited from a single tertiary hospital and the general population. A questionnaire regarding work-related symptoms was administered along with skin prick tests (SPT) to the three most commonly used cephalosporins (cefotiam, ceftriaxone, and ceftizoxime). Serum specific IgE antibodies to conjugates of the three cephalosporins and human serum albumin (HSA) were measured by enzyme-linked immunosorbent assay (ELISA). Binding specificities were confirmed by ELISA inhibition tests. Results The prevalence of work-related symptoms in association with cephalosporins was 17.4%. The sensitization rate to any cephalosporin was 3.1% by SPT. Sensitization rates determined by measurement of serum specific IgE antibodies were 17.4% for any cephalosporin, 10.4% for cefotiam, 6.8% for ceftriaxone, and 3.7% for ceftizoxime. A personal history of any antibiotic allergy was a risk factor for work-related symptoms (OR, 24.93; 95% CI, 2.61-238), but not for the presence of serum specific IgE antibodies to cephalosporins (OR, 0.9; 95% CI, 0.18-4.53). A personal history of atopic dermatitis was a risk factor for the presence of serum specific IgE antibodies to cefotiam-HSA conjugate (OR, 6.30; 95% CI, 1.23-32.3). Conclusions A high cephalosporin sensitization rate (17.4%) was detected by ELISA in HCW exposed to cephalosporins. Monitoring of serum specific IgEs to cephalosporin-HSA conjugates will be useful for detecting sensitized subjects. PMID:22379603

  14. Analysis of Salmonella enterica with reduced susceptibility to the 3rd generation cephalosporin, ceftriaxone, isolated from US cattle during 2000-2004

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over the past decade enteric bacteria in Europe, Africa and Asia have become increasingly resistant to cephalosporin antimicrobials. This is largely due to the spread of genes encoding extended-spectrum ß-lactamase (ESBL) enzymes which can inactivate many cephalosporins. Recently these resistance me...

  15. Antibiotic consumption and antibiotic stewardship in Swedish hospitals

    PubMed Central

    Skoog, Gunilla; Ternhag, Anders; Giske, Christian G.

    2014-01-01

    Background The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumoniadata on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels. PMID:24724823

  16. Catalytically impaired fluorescent class C ?-lactamase enables rapid and sensitive cephalosporin detection by stabilizing fluorescence signals: implications for biosensor design.

    PubMed

    Tsang, Man-Wah; So, Pui-Kin; Liu, Sze-Yan; Tsang, Chun-Wai; Chan, Pak-Ho; Wong, Kwok-Yin; Leung, Yun-Chung

    2015-01-01

    Biosensors have found applications in many sectors including the food industry, where cephalosporin detection has played an important role in reducing the incidence of cephalosporin contamination, ensuring food safety, and reducing the spread of antibiotic resistance. Taking advantage of the specific interaction between ?-lactamase and its cephalosporin substrates/inhibitors, we previously constructed a biosensor based on a fluorescein-labeled class C ?-lactamase mutant, V211Cf, for specific and reagentless detection of cephalosporins and class C ?-lactamase inhibitors (Anal. Chem. 2011, 83, 1996-2004). Upon the addition of substrate/ inhibitor (i.e. the biosensor's analyte), the analyte induced a change in the local environment of the fluorescein molecule that was covalently tethered to a site close to the enzyme's active site (the 211 position), triggering a fluorescence enhancement of V211Cf. To improve the performance of V211Cf for better cephalosporin detection of the biosensor, we have developed Y150S/V211Cf, a derivative of V211Cf constructed by introducing the Y150S mutation to suppress the hydrolytic activity of V211Cf thereby improving the stability of the fluorescence signal. From our results, Y150S/V211Cf not only demonstrated improved fluorescence signal sustainability over V211Cf, but also showed a rapid response towards cephalothin (a first generation cephalosporin). These features make it feasible to of use Y150S/V211Cf for the rapid and specific detection of cephalosporins, and illustrate the possibilities for rational biosensor design of catalytically impaired fluorescent enzymes for rapid and sensitive analyte detection purposes. PMID:25181520

  17. Production of Cephalosporin C by Paecilomyces persicinus P-10

    PubMed Central

    Pisano, M. A.; Vellozzi, E. M.

    1974-01-01

    After the growth of Paecilomyces persicinus P-10 in a glucose-peptone medium, filtrates were collected and analyzed for antibiotic antivity. Activities against Salmonella gallinarum ATCC 3030 and Alcaligenes faecalis ATCC 8750 (penicillin N-resistant strain) were obtained. Part of the former activity was readily inactivated by penicillinase. The fraction active against A. faecalis was isolated by passage through Amberlite XAD-2 and Amberlite IRA-68. The powder eventually obtained was subjected to paper chromatography followed by bioautography, and the activity obtained corresponded to that of a sample of cephalosporin C. Thin-layer chromatography was also employed to verify the presence of cephalosporin C in the P-10 powder. The active solids were further purified by means of paper chromatography in a solvent system consisting of n-butanol-acetic acid-water (60:15:25, vol/vol). The material obtained from this procedure yielded an infrared absorption spectrum identical to that of cephalosporin C. Similarly, the ultraviolet absorption of the purified preparation coincided with that of cephalosporin C. Exposure of the purified solids to cephalosporinase resulted in rapid inactivation of the antibiotic. In addition to penicillin N and cephalosporin C, filtrates of P. persicinus P-10 also contained deacetylcephalosporin C, deacetoxycephalosporin C, and cephalosporin P. PMID:4157343

  18. Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages

    PubMed Central

    de Toro, María; Scharringa, Jelle; Dohmen, Wietske; Du, Yu; Hu, Juan; Lei, Ying; Li, Ning; Tooming-Klunderud, Ave; Heederik, Dick J. J.; Fluit, Ad C.; Bonten, Marc J. M.; Willems, Rob J. L.; de la Cruz, Fernando; van Schaik, Willem

    2014-01-01

    Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids. PMID:25522320

  19. Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages.

    PubMed

    de Been, Mark; Lanza, Val F; de Toro, Mara; Scharringa, Jelle; Dohmen, Wietske; Du, Yu; Hu, Juan; Lei, Ying; Li, Ning; Tooming-Klunderud, Ave; Heederik, Dick J J; Fluit, Ad C; Bonten, Marc J M; Willems, Rob J L; de la Cruz, Fernando; van Schaik, Willem

    2014-12-01

    Third-generation cephalosporins are a class of ?-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids. PMID:25522320

  20. Antibiotics.

    PubMed

    Hariprasad, Seenu M; Mieler, William F

    2016-01-01

    The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer-generation fluoroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine preparation. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct to the current management of ocular fungal infections. PMID:26501865

  1. An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants

    PubMed Central

    Phetsang, Wanida; Blaskovich, Mark A.T.; Butler, Mark S.; Huang, Johnny X.; Zuegg, Johannes; Mamidyala, Sreeman K.; Ramu, Soumya; Kavanagh, Angela M.; Cooper, Matthew A.

    2014-01-01

    An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile click chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structureactivity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. PMID:25023540

  2. An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants.

    PubMed

    Phetsang, Wanida; Blaskovich, Mark A T; Butler, Mark S; Huang, Johnny X; Zuegg, Johannes; Mamidyala, Sreeman K; Ramu, Soumya; Kavanagh, Angela M; Cooper, Matthew A

    2014-08-15

    An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. PMID:25023540

  3. Third-Generation-Cephalosporin-Resistant Klebsiella pneumoniae Isolates from Humans and Companion Animals in Switzerland: Spread of a DHA-Producing Sequence Type 11 Clone in a Veterinary Setting

    PubMed Central

    Wohlwend, Nadia; Francey, Thierry

    2015-01-01

    Characterization of third-generation-cephalosporin-resistant Klebsiella pneumoniae isolates originating mainly from one human hospital (n = 22) and one companion animal hospital (n = 25) in Bern (Switzerland) revealed the absence of epidemiological links between human and animal isolates. Human infections were not associated with the spread of any specific clone, while the majority of animal infections were due to K. pneumoniae sequence type 11 isolates producing plasmidic DHA AmpC. This clonal dissemination within the veterinary hospital emphasizes the need for effective infection control practices. PMID:25733505

  4. Chromatographic studies of some cephalosporins on thin layers of silica gel G-zinc ferrocyanide.

    PubMed

    Singh, Dhruv K; Maheshwari, Gunjan

    2010-10-01

    A simple, selective and precise thin-layer chromatographic method has been developed for the analysis of eight cephalosporin antibiotics, namely cephadroxil, cephalexin, cefixime, cefaclor, cefpodoxime proxetil, cefuroxime axetil, cefotaxime sodium and ceftriaxone sodium. The hR(F) values of these cephalosporins were investigated on silica gel G-zinc ferrocyanide layers. Mixing of zinc ferrocyanide with silica gel G resulted in a decrease in hR(F) values, removal of tailing and better resolutions. The influence of silica gel G-zinc ferrocyanide ratio and mobile phases on the chromatographic behavior of cephalosporins on thin layers was investigated. Cephalosporins were selectively separated in their binary and ternary synthetic mixtures and pharmaceutical formulations. Quantitative separations of cephalosporins from their synthetic mixtures were also achieved with good recoveries (97.8-100.3%). PMID:20853462

  5. Antibiotics

    MedlinePLUS

    ... or not using them properly, can add to antibiotic resistance. This happens when bacteria change and become able ... survive and re-infect you. Do not save antibiotics for later or use someone else's prescription. Centers for Disease Control and Prevention

  6. Degradation kinetics and mechanism of antibiotic ceftiofur in recycled water derived from beef farm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ceftiofur is a third-generation cephalosporin antibiotic that has been widely used to treat bacterial infections in concentrated animal feeding operations (CAFOs). Land application of CAFO waste may lead to the loading of ceftiofur residues and its metabolites to the environment. To mitigate the pot...

  7. [Prophylactic antibiotics in neurosurgery].

    PubMed

    Iacob, G; Iacob, Simona; Cojocaru, Inimioara

    2007-01-01

    Because of a low risk of infection (around 2-3%), prophylactic use of antibiotics in neurosurgery is a controversial issue. Some neurosurgeons consider that there are strong arguments against the use of antimicrobials (promotion of antibiotic-resistant strains of bacteria, superinfection and adverse drug reactions) and meticulous aseptic techniques could be more usefully than prophylactic antibiotics. On the other hand, despite of being rare, the consequences of a neurosurgical infection can be dramatic and may result in a rapid death, caused by meningitis, cerebritis, abscess formation or sepsis. Clinical studies emphasized that the most important factors influencing the choice of antibiotic prophylaxis in neurosurgery is the patient's immune status, virulence of the pathogens and the type of surgery ("clean contaminated"--procedure that crosses the cranial sinuses, "clean non-implant"--procedure that does not cross the cranial sinuses, CSF shunt surgery, skull fracture). Prophylaxis has become the standard of care for contaminated and clean-contaminated surgery, also for surgery involving insertion of artificial devices. The antibiotic (first/second generation of cephalosporins or vancomycin in allergic patients) should recover only the cutaneous possibly contaminating flora (S. aureus, S. epidermidis) and should be administrated 30' before the surgical incision, intravenously in a single dose. Most studies pointed that identification of the risk factors for infections, correct asepsis and minimal prophylactic antibiotic regimen, help neurosurgeons to improve patient care and to decrease mortality without selecting resistant bacteria. PMID:18293694

  8. Susceptibility of "enterobacteria" to penicillins, cephalosporins, lincomycins, erythromycin, and rifampin.

    PubMed

    Finland, M; Garner, C; Wilcox, C; Sabath, L D

    1976-08-01

    Agar dilution tests for susceptibility of gram-negative rods and enterococci were done with a number of penicillins, cephalosporins, lincomycin analogues, erythromycin, and rifampin. Many in the first three categories were investigational drugs. All were generally less active than aminoglycoside and tetracycline antibiotics against gram-negative rods and more active against enterococci. Cephalosporins as a group were more active than penicillins against Klebsiella pneumoniae and Escherichia coli and less active enterococci. Both groups were equally active against Enterobacter, Proteus, and Providencia but inactive against most strains of Serratia and all strains of Pseudomonas; however, ticarcillin, carbenicillin, and BL-1654 were active against most strains of Pseudomonas. Penicillins and cephalosporins were more active against Proteus mirabilis than against indole-positive Proteus. Lincomycins had little or no activity against gram-negative rods but were moderately active against enterococci. Erythromycin was more active than the lincomycins, but rifampin was much more active than either of these types of drug. Of the penicillins, ticarcillin, carbenicillin, and BL-P1654 were the most active against gram-negative rods, whereas BL-P1654, amoxicillin, and ampicillin were the most active against enterococci. The penicillinase-resistant penicillins, cyclacillin, and penicillin V were essentially inactive against gram-negative rods. Of the cephalosporins tested, cephanone and cefamandole were the most active against most gram-negative rods, whereas cephaloridine and cephacetrile were the most active against enterococci. The least active of the cephalosporins against most species were cephradine, cephalexin, and cephapirin, but cefoxitin was the least active against enterococci. PMID:823280

  9. [Ceftaroline, a new broad-spectrum cephalosporin in the era of multiresistance].

    PubMed

    Horcajada, Juan Pablo; Cantn, Rafael

    2014-03-01

    Antimicrobial resistance has increased during the last few years, representing a public health concern. Among Gram-positive organisms, methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae are paradigms of resistance and of the dispersion of multiresistant clones. Ceftaroline, a broad-spectrum cephalosporin that includes MRSA and penicillin-resistant S. pneumoniae, is the first ?-lactam antibiotic useful in infections due to MRSA. Phase-III clinical trials have demonstrated its efficacy in the treatment of community-acquired pneumonia and in skin and soft tissue infections, which are the current indications for ceftaroline. Due to its microbiological and pharmacological (PK/PD) profiles, these indications could be expanded to include bacteremia, endocarditis, and even osteoarticular infections. Another notable feature is the activity of this drug against Gram-negative bacilli susceptible to third generation cephalosporins, indicating that ceftaroline could be useful when these organisms are suspected or demonstrated in polymicrobial infections. Clinical follow-up of ceftaroline use will more clearly define future ceftaroline indications. PMID:24702972

  10. Do antibiotic residues in soils play a role in amplification and transmission of antibiotic resistant bacteria in cattle populations?

    PubMed Central

    Call, Douglas R.; Matthews, Louise; Subbiah, Murugan; Liu, Jinxin

    2013-01-01

    When we consider factors that contribute to the emergence, amplification, and persistence of antibiotic resistant bacteria, the conventional assumption is that antibiotic use is the primary driver in these processes and that selection occurs primarily in the patient or animal. Evidence suggests that this may not always be the case. Experimental trials show that parenteral administration of a third-generation cephalosporin (ceftiofur) in cattle has limited or short-term effects on the prevalence of ceftiofur-resistant bacteria in the gastrointestinal tract. While this response may be sufficient to explain a pattern of widespread resistance to cephalosporins, approximately two-thirds of ceftiofur metabolites are excreted in the urine raising the possibility that environmental selection plays an important additive role in the amplification and maintenance of antibiotic resistant E. coli on farms. Consequently, we present a rationale for an environmental selection hypothesis whereby excreted antibiotic residues such as ceftiofur are a significant contributor to the proliferation of antibiotic resistant bacteria in food animal systems. We also present a mathematical model of our hypothesized system as a guide for designing experiments to test this hypothesis. If supported for antibiotics such as ceftiofur, then there may be new approaches to combat the proliferation of antibiotic resistance beyond the prudent use mantra. PMID:23874327

  11. Quinolone and Cephalosporin Resistance in Enteric Fever

    PubMed Central

    Capoor, Malini Rajinder; Nair, Deepthi

    2010-01-01

    Enteric fever is a major public health problem in developing countries. Ciprofloxacin resistance has now become a norm in the Indian subcontinent. Novel molecular substitutions may become frequent in future owing to selective pressures exerted by the irrational use of ciprofloxacin in human and veterinary therapeutics, in a population endemic with nalidixic acid-resistant strains. The therapeutics of ciprofloxacin-resistant enteric fever narrows down to third- and fourth-generation cephalosporins, azithromycin, tigecycline and penems. The first-line antimicrobials ampicillin, chloramphenicol and co-trimoxazole need to be rolled back. Antimicrobial surveillance coupled with molecular analysis of fluoroquinolone resistance is warranted for reconfirming novel and established molecular patterns for therapeutic reappraisal and for novel-drug targets. This review explores the antimicrobial resistance and its molecular mechanisms, as well as novel drugs in the therapy of enteric fever. PMID:20927288

  12. [Antibiotic prophylaxis in visceral and urologic pdiatric surgery].

    PubMed

    Haas, H; Schneider, G; Moulin, F

    2013-11-01

    Surgical site infections are the leading cause of perioperative morbidity and mortality as well as increased costs following surgery. Among preventive measures, antibiotic prophylaxis significantly decreases this risk. Adult guidelines have recently been published. Specific pdiatric data are scarce, but adult recommendations can be used by extrapolation except for the neonates. For procedures that may warrant antimicrobial prophylaxis, agents of choice are first-generation cephalosporins who are not currently used in curative treatment, like cefazolin, with an appropriate dosing. A single perioperative dose of antibiotics is often sufficient. Continuation for more than 24 hours is rarely advised. PMID:24360304

  13. A seven year survey of antibiotic susceptibility and its relationship with usage.

    PubMed

    Courcol, R J; Pinkas, M; Martin, G R

    1989-03-01

    Bacterial susceptibilities to 14 antibiotics of 7385 clinical isolates, belonging to six species of Gram-negative bacilli, were analysed during seven years (1980-86). The recovery of Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa increased while their sensitivity to antibiotics decreased significantly, especially to aminoglycosides and tetracycline. There were significant correlations between increase in antibiotic use and decrease in susceptibility. There was a striking relationship between third-generation cephalosporin use and increasing number of isolates of the species mentioned above. PMID:2732126

  14. In Vitro Selection of Neisseria gonorrhoeae Mutants with Elevated MIC Values and Increased Resistance to Cephalosporins

    PubMed Central

    Grad, Yonatan; Ganakammal, Satishkumar Ranganathan; Burroughs, Mark; Frace, Mike; Lipsitch, Marc; Weil, Ryan; Trees, David

    2014-01-01

    Strains of Neisseria gonorrhoeae with mosaic penA genes bearing novel point mutations in penA have been isolated from ceftriaxone treatment failures. Such isolates exhibit significantly higher MIC values to third-generation cephalosporins. Here we report the in vitro isolation of two mutants with elevated MICs to cephalosporins. The first possesses a point mutation in the transpeptidase region of the mosaic penA gene, and the second contains an insertion mutation in pilQ. PMID:25199775

  15. Antibiotic-associated encephalopathy.

    PubMed

    Bhattacharyya, Shamik; Darby, R Ryan; Raibagkar, Pooja; Gonzalez Castro, L Nicolas; Berkowitz, Aaron L

    2016-03-01

    Delirium is a common and costly complication of hospitalization. Although medications are a known cause of delirium, antibiotics are an underrecognized class of medications associated with delirium. In this article, we comprehensively review the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE). AAE can be divided into 3 unique clinical phenotypes: encephalopathy commonly accompanied by seizures or myoclonus arising within days after antibiotic administration (caused by cephalosporins and penicillin); encephalopathy characterized by psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation of antibiotics (caused by metronidazole). We correlate these 3 clinical phenotypes with underlying pathophysiologic mechanisms of antibiotic neurotoxicity. Familiarity with these types of antibiotic toxicity can improve timely diagnosis of AAE and prompt antibiotic discontinuation, reducing the time patients spend in the delirious state. PMID:26888997

  16. Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA)

    PubMed Central

    Duplessis, Christopher; Crum-Cianflone, Nancy F.

    2011-01-01

    Microbial resistance has reached alarming levels, threatening to outpace the ability to counter with more potent antimicrobial agents. In particular, methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of skin and soft-tissue infections and PVL-positive strains have been associated with necrotizing pneumonia. Increasing reports of growing resistance to glycopeptides have been noted, further limiting the efficacy of standard antibiotics, such as vancomycin. Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum activity against Gram-positive bacteria, including MRSA and extensively-resistant strains, such as vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and vancomycin-resistant S. aureus (VRSA). In addition to being an exciting new agent in the anti-MRSA armamentarium, ceftaroline provides efficacy against many respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Ceftaroline (600 mg intravenously every 12 hours) has been shown effective in phase III studies in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia. To date, this unique antibiotic exhibits a low propensity for inducing resistance and has a good safety profile, although further post-marketing data and clinical experience are needed. In summary, ceftaroline provides an additional option for the management of complex multidrug resistant infections, including MRSA. PMID:21785568

  17. Impact of the administration of a third-generation cephalosporin (3GC) to one-day-old chicks on the persistence of 3GC-resistant Escherichia coli in intestinal flora: An in vivo experiment.

    PubMed

    Baron, Sandrine; Jouy, Eric; Touzain, Fabrice; Bougeard, Stéphanie; Larvor, Emeline; de Boisseson, Claire; Amelot, Michel; Keita, Alassane; Kempf, Isabelle

    2016-03-15

    The aim of the experiment was to evaluate under controlled conditions the impact on the excretion of 3GC-resistant Escherichia coli of the injection of one-day-old chicks with ceftiofur, a third-generation cephalosporin (3GC). Three isolators containing specific-pathogen-free chicks were used. In the first one, 20 birds were injected with ceftiofur then ten of them were orally inoculated with a weak inoculum of a 3GC-resistant E. coli field isolate containing an IncI1/ST3 plasmid encoding a blaCTX-M-1 beta-lactamase. The other chicks were kept as contact birds. None of the 20 birds in the second isolator were injected with ceftiofur, but ten of them were similarly inoculated with the 3GC-resistant strain and the others kept as contact birds. A third isolator contained ten non-injected, non-inoculated chicks. Fecal samples were collected regularly over one month and the E. coli isolated on non-supplemented media were characterized by antimicrobial agar dilution, detection of selected resistance genes and determination of phylogenetic group by PCR. The titers of 3GC-resistant E. coli in individual fecal samples were evaluated by culturing on 3GC-supplemented media. Results showed that the inoculated strain rapidly and abundantly colonized the inoculated and contact birds. The ceftiofur injection resulted in significantly higher percentages of 3GC-resistant E. coli isolates among the analyzed E. coli. No transfer of the 3GC-encoding plasmid to other isolates could be evidenced. In conclusion, these results highlight the dramatic capacity of 3GC-resistant E. coli to colonize and persist in chicks, and the selecting pressure imposed by the off-label use of ceftiofur. PMID:26931388

  18. Understanding the patterns of antibiotic susceptibility of bacteria causing urinary tract infection in West Bengal, India

    PubMed Central

    Saha, Sunayana; Nayak, Sridhara; Bhattacharyya, Indrani; Saha, Suman; Mandal, Amit K.; Chakraborty, Subhanil; Bhattacharyya, Rabindranath; Chakraborty, Ranadhir; Franco, Octavio L.; Mandal, Santi M.; Basak, Amit

    2014-01-01

    Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of empirical therapy, the susceptibility of antibiotics and resistance pattern of bacteria responsible for UTI in West Bengal, India, were evaluated throughout the period of 20082013. The infection reports belonging to all age groups and both sexes were considered. Escherichia coli was the most abundant uropathogen with a prevalence rate of 67.1%, followed by Klebsiella spp. (22%) and Pseudomonas spp. (6%). Penicillin was least effective against UTI-causing E. coli and maximum susceptibility was recorded for the drugs belonging to fourth generation cephalosporins. Other abundant uropathogens, Klebsiella spp., were maximally resistant to broad-spectrum penicillin, followed by aminoglycosides and third generation cephalosporin. The antibiotic resistance pattern of two principal UTI pathogens, E. coli and Klebsiella spp. in West Bengal, appears in general to be similar to that found in other parts of the Globe. Higher than 50% resistance were observed for broad-spectrum penicillin. Fourth generation cephalosporin and macrolides seems to be the choice of drug in treating UTIs in Eastern India. Furthermore, improved maintenance of infection incident logs is needed in Eastern Indian hospitals in order to facilitate regular surveillance of the occurrence of antibiotic resistance patterns, since such levels continue to change. PMID:25278932

  19. In silico analysis of different generation ? lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.

    PubMed

    Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

    2014-12-01

    Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for ?-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of ?-lactam antibiotics and concluded that the third generation of ?-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced ?-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis. PMID:25118647

  20. Analysis of cephalosporins by hydrophilic interaction chromatography.

    PubMed

    Liu, Qiaoxia; Xu, Lingyan; Ke, Yanxiong; Jin, Yu; Zhang, Feifang; Liang, Xinmiao

    2011-02-20

    A simple hydrophilic interaction chromatography (HILIC) method was developed to analyze seven cephalosporins. These seven cephalosporins could be separated well on the Click β-CD column and Atlantis HILIC Silica column. The effects of buffer concentration and pH on the retention under HILIC mode were studied. Except cefepime hydrochloride (4), the retention of other six cephalosporins increased with increasing buffer concentration, while decreased with increasing pH. Different separation selectivities could be observed on the Click β-CD column and Atlantis HILIC Silica column, and changing pH also resulted in the changing of separation selectivity. The separations of cephalosporins by HILIC and reversed-phase high performance liquid chromatography (RP-HPLC) were compared, and the two separation modes had good orthogonality. In addition, cefotaxime sodium (1) and its degradation were separated well on the Click β-CD column, which indicated that the Click β-CD column by HILIC can be used for studying the stability of cephalosporins. PMID:21035295

  1. A novel cephalosporin deacetylating acetyl xylan esterase from Bacillus subtilis with high activity toward cephalosporin C and 7-aminocephalosporanic acid.

    PubMed

    Tian, Qianqian; Song, Ping; Jiang, Ling; Li, Shuang; Huang, He

    2014-03-01

    A cephalosporin deacetylating acetyl xylan esterase was cloned from the genomic DNA of Bacillus subtilis CICC 20034 and functionally expressed in Escherichia coli. Its gene contained an open reading frame of 957 bp encoding 318 amino acids with a calculated mass of 35,607 Da, and it displayed significant identity to acetyl xylan esterases from Bacillus sp. 916, B. subtilis 168, and Bacillus pumilus Cect5072. The enzyme was a native homohexamer but a trimer under the condition of 1% sodium dodecyl sulfate (SDS); both forms were active and could transit to each other by incubating in or removing SDS. The enzyme belongs to carbohydrate esterase family 7 and had a double specificity on both the acetylated oligosaccharide and cephalosporin C (CPC) and 7-aminocephalosporanic acid (7-ACA). The activity of this purified enzyme toward CPC and 7-ACA was highest among all the acetyl xylan esterase from CE family 7, which were 484 and 888 U/mg, respectively, and endowed itself with great industrial interest on semi-synthetic ?-lactam antibiotics. The optimum pH of the purified enzyme was 8.0, and the optimum temperature was 50 C, and the enzyme had high thermal stability, broad range of pH tolerance, and extremely organic solvent tolerance. PMID:23828600

  2. Trends of Antibiotic Consumption in Korea According to National Reimbursement Data (2008–2012)

    PubMed Central

    Yoon, Young Kyung; Park, Gi Chan; An, Hyonggin; Chun, Byung Chul; Sohn, Jang Wook; Kim, Min Ja

    2015-01-01

    Abstract This study determined the trends in the quantities and patterns of nationwide antibiotic consumption in the Republic of Korea (ROK). This nationwide descriptive epidemiological study was conducted in the ROK between 2008 and 2012. The quantities and patterns of total systemic antibiotic prescriptions were analyzed using National Health Insurance claims data collected through the Health Insurance Review and Assessment service. Data concerning systemic antibiotics were collected using measurement units of the defined daily dose (DDD) per 1000 people per day according to the Anatomical Therapeutic Chemical classification. Over the 5-year study period, the annual consumption of systemic antibiotics ranged from 21.68 to 23.12 DDD per 1000 people per day. Outpatient antibiotic use accounted for 80.9% of total consumption. A regression model with autoregressive errors showed significant increased consumption of major antibiotic subgroups, including 3rd-generation cephalosporins, carbapenems, and glycopeptides (P < 0.001). However, the antibiotic use of 1st- (P = 0.003), 2nd- (P = 0.004), and 3rd-generation (P = 0.018) cephalosporins among patients who underwent surgery under monitoring by the antimicrobial stewardship programs for perioperative prescription was significantly lower than in those who underwent surgery without monitoring programs. In time-series analysis, total antibiotic consumption demonstrated significant seasonality (P < 0.001). The consumption of broad-spectrum antibiotics was noted to have increased in the ROK from 2008 to 2012, providing a possible explanation for the changing epidemiology of multidrug resistance. Larger prospective studies are needed to investigate the impact on public health of monitoring programs of perioperative antibiotic usage. PMID:26579825

  3. ?-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis

    PubMed Central

    Gaudelli, Nicole M.; Long, Darcie H.; Townsend, Craig A.

    2014-01-01

    Non-ribosomal peptide synthetases (NRPSs) are giant enzymes comprised of modules that house repeated sets of functional domains, which select, activate and couple amino acids drawn from a pool of nearly 500 potential building blocks.1 The structurally and stereochemically diverse peptides generated in this manner underlie the biosynthesis of a large sector of natural products. Many of their derived metabolites are bioactive such as the antibiotics vancomycin, bacitracin, daptomycin and the ?-lactam-containing penicillins, cephalosporins and nocardicins. Although penicillins and cephalosporins are synthesised from a classically derived NRPS tripeptide (from ACVS, ?-(L-?-aminoadipyl)L-cysteinylD-valine synthetase)2, we now report an unprecedented NRPS activity to both assemble a serine-containing peptide and mediate its cyclisation to the critical ?-lactam ring of the nocardicin family of antibiotics. A histidine-rich condensation (C) domain, which typically carries out peptide bond formation during product assembly, was found to also synthesise the embedded 4-membered ring. Here, a mechanism is proposed and supporting experiments are described, which is distinct from the pathways that have evolved to the three other ?-lactam antibiotic families: penicillin/cephalosporins, clavams and carbapenems. These findings raise the possibility that ?-lactam rings can be regio- and stereospecifically integrated into engineered peptides for application as, for example, targeted protease inactivators.3,4 PMID:25624104

  4. Systematic analysis of the relationship between antibiotic use and extended-spectrum beta-lactamase resistance in Enterobacteriaceae in a French hospital: a time series analysis.

    PubMed

    Vibet, M-A; Roux, J; Montassier, E; Corvec, S; Juvin, M-E; Ngohou, C; Lepelletier, D; Batard, E

    2015-10-01

    The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on extended-spectrum beta-lactamase (ESBL) resistance among Enterobacteriaceae is poorly known. Our objective was to explore the association between ESBL and hospital use of various classes of antibacterial agents. The relationship between monthly use of 19 classes of antibacterial agents and incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital was studied between 2007 and 2013. Five antibiotic classes were significantly and independently associated with ESBL resistance. Uses of tetracyclines (link estimate ± SE, 0.0066 ± 0.0033), lincosamides (0.0093 ± 0.0029), and other antibacterial agents (0.0050 ± 0.0023) were associated with an increased incidence, while nitrofurantoin (-0.0188 ± 0.0062) and ticarcillin and piperacillin with or without enzyme inhibitor (-0.0078 ± 0.0031) were associated with a decreased incidence. In a multivariate model including 3rd- and 4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin-clavulanate, 3rd- and 4th-generation cephalosporins (0.0019 ± 0.0009) and fluoroquinolones (0.0020 ± 0.0008) were associated with an increased ESBL resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital use of tetracyclines and lincosamides may promote ESBL resistance in Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or without enzyme inhibitor should be considered as potential alternatives to broad-spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL resistance. PMID:26205663

  5. Study of the Electrophoretic Behavior of Cephalosporins by Capillary Zone Electrophoresis

    PubMed Central

    Hancu, Gabriel; Sasebe?i, Adina; Rusu, Aura; Kelemen, Hajnal; Ciurba, Adriana

    2015-01-01

    Purpose: The aim of the study was the characterization of the electrophoretic behavior of cephalosporins from different generation having different structural characteristics in order to develop a rapid, simple and efficient capillary electrophoretic method for their identification and simultaneous separation from complex mixtures. Methods: Ten cephalosporin derivatives (cefaclor, cefadroxil, cefalexin, cefazolin, cefoxitin, cefuroxime, cefoperazone, cefotaxime, ceftazidime, ceftriaxone) were analyzed by capillary zone electrophoresis using different background electrolyte solutions at different pH values. Electrophoretic mobilities of the analytes were calculated, the influence of the electrophoretic parameteres on the separation was established and the analytical conditions were optimized. Results: Taking into consideration their structural and chemical properties cephalosporins can be detected over a pH range between 6 and 10. The best results were obtained using a buffer solution containing 25 mM disodium hydrogenophosphate - 25 mM sodium dihydrogenophosphate, at a pH 7.00, + 25 kV voltage at a temperature of 25 C, UV detection at 210 nm. Using the optimized analytical conditions we achieved the simultaneous baseline separation for seven cephalosporins in less then 10 minutes. Conclusion: Using the described optimized electrophoretic procedures, capillary electrophoresis can be used for the identification and determination of cephalosporins in formulated pharmaceutical products and for their separation from complex mixtures. PMID:26236661

  6. National Practice in Antibiotic Prophylaxis in Breast Cancer Surgery

    PubMed Central

    Eroglu, Aydan; Karasoy, Durdu; Kurt, Halil; Baskan, Semih

    2014-01-01

    Background Although breast cancer surgery is regarded as a “clean” surgery, surgical site infection (SSI) rates are higher than expected. There is no consensus regarding the use of antibiotic prophylaxis in elective breast surgery. The nationwide survey was conducted to determine the trend of antibiotic prophylaxis in breast cancer among Turkish surgeons. Methods The survey was sent to surgeons who are member of Turkish Surgical Association (TSA) via e-mail from TSA web address. A 15 item web-based survey consisted of surgeon demographics and the use of prophylactic antibiotic in patients with risk factors related to SSI. Results The number of completed questionnaires was 245. The most common antibiotic used was first generation of cephalosporins. A majority of respondents indicated that prophylaxis was preferred in patients with high risk of SSI including preoperative chemotherapy or radiotherapy, older age, diabetes mellitus, immunodeficiency, immediate reconstruction (P < 0.05). However, the use of drain did not significantly influence antibiotic prophylaxis (P = 0.091). Conclusions The use of prophylactic antibiotic was strongly dependent on the presence of some risk factors; however, the variation in current practice regarding antibiotic prophylaxis demonstrated a lack of its effect on preventing SSI after breast cancer surgery. PMID:24400029

  7. Urine from Treated Cattle Drives Selection for Cephalosporin Resistant Escherichia coli in Soil

    PubMed Central

    Subbiah, Murugan; Shah, Devendra H.; Besser, Thomas E.; Ullman, Jeffrey L.; Call, Douglas R.

    2012-01-01

    The U.S. Food and Drug Administration recently issued new rules for using ceftiofur in food animals in part because of an increasing prevalence of enteric bacteria that are resistant to 3rd-generation cephalosporins. Parenteral ceftiofur treatment, however, has limited effects on enteric bacteria so we tested the hypothesis that excreted ceftiofur metabolites exert significant selection pressure for ceftiofur-resistant Escherichia coli in soil. Test matrices were prepared by mixing soil with bovine feces and adding urine containing ceftiofur metabolites (CFM) (0 ppm, ?50 ppm and ?100 ppm). Matrices were incubated at 23C or 4C for variable periods of time after which residual CFM was quantified using a bioassay. BlaCMY-2 plasmid-bearing ceftiofur resistant (cefR) E. coli and one-month old calves were used to study the selection effects of CFM and transmission of cefR bacteria from the environment back to animals. Our studies showed that urinary CFM (?13 ppm final concentration) is biologically degraded in soil within 2.7 days at 23C, but persists up to 23.3 days at 4C. Even short-term persistence in soil provides a >1 log10 advantage to resistant E. coli populations, resulting in significantly prolonged persistence of these bacteria in the soil (?two months). We further show that resistant strains readily colonize calves by contact with contaminated bedding and without antibiotic selection pressure. Ceftiofur metabolites in urine amplify resistant E. coli populations and, if applicable to field conditions, this effect is far more compelling than reported selection in vivo after parenteral administration of ceftiofur. Because ceftiofur degradation is temperature dependent, these compounds may accumulate during colder months and this could further enhance selection as seasonal temperatures increase. If cost-effective engineered solutions can be developed to limit ex vivo selection, this may limit proliferation for ceftiofur resistant enteric bacteria while preserving the ability to use this important antibiotic in food animal production. PMID:23145021

  8. Trends of Antibiotic Consumption in Korea According to National Reimbursement Data (2008-2012): A Population-Based Epidemiologic Study.

    PubMed

    Yoon, Young Kyung; Park, Gi Chan; An, Hyonggin; Chun, Byung Chul; Sohn, Jang Wook; Kim, Min Ja

    2015-11-01

    This study determined the trends in the quantities and patterns of nationwide antibiotic consumption in the Republic of Korea (ROK).This nationwide descriptive epidemiological study was conducted in the ROK between 2008 and 2012. The quantities and patterns of total systemic antibiotic prescriptions were analyzed using National Health Insurance claims data collected through the Health Insurance Review and Assessment service. Data concerning systemic antibiotics were collected using measurement units of the defined daily dose (DDD) per 1000 people per day according to the Anatomical Therapeutic Chemical classification.Over the 5-year study period, the annual consumption of systemic antibiotics ranged from 21.68 to 23.12 DDD per 1000 people per day. Outpatient antibiotic use accounted for 80.9% of total consumption. A regression model with autoregressive errors showed significant increased consumption of major antibiotic subgroups, including 3rd-generation cephalosporins, carbapenems, and glycopeptides (P?antibiotic use of 1st- (P?=?0.003), 2nd- (P?=?0.004), and 3rd-generation (P?=?0.018) cephalosporins among patients who underwent surgery under monitoring by the antimicrobial stewardship programs for perioperative prescription was significantly lower than in those who underwent surgery without monitoring programs. In time-series analysis, total antibiotic consumption demonstrated significant seasonality (P?antibiotics was noted to have increased in the ROK from 2008 to 2012, providing a possible explanation for the changing epidemiology of multidrug resistance. Larger prospective studies are needed to investigate the impact on public health of monitoring programs of perioperative antibiotic usage. PMID:26579825

  9. Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy

    PubMed Central

    Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

  10. Antibiotic prophylaxis in Oral and Maxillofacial Surgery.

    PubMed

    Salmern-Escobar, Jose Ignacio; del Amo-Fernndez de Velasco, Alvaro

    2006-05-01

    Antibiotic prophylaxis in oral and maxillofacial surgery aims the prevention of the infection of the surgical wound, either due to the characteristics of the surgery or the general state of the patient. This risk increases with the contamination of the surgical operation area, making it necessary to imply a prophylactic treatment of the infection in clean-contaminated and contaminated surgeries and treatment of the infection in dirty surgeries. Moreover, a proper surgical technique helps to reduce the development of the postsurgical infection. The elective antibiotic chemotherapy ranges from penicillin-derivates with betalactamase inhibitors (amoxycillin-clavulanate, ampicilin-sulbactam) to second or third generation cephalosporins, quinolones or clindamycin. The indication for the use of these antibiotics depends on the type of surgery in oral and maxillofacial surgery, according to the degree of contamination. Thus in oral surgery and surgery of the salivary glands the literature demonstrates that there is not a better prognosis when using prophylactic antibiotherapy instead of not using it in healthy patients. In traumatology this prophylaxis is justified in compound fractures and those communicating with paranasal sinuses. En orthognatic surgery there is disagreement according to the criteria of using antibiotic prophylaxis, but short term treatment is preferred in case of using it. In oncological surgery it has been demonstrated the reduce in incidence of postsurgical infection using prophylactic peroperative antibiotherapy, mostly in those cases in which oral mucosa and cervical area contact. PMID:16648771

  11. The initial state of the human gut microbiome determines its reshaping by antibiotics.

    PubMed

    Raymond, Frdric; Ouameur, Amin A; Draspe, Maxime; Iqbal, Naeem; Gingras, Hlne; Dridi, Bdis; Leprohon, Philippe; Plante, Pier-Luc; Giroux, Richard; Brub, ve; Frenette, Johanne; Boudreau, Dominique K; Simard, Jean-Luc; Chabot, Isabelle; Domingo, Marc-Christian; Trottier, Sylvie; Boissinot, Maurice; Huletsky, Ann; Roy, Paul H; Ouellette, Marc; Bergeron, Michel G; Corbeil, Jacques

    2016-03-01

    Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments. PMID:26359913

  12. Use of ammonium molybdate in the colorimetric assay of cephalosporins.

    PubMed

    Abdel-K Halek, M M; Mahrous, M S

    1984-08-01

    A colorimetric method for the determination of five cephalosporins (cefoxitin sodium, cefotaxime sodium, cephapirin sodium, cephalothin sodium and cephaloridine), based on the blue colour formed by reaction of the cephalosporins with ammonium molybdate, is described. The effects of reagent concentration and reaction conditions are discussed. The proposed method has been applied to the analysis of cephalosporin injections, the results of which are in good agreement with those obtained by the official method of the British Pharmacopoeia. PMID:18963668

  13. Ceftaroline fosamil: A super-cephalosporin?

    PubMed

    Ghamrawi, Riane J; Neuner, Elizabeth; Rehm, Susan J

    2015-07-01

    Ceftaroline is a broad-spectrum cephalosporin used to treat infections caused by a variety of microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. However, it is not active against Pseudomonas aeruginosa, Bacteroides fragilis, and carbapenem-resistant Enterobacteriaceae. Its approved indications include community-acquired bacterial pneumonia and bacterial infections of skin and skin structures. It has also been used off-label to treat osteomyelitis, endocarditis, and meningitis caused by ceftaroline-susceptible organisms. PMID:26185943

  14. Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side Chains.

    PubMed

    Lee, Sang Hee; Kim, Mi Hyun; Lee, Kwangha; Jo, Eun Jung; Park, Hye Kyung

    2015-09-01

    Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins. PMID:25749765

  15. Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae

    PubMed Central

    Qin, Xuan; Oron, Assaf P.; Adler, Amanda L.; Wolter, Daniel J.; Berry, Jessica E.; Hoffman, Lucas; Weissman, Scott J.

    2014-01-01

    The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred. PMID:24798269

  16. Strategic alliance between the infectious diseases specialist and intensive care unit physician for change in antibiotic use.

    PubMed

    Curcio, D; Belloni, R

    2005-02-01

    There is a general consensus that antimicrobial use in intensive care units (ICU) is greater than that in general wards. By implementing a strategy of systematic infectious disease consultations in agreement with the ICU chief, we have modified the antibiotic prescription habits of the ICU physician. A reduction was observed in the use of selected antibiotics (third-generation cephalosporins, vancomycin, carbapenems and piperacillin-tazobactam), with a significant reduction in the length of hospital stay for ICU patients and lower antibiotic costs without negative impact on patient mortality. Leadership by the infectious diseases consultant in combination with commitment by ICU physicians is a simple and effective method to change antibiotic prescription habits in the ICU. PMID:15828447

  17. Novel Metagenome-Derived Carboxylesterase That Hydrolyzes ?-Lactam Antibiotics?

    PubMed Central

    Jeon, Jeong Ho; Kim, Soo-Jin; Lee, Hyun Sook; Cha, Sun-Shin; Lee, Jung Hun; Yoon, Sang-Hong; Koo, Bon-Sung; Lee, Chang-Muk; Choi, Sang Ho; Lee, Sang Hee; Kang, Sung Gyun; Lee, Jung-Hyun

    2011-01-01

    It has been proposed that family VIII carboxylesterases and class C ?-lactamases are phylogenetically related; however, none of carboxylesterases has been reported to hydrolyze ?-lactam antibiotics except nitrocefin, a nonclinical chromogenic substrate. Here, we describe the first example of a novel carboxylesterase derived from a metagenome that is able to cleave the amide bond of various ?-lactam substrates and the ester bond of p-nitrophenyl esters. A clone with lipolytic activity was selected by functional screening of a metagenomic library using tributyrin agar plates. The sequence analysis of the clone revealed the presence of an open reading frame (estU1) encoding a polypeptide of 426 amino acids, retaining an S-X-X-K motif that is conserved in class C ?-lactamases and family VIII carboxylesterases. The gene was overexpressed in Escherichia coli, and the purified recombinant protein (EstU1) was further characterized. EstU1 showed esterase activity toward various chromogenic p-nitrophenyl esters. In addition, it exhibited hydrolytic activity toward nitrocefin, leading us to investigate whether EstU1 could hydrolyze ?-lactam antibiotics. EstU1 was able to hydrolyze first-generation ?-lactam antibiotics, such as cephalosporins, cephaloridine, cephalothin, and cefazolin. In a kinetic study, EstU1 showed a similar range of substrate affinities for both p-nitrophenyl butyrate and first-generation cephalosporins while the turnover efficiency for the latter was much lower. Furthermore, site-directed mutagenesis studies revealed that the catalytic triad of EstU1 plays a crucial role in hydrolyzing both ester bonds of p-nitrophenyl esters and amide bonds of the ?-lactam ring of antibiotics, implicating the predicted catalytic triad of EstU1 in both activities. PMID:21908637

  18. Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action

    PubMed Central

    2012-01-01

    Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833

  19. The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics.

    PubMed

    Krawczyk-Balska, A; Markiewicz, Z

    2016-02-01

    Intrinsic resistance to antibiotics is a serious therapeutic problem in the case of many bacterial species. The Gram-positive human pathogen Listeria monocytogenes is intrinsically resistant to broad spectrum cephalosporin antibiotics, which are commonly used in therapy of bacterial infections. Besides three penicillin-binding proteins the intrinsic cephalosporin resistome of L.monocytogenes includes multidrug resistance transporter transporters, proteins involved in peptidoglycan biosynthesis and modification, cell envelope proteins with structural or general detoxification function, cytoplasmic proteins with unknown function and regulatory proteins. Analysis of the regulation of the expression of genes involved in the intrinsic resistance of L.monocytogenes to cephalosporins highlights the high complexity of control of the intrinsic resistance phenotype. The regulation of the transcription of the intrinsic resistome determinants involves the activity of eight regulators, namely LisR, CesR, LiaR, VirR, ?(B) , ?(H) , ?(L) and PrfA, of which the most prominent role play LisR, CesR and ?(B) . Furthermore, the vast majority of the intrinsic resistome determinants contribute to the tolerance of different stress conditions and virulence. A study indicates that O-acetyltransferase OatA is the most promising candidate for co-drug development since an agent targeting OatA should sensitize L.monocytogenes to certain antibiotics, therefore improving the efficacy of listeriosis treatment as well as food preservation measures. PMID:26509460

  20. A Point Prevalence Survey of Antibiotic Use in 18 Hospitals in Egypt

    PubMed Central

    Talaat, Maha; Saied, Tamer; Kandeel, Amr; Abo El-Ata, Gehad A.; El-Kholy, Amani; Hafez, Soad; Osman, Ashraf; Abdel Razik, Mohamed; Ismail, Ghada; El-Masry, Sherine; Galal, Rami; Yehia, Mohamad; Amer, Amira; Calfee, David P.

    2014-01-01

    Inappropriate antibiotic use leads to increased risk of antibiotic resistance and other adverse outcomes. The objectives of the study were to determine the prevalence and characteristics of antibiotic use in Egyptian hospitals to identify opportunities for quality improvement. A point prevalence survey was conducted in 18 hospitals in March 2011. A total of 3408 patients were included and 59% received at least one antibiotic, with the most significant use among persons <12 years and intensive care unit patients (p < 0.05). Third generation cephalosporin were the most commonly prescribed antibiotics (28.7% of prescriptions). Reasons for antibiotic use included treatment of community—(27%) and healthcare-associated infections (11%) and surgical (39%) and medical (23%) prophylaxis. Among surgical prophylaxis recipients, only 28% of evaluable cases received the first dose within two hours before incision and only 25% of cases received surgical prophylaxis for <24 h. The prevalence of antibiotic use in Egyptian hospitals was high with obvious targets for antimicrobial stewardship activities including provision of antibiotic prescription guidelines and optimization of surgical and medical prophylaxis practices.

  1. Magnetic separation of antibiotics by electrochemical magnetic seeding

    NASA Astrophysics Data System (ADS)

    Ihara, I.; Toyoda, K.; Beneragama, N.; Umetsu, K.

    2009-03-01

    Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

  2. Characterization and antibiotic susceptibility of Listeria monocytogenes isolated from poultry and red meat in Morocco

    PubMed Central

    Ennaji, Hayat; Timinouni, Mohammed; Ennaji, My Mustapha; Hassar, Mohammed; Cohen, Nozha

    2008-01-01

    This study was carried out on 426 samples of raw meats collected from butcheries and supermarkets in Casablanca, Morocco. The samples were examined for the occurrence of Listeria species. Strains of Listeria monocytogenes were characterized by several biochemical tests and confirmed by polymerase chain reaction (PCR). β-hemolytic cultures and nonhemolytic isolates were tested for biochemical properties with the Listeria API test. Among the 43 Listeria species isolates; we identified 10 strains for L. monocytogenes (23.3%), 31 strains for L. innocua (72.1%) and 2 strains for L. welshimeri (4.6%). Strains of L. monocytogenes were separated by multiplex PCR; two serogroups IIb and IVb were thus differentiated. Antibiotic susceptibility of L. monocytogenes to 21 antibiotics was determined by the disk diffusion method. All isolates were susceptible to a wide range of the tested antibiotics with the exception of nalidixic acid, colistine and cephalosporins second and third generation for which they were all resistant. PMID:21694879

  3. [Emerging and important antibiotic resistance in Gram negative bacteria: epidemiology, theory and practice].

    PubMed

    Nordmann, P; Poirel, L

    2014-04-23

    Emerging and clinically-relevant antibiotic resistance mechanisms among Gram-negative rods are the extended-spectrum beta-lactamases (ESBL), carbapenemases, and 16S RNA methylases conferring resistance to aminoglycosides. Those resistance determinants do confer multiresistance to antibiotics. They are found in Enterobacteriaceae (especially community-acquired isolates, Pseudomonas aeruginosa and Acinetobacter baumannii). Detection of ESBL-producing and carbapenemase-producing isolates rely on the use of rapid diagnostic techniques that have to be performed when a reduced susceptibility to 3rd/4th generation cephalosporins or to carbapenems is observed, respectively. Only an early detection of those emerging resistance traits may contribute to limit their nosocomial spread and to optimize the antibiotic stewardship. PMID:24843986

  4. Multiresistant bacterial infections in liver cirrhosis: Clinical impact and new empirical antibiotic treatment policies

    PubMed Central

    Acevedo, Juan

    2015-01-01

    Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment (third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications. PMID:25954474

  5. Kounis syndrome secondary to intravenous cephalosporin administration

    PubMed Central

    Venkateswararao, Sunkavalli; Rajendiran, Gopalan; Sundaram, Rathakrishnan Shanmuga; Mounika, Godavarthi

    2015-01-01

    Kounis syndrome is a clinical condition due to hypersensitivity that culminates into acute coronary syndrome (ACS) which can be fatal. A 36-year-old male with no conventional coronary risk factors presented elsewhere with a history of fever for 4 days, cough with expectoration, diarrhea and was treated with cephalosporin (Inj. Cefotaxime as an infusion) along with analgesics. He experienced generalized itching 5 minutes after cefotaxime infusion followed by sweating, headache, chest pain with facial and periorbital swelling for which he was rushed to our hospital. On examination he was afebrile with a low blood pressure. Electrocardiogram taken at an outside hospital revealed incomplete right bundle branch block and ST depression V3V5. Investigations showed increase in troponin T. He was managed with anti-histamines and standard protocol for treatment of ACS. Coronary angiogram revealed normal coronaries. The patient improved symptomatically with treatment and was discharged on an anti-platelet, nitrate and a statin.

  6. The effect of monitoring of antibiotic use on decreasing antibiotic resistance in the hospital.

    PubMed

    Giamarellou, H; Antoniadou, A

    1997-01-01

    In Greece, antibiotic over-consumption and high resistance rates run in parallel. In the spring of 1989 surveillance of 12500 Gram-negative strains, derived from 55 hospitals from all over Greece, revealed that resistance rates of Pseudomonas aeruginosa, Enterobacter spp., Klebsiella spp. and Acinetobacter spp. to antimicrobial agents introduced after 1985 exceeded 50%. As a consequence, the application of (1) rules of hospital hygiene, (2) educational small group programs, and (3) an antibiotic policy aiming to restrict antibiotic use, was decided in Laiko General Hospital. Since 1989, imipenem, the newer quinolones, vancomycin, aztreonam and third-generation cephalosporins were only ordered to the hospital pharmacy after completion of a specific request form, which since 1991 has been more detailed and which can be signed only by physicians with interest in infectious diseases. In 1991, in cooperation with the pharmacy, an audit program was added requiring a final inspection of the already approved request forms by an infectious diseases specialist. Any disagreement was discussed with the physicians in charge. Consumption data were analysed monthly and discussed with each department. Newer antibiotic consumption in a selected month (November) of three consecutive years, before (1991) and after the application of the audit program (1992-1995) has been analysed. Results reveal a decrease in consumption of restricted antibiotics, especially in surgical departments and in kidney transplantation units, without simultaneous increase in consumption of the non-restricted compounds. Since 1994, resistance has decreased remarkably. However, the resistance of quinolones is increasing steeply. Consequently, for the last 12 months quinolones have been removed from the hospital formulary. An audit program requires close co-operation of physicians, pharmacists and, particularly, of surgeons, in the application of a correct prophylaxis regimen. It seems to be efficacious in reducing both resistance rates and total antibiotic consumption. PMID:9189636

  7. Prospective Randomized Study for Antibiotic Prophylaxis in Spine Surgery: Choice of Drug, Dosage, and Timing

    PubMed Central

    Kailash, Kannan Karthick; Vijayraghavan, P.V.

    2013-01-01

    Study Design Prospective randomized study of antibiotic prophylaxis in elective spine surgery. Purpose The aim of this study was to compare the rate of postoperative surgical site infection for a single dose of two different generations of cephalosporin with different dosage and timing of the antibiotics. Overview of Literature Current recommendation for prophylaxis in elective spine surgery is up to 60 minutes prior to incision. No study has investigated between different generation of cephalosporin for prophylaxis in elective spine surgery with respect to choice, dosage and timing. Methods This study was a prospective randomized study of 90 patients, assessed for the occurrence of surgical site infection (defined by the Centers for Disease Control and Prevention criteria) and other infections for up to 6 months after surgery. Demographic, surgical and further data were collected on subsequent operations, including hardware removal. Results Mean age in our group was 47 years (range, 19-71 years). The male to female ratio was 49:41 and the average timing of administration of antibiotics was 77 minutes (range, 30-120 minutes). The average blood loss was 626 mL (range, 150-3,000 mL) with a mean duration of surgery for 3.2 hours (range, 1.5-6 hours). One case of superficial infection and one case of deep infection met the exclusion criteria. Conclusions Our results support the use of a single preoperative dose of antibiotics in instrumented and non-instrumented elective spine surgery up to one hour prior to incision. There was no difference in terms of occurrence of surgical site infection with respect to dosage, choice and timing of antibiotics. PMID:24066215

  8. The use of cephalosporins for gonorrhea: The impending problem of resistance

    PubMed Central

    Barry, Pennan M.; Klausner, Jeffrey D.

    2009-01-01

    Gonorrhea remains an important clinical and public health problem throughout the world. Gonococcal infections have historically been diagnosed by Gram stain and culture, but are increasingly diagnosed through nucleic acid tests thereby eliminating the opportunity for antimicrobial susceptibility testing. Gonococcal infections are typically treated with single-dose therapy with an agent found to cure >95% of cases. Unfortunately, the gonococcus has repeatedly developed resistance to antimicrobials including sulfonamides, penicillin, tetracyclines, and fluoroquinolones. This has left third-generation cephalosporins as the lone class of antimicrobials currently recommended as first line therapy for gonorrhea in some regions. However, resistance to oral third-generation cephalosporins has emerged and spread in Asia, Australia and elsewhere. The mechanism of this resistance seems to be associated with a mosaic penicillin binding protein (penA) in addition to other chromosomal mutations previously found to confer resistance to beta-lactam antimicrobials (ponA, mtrR, penB, pilQ). Few good options exist or are in development for treating cephalosporin resistant isolates as most have had multidrug resistance. Preventing the spread of resistant isolates will depend on ambitious antimicrobial management programs, strengthening and expanding surveillance networks, and through effective sexually transmitted disease control and prevention. PMID:19284360

  9. Swine flu and antibiotics.

    PubMed

    Barlow, Gavin D

    2009-11-01

    Health services worldwide are likely to be hard-pressed by swine flu-related illness in the months ahead. Secondary infections with Streptococcus pneumoniae, other streptococci (e.g. Streptococcus pyogenes), Haemophilus influenzae and Staphylococcus aureus are likely to be important causes of morbidity and mortality. The UK Department of Health recently published clinical pathways for the management of swine flu. Suggested severity criteria have not been validated in respiratory infection and are different from those previously published. Antibiotics are recommended for all patients assessed at hospital, regardless of severity of illness; cephalosporins or quinolones are suggested for inpatients with pneumonia. These recommendations will jeopardize recent decreases in Clostridium difficile-associated diarrhoea (CDAD) and methicillin-resistant S. aureus (MRSA) in UK hospitals. This article, written on behalf of the BSAC Council, considers these recommendations and provides alternative antibiotic regimens for a range of clinical scenarios. PMID:19740909

  10. Surveillance of Antibiotic Consumption Using the Focus of Infection Approach in 2 Hospitals in Ujjain, India

    PubMed Central

    Pathak, Ashish; Mahadik, Kalpana; Dhaneria, Surya Prakesh; Sharma, Ashish; Eriksson, Bo; Lundborg, Cecilia Stlsby

    2012-01-01

    Antibiotic surveillance initiatives are limited in resource-constrained settings. In the present study, a quantitative comparison of antibiotic use rates for suspected infections in 2 hospitals in India was performed using the focus of infection approach to identify targets for quality improvement in antibiotic prescription patterns in hospitalized patients. Methods This observational study was carried out in one teaching and one nonteaching hospital. All the patients with suspected bacterial etiology were included. Data on the prescribed antibiotics and the focus of infection were prospectively collected using a structured questionnaire. Each diagnosis was further reviewed and confirmed by an independent consultant. The prescribed antibiotics were coded according to the World Health Organization Anatomic Therapeutic Classification (ATC) index with the defined daily dose (DDD) methodology. Focus-specific DDDs were calculated per hundred patient days (DDD/HPD). Results A total of 6026 patients were included from 72 participating physicians out of available 75 physicians. Overall antibiotic prescribing was higher by 5 percentage points in the teaching hospital (95%) than in the nonteaching hospital (90%). Quinolones (ciprofloxacin constituting 86% of DDD/HPD) were the highest prescribed class in the teaching hospital, and third-generation cephalosporins (with ceftriaxone and ceftriaxone/sulbactam constituting 40% and 28% of the DDD/HPD, respectively), in the nonteaching hospital. The targets identified for improvement were the following: longer than recommended duration of prophylaxis and lack of distinction between prophylaxis and therapy among surgical patients; irrational antibiotic prescribing in gastroenteritis; overuse of quinolones and lack of use of penicillin in pneumonia; overuse of quinolones and lack of use of doxycycline and macrolides in genital infections; and overreliance on antibiotics for treating skin and soft tissue infections. Conclusions Providing a quantitative comparison of antibiotic use rates for suspected infections, using the focus of infection approach along with the ATC/DDD methodology, appears appropriate for identifying targets for quality improvement with regards to antibiotic prescribing. PMID:22715402

  11. Gentamicin Nephrotoxicity: Failure of Three Cephalosporins to Potentiate Injury in Rats

    PubMed Central

    Harrison, William O.; Silverblatt, Fredric J.; Turck, Marvin

    1975-01-01

    The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone. Images PMID:1180545

  12. Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis

    PubMed Central

    2013-01-01

    Objective Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia. Methods This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed. Results The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n = 7, 71%–100%), other Klebsiella species (n = 7, 28%–80%), and Staphylococcus (n = 36, 25%–40%). Conclusions The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance. PMID:24764539

  13. The environmental release and fate of antibiotics.

    PubMed

    Manzetti, Sergio; Ghisi, Rossella

    2014-02-15

    Antibiotics have been used as medical remedies for over 50 years and have recently emerged as new pollutants in the environment. This review encompasses the fate of several antibiotics in the environment, including sulfonamides, nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the cycle of transfer from humans and animals including their metabolic transformation. The results show that antibiotic metabolites are of considerable persistence and are localized to ground-water and drinking water supplies. Furthermore, the results also show that several phases of the cycle of antibiotics in the environment are not well understood, such as how low concentrations of antibiotic metabolites in the diet affect humans and animals. This review also shows that improved wastewater decontamination processes are remediating factors for these emerging pollutants. The results obtained here may help legislators and authorities in understanding the fate and transformation of antibiotics in the environment. PMID:24456854

  14. Pharmacological aspects of the antibiotics used for urological diagnostic procedures.

    PubMed

    Mazzei, Teresita; Diacciati, Sara

    2014-10-01

    Surgical antimicrobial prophylaxis is the use of an antibiotic before, during, or shortly after a urological procedure to prevent postoperative infections such as urinary tract or wound infection. The optimal antimicrobial drug must be microbiologically active against the most frequent potential pathogens and have good pharmacological properties. Correct timing of antimicrobial prophylaxis is the first critical issue in determining treatment efficacy. The antibiotic must be administered before the start of the surgical procedure in order to ensure a high tissue level at the time of microbial contamination. If using an oral antibiotic, this must be administered 1-3 hours before the operation and a parenteral antibiotic should be administered at the induction of anaesthesia. The antibiotics potentially useful for antimicrobial prophylaxis are the beta-lactams, cotrimoxazole, fluoroquinolones, and fosfomycin trometamol. The criteria for choosing the optimal antibiotic include an appropriate antimicrobial spectrum, favourable pharmacokinetic parameters (especially good tissue penetration), and elevated safety or tolerability. The use of cotrimoxazole must be restricted due to increasing chemoresistance. Unfortunately fluoroquinolone-based regimens, once the mainstay of prophylaxis guidelines, are increasingly ineffective due to a constant increase in multidrug-resistant (MDR) Gram-negative bacteria. The same concerns apply with regard to the second and third generation cephalosporins that have problems of resistance and, if administered orally, do not sufficiently penetrate prostatic tissue. An appropriate beta-lactam could be an aminopenicillin combined with a beta-lactamase inhibitor. Fosfomycin trometamol can also be a good potential choice due to its elevated activity against MDR Gram-negative bacteria and its favourable pharmacokinetic parameters, including an elevated penetration into prostatic tissue. PMID:25245708

  15. Structural Bases for Stability-Function Tradeoffs in Antibiotic Resistance

    PubMed Central

    Thomas, Veena L.; McReynolds, Andrea C.; Shoichet, Brian K.

    2009-01-01

    Pre-organization of enzyme active sites for substrate recognition typically comes at a cost to the stability of the folded form of the protein, and consequently enzymes can be dramatically stabilized by substitutions that attenuate the size and pre-organization strain of the active site. How this stability-activity trade-off constrains enzyme evolution has remained less certain, and it is unclear whether one should expect major stability insults as enzymes mutate towards new activities, or how these new activities manifest structurally. These questions are both germane and easy to study in ?-lactamases, which are evolving on the timescale of years to confer resistance to an ever-broader spectrum of ?-lactam antibiotics. To explore whether stability is a substantial constraint on this antibiotic resistance evolution, we investigated extended-spectrum mutants of class C ?-lactamases which had evolved new activity versus third-generation cephalosporins. Five mutant enzymes had between 100- to 200-fold increased activity against the antibiotic cefotaxime in enzyme assays, and the mutant enzymes all lost thermodynamic stability from 1.7 to 4.1 kcal/mol consistent with the function-stability hypothesis. Intriguingly, several of the substitutions were 10 20 from the catalytic serine; the question arose how they conferred extended-spectrum activity. Eight structures, including complexes with inhibitors and extended-spectrum antibiotics, were determined by x-ray crystallography. Distinct mechanisms of action are revealed for each mutant, including changes in the flexibility and ground state structures of the enzyme. These results explain the structural bases for the antibiotic resistance conferred by these substitutions, and their corresponding decrease in protein stability, which will constrain the evolution of new antibiotic resistance. PMID:19913034

  16. Antibiotic prescribing in two private sector hospitals; one teaching and one non-teaching: A cross-sectional study in Ujjain, India

    PubMed Central

    2012-01-01

    Background The worldwide increase in antibiotic resistant bacteria is of great concern. One of the main causes is antibiotic use which is likely to be high but is poorly described in India. The aim was to analyze and compare antibiotic prescribing for inpatients, in two private sector tertiary care hospitals; one Teaching and one Non-teaching, in Ujjain, India. Methods A cross-sectional study with manual data collection was carried out in 2008. Antibiotic prescribing was recorded for all inpatients throughout their hospital stay. Demographic profile of inpatients and prescribed antibiotics were compared. WHO Anatomical Therapeutic Chemical (ATC) classifications for antibiotics was used and Defined Daily Doses (DDD) were calculated per patient day. Results A total of 8385 inpatients were admitted during the study period. In the Teaching hospital (TH) 82% of 3004 and in the Non-teaching hospital (NTH) 79% of 5381 patients were prescribed antibiotics. The most commonly prescribed antibiotic groups were; fluoroquinolones and aminoglycosides in the TH and, 3rd generation cephalosporins and combination of antibiotics in the NTH. Of the prescriptions, 51% in the TH and 87% in the NTH (p<0.001) were for parenteral route administration. Prescribing by trade name was higher in the NTH (96%) compared with the TH (63%, p<0.001). Conclusions The results from both hospitals show extensive antibiotic prescribing. High use of combinations of antibiotics in the NTH might indicate pressure from pharmaceutical companies. There is a need to formulate and implement; based on local prescribing and resistance data; contextually appropriate antibiotic prescribing guidelines and a local antibiotic stewardship program. PMID:22788873

  17. Bacteriology and antibiotic resistance pattern in community acquired urinary tract infection.

    PubMed

    Sharan, Rajiv; Kumar, Dhananjay; Mukherjee, B

    2013-07-01

    Extensive use of antibiotics have resulted in development of resistance among most commonly used drugs in community acquired urinary tract infection (UTI). This study was conducted to identify the resistance pattern in community acquired UTI .We collected urine for routine examination and culture from suprapubic urine in all the cases to avoid any contamination. E. Coli was the most common organism identified. Among oral antibiotics, there was high degree of resistance to penicillin group and cephalosporin groups. Among parentral antibiotics, all the cephalosporins were variably resistant except cephaperazone-salbactum. PMID:23942441

  18. Antibiotic Prescribing among Pediatric Inpatients with Potential Infections in Two Private Sector Hospitals in Central India

    PubMed Central

    Pathak, Ashish; Stlsby Lundborg, Cecilia

    2015-01-01

    Introduction Infectious diseases are one of the major causes of child mortality in India. Pediatric patients are commonly prescribed antibiotics for non-bacterial infections. Monitoring of local antibiotic prescribing with respect to the diagnosis is necessary to improve the prescribing practices. The aim of the study was to describe antibiotic prescribing for potential infections among patients admitted in pediatric departments in two private sector hospitals; one teaching (TH) and one non-teaching (NTH) in Central India. Methods Data from all patients admitted at the pediatric departments of both study hospitals was collected manually, for 3 years (20082011) using a customized form. Data from inpatients aged 018 years, diagnosed with; acute gastroenteritis (AGE), respiratory tract infections, enteric fever, viral fever or unspecified fever were focused for analysis. Antibiotic prescriptions were analysed using the WHO Anatomical Therapeutic Chemical (ATC) classification system and defined daily doses (DDDs). Adherence to the Indian Academy of Pediatrics list of essential medicines (IAP-LEM) was investigated. P-values <0.05 were considered significant. Results Oftotal6, 825 inpatients admitted at two pediatric departments, 510 patients from the TH and 2,479from the NTH were selected based on the assigned potential infectious diagnoses. Of these, 224 patients (44%) at the TH and 2,088 (84%) at the NTH were prescribed at least one antibiotic during hospital stay (odds ratio-0.69, 95%confidence interval-0.52 to 0.93; p<0.001). Patients with AGE, viral- and enteric fever were frequently prescribed antibiotics at both hospitals, yet higher proportion were prescribed antibiotics at the NTH compared to the TH. Broad-spectrum antibiotics were the most commonly prescribed antibiotic class in both hospitals, namely third generation cephalosporins, J01DD (69%) at the TH, and new fixed dose combinations of antibiotics J01R (FDCs, 42%) at the NTH. At the TH, 37% of the antibiotic prescriptions were comprised of antibiotics listed in the IAP-LEM, compared to 24% at the NTH (p<0.05). Conclusions Broad-spectrum antibiotics were prescribed frequently in both hospitals also for the un-indicated conditions such as viral fever and enteric fever. At the NTH, new FDCs were more frequently prescribed and adherence to the IAP-LEM was substantially lower at the NTH compared to the TH. The results demonstrate need to develop diagnosis-specific prescribing guidelines to facilitate rational use of antibiotics and implement antibiotic stewardship program. PMID:26540104

  19. Recovery of cephalosporin-resistant Escherichia coli and Salmonella from pork, beef and chicken marketed in Nova Scotia

    PubMed Central

    Forward, Kevin R; Matheson, Katherine M; Hiltz, Margot; Musgrave, Heather; Poppe, Cornelius

    2004-01-01

    BACKGROUND: Antimicrobial use in farm animals is a potentially important contributor to the emergence of antimicrobial resistance. Resistant Salmonella may lead to serious human infections and resistant Escherichia coli may transfer plasmid-encoded resistance genes to other pathogens. OBJECTIVE: To determine the prevalence of E coli and Salmonella species resistant to the third generation of cephalosporins in retail meat products in Halifax, Nova Scotia in 2002. METHODS: Ground beef, ground pork and chicken wings were tested for E coli and Salmonella. E coli were selected on ceftriaxonecontaining media. Beta-lactamases were characterised by isoelectric focusing, polymerase chain reaction and sequencing. Pulsed field gel electrophoresis was performed to determine the relationship of strains. The transferability of plasmids and location of resistance genes was also determined. RESULTS: Forty-three of 75 packages of chicken wings contained ceftriaxone-resistant E coli; 42 of these contained beta-lactamases with isoelectric points at approximately 8.7. Six of seven CMY primer amplicons that were sequenced contained plasmid-mediated Citrobacter freundii-derived blaCMY-2; the other contained a CMY-2- like beta-lactamase. Pulsed field gel electrophoresis patterns demonstrated that strains were not clonal in nature. Four chicken samples contained Salmonella, one of which contained bla CMY-2-mediated resistance and an E coli bearing the same gene, but on different plasmids. Four of 100 beef samples contained blaCMY-2-bearing E coli; none contained Salmonella. Two of 75 pork samples contained ceftriaxone resistant E coli, one of which encoded for CMY-2. One susceptible Salmonella strain was recovered from pork. CONCLUSIONS: Chicken from retail outlets located in Halifax, Nova Scotia, commonly contained blaCMY-2-bearing E coli. The relationship antibiotics used in food-producing animals and its effect on resistance of commensals and pathogens needs to be determined. PMID:18159497

  20. Salmonella bacteraemia in Pokhara: emergence of antibiotic resistance.

    PubMed

    Guha, Simantee; Jalan, Basavaraj Yogitha; Dey, Sangeeta; Easow, Joshy Maducolil; Wilson, Godwin; Shivananda, Padavagadu Ganapati

    2005-06-01

    We undertook a retrospective hospital based study of 2,354 blood culture specimens from June 2000 to May 2003 in order to determine the isolation rates of Salmonella species and their antibiotic susceptibility patterns in western Nepal. Blood samples were cultured and identification of Salmonella species. and their antibiotic susceptibility testing were done as per standard protocol. Of the total 114 (4.8 %) yielded Salmonella species. Of them 76 (66.7%) Salmonella typhi and 38 (33.3%) S. paratyphi A. S. typhi was found to be the predominant species each year. Higher proportion of Salmonella bacteraemia was seen in adults, with a clearcut male to female preponderance (1.8:1). Monsoons enhanced the risk of acquiring enteric fever. There is also a rise in the number of multi-drug resistant strains in and around Pokhara Valley, with 40.7% S. typhi and 5.2% S. paratyphi A showing resistance to two or more antibiotics. These isolates were primarily resistant to the first line drugs namely Ampicillin, Chloramphenicol and Cotrimoxazole but susceptible to third generation Cephalosporins. Appearance of multi drug resistance poses considerable threat of increased morbidity and mortality in this region. This emphasizes the need for prudent use of antimicrobials. PMID:16295716

  1. The role of prophylactic antibiotics on surgical site infection in elective laparoscopic cholecystectomy

    PubMed Central

    Chong, Jae Uk; Lim, Jin Hong; Kim, Jee Ye; Kim, Sung Hoon

    2015-01-01

    Backgrounds/Aims Although laparoscopic cholecystectomy is a common and widely accepted technique, the use of prophylactic antibiotics in elective laparoscopic cholecystectomy still remains controversial. The aim of this study is to determine whether prophylactic antibiotics could prevent surgical site infection after elective laparoscopic cholecystectomy and to identify any risk factors for surgical site infection. Methods This study included 471 patients undergoing laparoscopic cholecystectomy between January 2009 and May 2012. Period 1 patients (279) received second generation cephalosporin 1 g intravenously after induction of anesthesia, and Period 2 patients (192) were not given prophylactic antibiotics. The characteristics and surgical site infections of the patients were compared and analyzed. Results The overall rate of surgical site infection was 1.69% for the total of 471 patients. The incidence of surgical site infection was similar for the two Periods: 5 of 279 patients (1.79%) in Period 1, 3 of 192 patients (1.56%) in Period 2 (p=0.973). All of the patients with surgical site infections were well treated under conservative treatments without any sequelae. The preoperative albumin level (p=0.023) contributed to surgical site infection. Conclusions Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy but patients in poor nutritional state with low albumin level should consider prophylactic antibiotics. PMID:26693239

  2. Non-heme iron oxygenases generate natural structural diversity in carbapenem antibiotics.

    PubMed

    Bodner, Micah J; Phelan, Ryan M; Freeman, Michael F; Li, Rongfeng; Townsend, Craig A

    2010-01-13

    Carbapenems are a clinically important antibiotic family. More than 50 naturally occurring carbapenam/ems are known and are distinguished primarily by their C-2/C-6 side chains where many are only differentiated by the oxidation states of these substituents. With a limited palette of variations the carbapenem family comprises a natural combinatorial library, and C-2/C-6 oxidation is associated with increased efficacy. We demonstrate that ThnG and ThnQ encoded by the thienamycin gene cluster in Streptomyces cattleya oxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 (5) giving N-acetyl thienamycin (2). ThnG catalyzes sequential desaturation and sulfoxidation of PS-5 (5), giving PS-7 (7) and its sulfoxide (9). The enzymes are relatively substrate selective but are proposed to give rise to the oxidative diversity of carbapenems produced by S. cattleya, and orthologues likely function similarly in allied streptomyces. Elucidating the roles of ThnG and ThnQ will focus further investigations of carbapenem antibiotic biosynthesis. PMID:20017478

  3. Antibiotic Resistance

    MedlinePLUS

    ... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

  4. Animal and Human Multidrug-Resistant, Cephalosporin-Resistant Salmonella Isolates Expressing a Plasmid-Mediated CMY-2 AmpC ?-Lactamase

    PubMed Central

    Winokur, P. L.; Brueggemann, A.; DeSalvo, D. L.; Hoffmann, L.; Apley, M. D.; Uhlenhopp, E. K.; Pfaller, M. A.; Doern, G. V.

    2000-01-01

    Salmonella spp. are important food-borne pathogens that are demonstrating increasing antimicrobial resistance rates in isolates obtained from food animals and humans. In this study, 10 multidrug-resistant, cephalosporin-resistant Salmonella isolates from bovine, porcine, and human sources from a single geographic region were identified. All isolates demonstrated resistance to cephamycins and extended-spectrum cephalosporins as well as tetracycline, chloramphenicol, streptomycin, and sulfisoxazole. Molecular epidemiological analyses revealed eight distinct chromosomal DNA patterns, suggesting that clonal spread could not entirely explain the distribution of this antimicrobial resistance phenotype. However, all isolates encoded an AmpC-like ?-lactamase, CMY-2. Eight isolates contained a large nonconjugative plasmid that could transform Escherichia coli. Transformants coexpressed cephalosporin, tetracycline, chloramphenicol, streptomycin, and sulfisoxazole resistances. Plasmid DNA revealed highly related restriction fragments though plasmids appeared to have undergone some evolution over time. Multidrug-resistant, cephalosporin-resistant Salmonella spp. present significant therapeutic problems in animal and human health care and raise further questions about the association between antimicrobial resistance, antibiotic use in animals, and transfer of multidrug-resistant Salmonella spp. between animals and man. PMID:10991860

  5. Enhancing the Antibiotic Antibacterial Effect by Sub Lethal Tellurite Concentrations: Tellurite and Cefotaxime Act Synergistically in Escherichia coli

    PubMed Central

    Molina-Quiroz, Roberto C.; Muoz-Villagrn, Claudia M.; de la Torre, Erick; Tantalen, Juan C.; Vsquez, Claudio C.; Prez-Donoso, Jos M.

    2012-01-01

    The emergence of antibiotic-resistant pathogenic bacteria during the last decades has become a public health concern worldwide. Aiming to explore new alternatives to treat antibiotic-resistant bacteria and given that the tellurium oxyanion tellurite is highly toxic for most microorganisms, we evaluated the ability of sub lethal tellurite concentrations to strengthen the effect of several antibiotics. Tellurite, at nM or M concentrations, increased importantly the toxicity of defined antibacterials. This was observed with both Gram negative and Gram positive bacteria, irrespective of the antibiotic or tellurite tolerance of the particular microorganism. The tellurite-mediated antibiotic-potentiating effect occurs in laboratory and clinical, uropathogenic Escherichia coli, especially with antibiotics disturbing the cell wall (ampicillin, cefotaxime) or protein synthesis (tetracycline, chloramphenicol, gentamicin). In particular, the effect of tellurite on the activity of the clinically-relevant, third-generation cephalosporin (cefotaxime), was evaluated. Cell viability assays showed that tellurite and cefotaxime act synergistically against E. coli. In conclusion, using tellurite like an adjuvant could be of great help to cope with several multi-resistant pathogens. PMID:22536386

  6. Resistance of uropathogenic bacteria to first-line antibiotics in mexico city: A multicenter susceptibility analysis

    PubMed Central

    Arredondo-Garca, Jos Luis; Soriano-Becerril, Diana; Solrzano-Santos, Fortino; Arbo-Sosa, Antonio; Coria-Jimnez, Rafael; Arzate-Barbosa, Patricia

    2007-01-01

    Abstract Background Growing antibiotic resistance demands the constant reassessment of antimicrobial efficacy, particularly in countries with wide antibiotic abuse, where higher resistance prevalence is often found. Knowledge of resistance trends is particularly important when prescribing antibiotics empirically, as is usually the case for urinary tract infections (UTIs). Currently, in Mexico City, ampicillin, cotrimoxazole (trimethoprim/sulfamethoxazole), and ciprofloxacin are used as first-line antibiotic treatment for UTI. Objective The aim of this study was to analyze the resistance of bacterial isolates to antibiotics, with a focus on first-line antibiotics, in Mexican pediatric patients and sexually active or pregnant female outpatients. Methods In this multicenter susceptibility analysis, bacterial isolates from urine samples collected from pediatric patients and sexually-active or pregnant female outpatients presenting with acute, uncomplicated UTIs in Mexico City from January 2006 through June 2006, were included in the study. Samples were tested for susceptibility to 10 antibiotics by the disk-diffusion method. Results Four-hundred and seventeen bacterial isolates were derived from sexually active or pregnant female outpatients (324 Escherichia coli) and pediatric patients (93 Klebsiella pneumoniae). We found a high prevalence of resistance towards the drugs used as first-line when treating UTIs: ampicillin, cotrimoxazole, and ciprofloxacin (79%, 60%, and 24% resistance, respectively). Ninety-eight percent of K pneumoniae isolates were resistant to ampicillin, whereas 66% of the E coli isolates were resistant to cotrimoxazole. Resistance towards third-generation cephalosporins was also high (6%8% of E coli and 10%28% of K pneumoniae). This was possibly caused by chromosomal ?-lactamases, as 30% of all isolates were also resistant to amoxicillin/clavulanate. In contrast, 98% of the E coli isolates and 84% of the K pneumoniae strains (96% of all isolates) were found to be susceptible to nitrofurantoin, which has been in clinical use for much longer than most other drugs in this study. Conclusion In these urine samples from laboratories in Mexico City, resistance of K pneumoniae and E coli isolates to first-line treatment (ampicillin, cotrimoxazole, or ciprofloxacin) of UTI was high, whereas most E coli and K pneumoniae isolates were susceptible to nitrofurantoin and the fourth-generation cephalosporin cefepime. (Curr Ther Res Clin Exp. 2007;68:120126) Copyright 2007 Excerpta Medica, Inc. PMID:24678125

  7. Expedient antibiotics production: Final report

    SciTech Connect

    Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

    1988-05-01

    The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented. This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.

  8. Aspects of the Mechanism of Action of Some Cephalosporins

    PubMed Central

    Russell, A. D.; Fountain, R. H.

    1971-01-01

    Cephaloridine and cephalexin had no effect on ribonucleic acid (RNA), deoxyribonucleic acid (DNA), or protein synthesis in Escherichia coli. However, cephalosporin 7/30 [7-(S-benzylthioacetamido)-cephem-3-ylmethyl-N -dimethyldithiocarbamate-4-carboxylic acid] and dimethyldithiocarbamate (DMDT), which occupies the side chain at position 3 in the 7/30 molecule, inhibited protein synthesis (and, to a lesser extent, RNA and DNA syntheses) in E. coli and had an inhibitory effect on the growth of Saccharomyces carlsbergensis. A bioautograph technique showed that two inhibitory spots were obtained with 7/30 but only one such spot with cephaloridine. Release of DMDT onto or in the bacterial cell may be responsible for unusual mode of action of cephalosporin 7/30. PMID:4928017

  9. Structure-based prediction of modifications in glutarylamidase to allow single-step enzymatic production of 7-aminocephalosporanic acid from cephalosporin C.

    PubMed

    Fritz-Wolf, Karin; Koller, Klaus-Peter; Lange, Gudrun; Liesum, Alexander; Sauber, Klaus; Schreuder, Herman; Aretz, Werner; Kabsch, Wolfgang

    2002-01-01

    Glutarylamidase is an important enzyme employed in the commercial production of 7-aminocephalosporanic acid, a starting compound in the synthesis of cephalosporin antibiotics. 7-aminocephalosporanic acid is obtained from cephalosporin C, a natural antibiotic, either chemically or by a two-step enzymatic process utilizing the enzymes D-amino acid oxidase and glutarylamidase. We have investigated possibilities for redesigning glutarylamidase for the production of 7-aminocephalosporanic acid from cephalosporin C in a single enzymatic step. These studies are based on the structures of glutarylamidase, which we have solved with bound phosphate and ethylene glycol to 2.5 A resolution and with bound glycerol to 2.4 A. The phosphate binds near the catalytic serine in a way that mimics the hemiacetal that develops during catalysis, while the glycerol occupies the side-chain binding pocket. Our structures show that the enzyme is not only structurally similar to penicillin G acylase but also employs essentially the same mechanism in which the alpha-amino group of the catalytic serine acts as a base. A subtle difference is the presence of two catalytic dyads, His B23/Glu B455 and His B23/Ser B1, that are not seen in penicillin G acylase. In contrast to classical serine proteases, the central histidine of these dyads interacts indirectly with the O(gamma) through a hydrogen bond relay network involving the alpha-amino group of the serine and a bound water molecule. A plausible model of the enzyme-substrate complex is proposed that leads to the prediction of mutants of glutarylamidase that should enable the enzyme to deacylate cephalosporin C into 7-aminocephalosporanic acid. PMID:11742126

  10. A comparison of antibiotic regimens in the treatment of acute melioidosis in a mouse model.

    PubMed

    Ulett, Glen C; Hirst, Robert; Bowden, Bruce; Powell, Kellie; Norton, Robert

    2003-01-01

    Melioidosis is caused by the Gram-negative bacillus Burkholderia pseudomallei. Most clinical reports of disease are from south-east Asia and northern Australia. The organism is intrinsically resistant to most commonly available antibiotics. Standard therapy includes ceftazidime either alone or in combination with co-trimoxazole. The clinical advantage in adding co-trimoxazole has never been determined; nor has the activity of newer, fourth-generation cephalosporins, such as cefepime, been studied in the treatment of this condition. BALB/c mice have been shown to represent an animal model of melioidosis. This animal model was used in this study to compare the efficacy of ceftazidime and cefepime alone or with co-trimoxazole, in the therapy of melioidosis. Antibiotic levels in the mice were determined by HPLC, and dosing was modified to keep plasma antibiotic levels at or above the MIC for the organism-antibiotic combination for a significant part of a 12 h period. Bacterial load, as determined by splenic counts, showed that ceftazidime in combination with co-trimoxazole was the most effective therapeutic option. The animal model described in this study can be used as a preliminary evaluation of therapeutic options for melioidosis. PMID:12493790

  11. Short-duration, single-agent antibiotic prophylaxis for meningitis in trans-sphenoidal surgery.

    PubMed

    Little, Andrew S; White, William L

    2011-12-01

    Perioperative bacterial meningitis after trans-sphenoidal surgery for pituitary and parasellar lesions is an uncommon but serious complication. Little evidence guides the choice of chemoprophylaxis in this setting. To begin to address this deficiency, we investigated the incidence of perioperative meningitis in 442 patients who underwent trans-sphenoidal surgery and received a short chemoprophylaxis regimen with a single agent and did not require lumbar drainage. In 2005 we instituted a standardized antibiotic prophylaxis protocol for trans-sphenoidal surgery that utilized intravenous cefuroxime, a second-generation cephalosporin with broad coverage and excellent spinal fluid penetration, administered 30 min before surgery and 8 h later. The primary endpoint was the incidence of perioperative (within 30 days of surgery) bacterial meningitis. Data from The Barrow Pituitary Outcomes Project, a prospectively maintained patient research database, were supplemented with review of medical records and hospital discharge codes. There were no cases of perioperative meningitis. Three patients developed delayed meningitis associated with persistent or recurrent spinal fluid leakage 2-8 months after surgery. Perioperatively, seven patients received additional antibiotics for urinary tract infections. A single-agent, short-duration chemoprophylaxis regimen for trans-sphenoidal surgery is effective at preventing perioperative meningitis in patients who do not require lumbar drainage after surgery. The results of this regimen compare favorably to historical rates achieved with longer regimens that use two antibiotics. Future studies will investigate the role prophylactic antibiotics play in nasal mucosa healing and sinusitis. PMID:21347665

  12. Emergence of integron borne PER-1 mediated extended spectrum cephalosporin resistance among nosocomial isolates of Gram-negative bacilli

    PubMed Central

    Maurya, Anand Prakash; Choudhury, Debarati; Talukdar, Anupam Das; Dhar (Chanda), Debadatta; Chakravarty, Atanu; Bhattacharjee, Amitabha

    2015-01-01

    Background & objectives: Pseudomonas extended resistant (PER) enzymes are rare type of extended-spectrum beta lactamases (ESBLs) that confer third generation cephalosporin resistance. These are often integron borne and laterally transmitted. The aim of the present study was to investigate the emergence of integron borne cephalosporin resistant PER-1 gene in diverse incompatibility (Inc) group plasmids among Gram-negative bacteria. Methods: A total of 613 consecutive, non-duplicate, Gram-negative bacteria of Enterobacteriaceae family and non-fermenting Gram-negative bacteria were isolated from different clinical specimens during a period of 18 months. For amplification and detection of blaPER, multiplex PCR was done. For understanding the genetic environment of blaPER-1, integrase gene PCR and cassette PCR (59 be) was performed. Gene transferability experiment was carried out and PCR based replicon typing was performed for incompatibility group typing of plasmids using 18 pairs of primers. An inhibitor based method was used for phenotypic detection of intrinsic resistance. Results: Multiplex PCR and sequencing confirmed that 45 isolates were harbouring blaPER-1. Both class 1 and class 2 integrons were observed among them. Integrase and cassette PCR (59 be) PCR results confirmed that the resistant determinant was located within class 1 integron. Transformation and conjugation experiments revealed that PER-1 was laterally transferable and disseminated through diverse Inc plasmid type. Efflux pump mediated carbapenem resistance was observed in all isolates. All isolates belonged to heterogenous groups. Interpretation & conclusions: This study demonstrates the dissemination of cephalosporins resistant, integron borne blaPER-1 in hospital setting in this part of the country and emphasizes on the rational use of third generation cephalosporins to slow down the expansion of this rare type of ESBL gene. PMID:26205025

  13. Impact of 2011 French guidelines on antibiotic prescription for acute otitis media in infants.

    TOXLINE Toxicology Bibliographic Information

    Levy C; Pereira M; Guedj R; Abt-Nord C; Gelbert NB; Cohen R; Alberti C; Gajdos V; Angoulvant F

    2014-03-01

    OBJECTIVE: In 2011, new guidelines on antibiotic prescription for acute otitis media (AOM) were published in France to decrease the use of third generation cephalosporins that promote the carriage of extended-spectrum beta-lactamase producing Escherichia coli. Our objective was to assess the impact of the 2011 French recommendations on the type of antibiotics prescribed for AOM.METHODS: Fourteen thousand six hundred and sixty-one children, 6 to 24 months of age, presenting with AOM were included in 2 studies, between November 1, 2009 and October 31, 2012. The first one was conducted with the support of 62 private practice pediatricians; the second one was conducted in 7 pediatric emergency departments. Three periods of 1 year each were defined.RESULTS: Antibiotics were prescribed in 12,471 (85.1%) of cases of AOM during the study period. Amoxicillin prescriptions was multiplied by 25, between the first year (2.6%) and the last year (66.1%). Conversely, prescriptions of cefpodoxime proxetil and amoxicillin-clavulanic acid decreased from 33.6% and 62.0% in the first year to 5.2% and 27.7% in the last year, respectively. This trend was observed in both private practices and in the pediatric emergency departments.CONCLUSION: Amoxicillin became the most frequently prescribed antibiotic for AOM in 2012, complying with the 2011 French guidelines, while the proportion of prescribed broad-spectrum antibiotics decreased. Our study highlights the importance of guidelines to decrease the prescription of broad-spectrum antibiotics, a crucial factor in the prevention of antibiotic resistance.

  14. Antibiotic Resistance

    MedlinePLUS

    ... For Consumers Consumer Information by Audience For Women Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... these products really help. To Learn More about Antibiotic Resistance Get Smart About Antibiotics (Video) Fact Sheets and ...

  15. Antibiotic Safety

    MedlinePLUS

    ... Copyright © 2005 by The Association for Professionals in Infection Control and Epidemiology (APIC). www.apic.org Antibiotic Safety What are Antibiotics? Antibiotics are powerful medicines that help stop bacterial infections. They are used to kill germs that cause ...

  16. Lipophilicity study of eight cephalosporins by reversed-phase thin-layer chromatographic method.

    PubMed

    D?browska, Monika; Komsta, ?ukasz; Krzek, Jan; Kokoszka, Kinga

    2015-11-01

    The lipophilicity (R(M0)) and specific hydrophobic surface area for the representatives of four generation cephalosporins have been determined by reversed-phase thin-layer chromatography, and the effect of different mobile-phase modifiers (such as methanol, acetonitrile, acetone, 1,4-dioxane and 2-propanol) on the retention has been studied. The compounds studied showed typical retention behavior; their R(M) values decreased linearly with increasing concentration of the organic modifier in the eluent. The linear correlations between the volume fraction of the organic solvent and the R(M) values over a limited range were established for each solute, resulting in high values of correlation coefficients (>0.95 in most cases). R(M) values were determined by various concentrations of organic modifier, and the correlation obtained was extrapolated to 0% of organic modifier. Chromatographically established logP (R(M0)) parameters were compared with computationally calculated partition coefficients values (AClogP, ALOGP, KOWWIN, ALOGPs, XLOGP2, MLOGP and XLOGP3) and experimental octanol-water logP values (measured by the shake flask method). The received results demonstrate that RP-TLC may be a good alternative technique for analytics in describing the lipophilic nature of investigated cephalosporins as well as the activity. PMID:25990503

  17. Escherichia coli resistant to cephalosporins and quinolones is still susceptible to the cephalosporin-quinolone ester Ro 23-9424.

    PubMed Central

    Pace, J; Bertasso, A; Georgopapadakou, N H

    1991-01-01

    Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cephalosporin (desacetylcefotaxime) linked through an ester bond to a fluoroquinolone (fleroxacin). Its activity against mutants of Escherichia coli TE18 resistant to both antibacterial components was examined. E. coli TE18 overproduces the AmpC beta-lactamase and is resistant to several cephalosporins, including desacetylcefotaxime (MIC, 50 micrograms/ml), although it is still susceptible to Ro 23-9424 (MIC, 0.2 microgram/ml). Thirty-five spontaneous, two-step mutants of E. coli TE18 which were resistant to fleroxacin (MIC, 50 micrograms/ml) were isolated. In the mutants, replicative DNA biosynthesis (permeabilized cells) was resistant to fleroxacin, and some mutants had porin abnormalities. However, all remained susceptible to Ro 23-9424 (MIC, 0.5 microgram/ml). Examination of beta-lactamase activity in the parent strain revealed that it hydrolyzes desacetylcefotaxime more rapidly than it does Ro 23-9424. Thus, Ro 23-9424 may be less susceptible to the gram-negative, chromosomal beta-lactamases that hydrolyze several broad-spectrum cephalosporins and may be effective in cases in which neither of its two components is active. Images PMID:1649574

  18. New antibiotics for bad bugs: where are we?

    PubMed Central

    2013-01-01

    Bacterial resistance to antibiotics is growing up day by day in both community and hospital setting, with a significant impact on the mortality and morbidity rates and the financial burden that is associated. In the last two decades multi drug resistant microorganisms (both hospital- and community-acquired) challenged the scientific groups into developing new antimicrobial compounds that can provide safety in use according to the new regulation, good efficacy patterns, and low resistance profile. In this review we made an evaluation of present data regarding the new classes and the new molecules from already existing classes of antibiotics and the ongoing trends in antimicrobial development. Infectious Diseases Society of America (IDSA) supported a proGram, called “the ′10 × ´20′ initiative”, to develop ten new systemic antibacterial drugs within 2020. The microorganisms mainly involved in the resistance process, so called the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) were the main targets. In the era of antimicrobial resistance the new antimicrobial agents like fifth generation cephalosporins, carbapenems, monobactams, β-lactamases inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines active against Gram-positive pathogens, like vancomycin-resistant S. aureus (VRSA) and MRSA, penicillin-resistant streptococci, and vancomycin resistant Enterococcus (VRE) but also against highly resistant Gram-negative organisms are more than welcome. Of these compounds some are already approved by official agencies, some are still in study, but the need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections. Therefore the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance. PMID:23984642

  19. Skin and skin structure infections: treatment with newer generation fluoroquinolones

    PubMed Central

    Giordano, Philip; Weber, Kurt; Gesin, Gail; Kubert, Jason

    2007-01-01

    Skin and skin structure infections (SSSI) are an emerging issue in healthcare. They are responsible for increasing heathcare utilization, both in hospitalizations and intravenous antibiotic use. SSSI are caused by an evolving variety of pathogens, including Gram-positive, Gram-negative, and anaerobic bacteria. In combination with mounting resistance patterns, this diverse range of bacteria mandate empiric broad-spectrum antibiotic coverage. Historically, cephalosporins and penicillins have been the mainstay of treatment, but recent data suggest newer generation fluoroquinolones are being used with increasing frequency. In 2005, moxifloxacin joined gatifloxacin and levofloxacin as newer generation fluoroquionolones with Food and Drug Administration indications for SSSIs. Even within this group there exist subtle differences that impact optimal management. This paper offers the clinician a comparative review of the antimicrobial spectrum, pharmacodynamics, pharmacokinetics, and clinical efficacy data to support the appropriate use of fluoroquinolones in SSSIs. PMID:18360639

  20. In Vitro Antimicrobial Activity of a Siderophore Cephalosporin, S-649266, against Enterobacteriaceae Clinical Isolates, Including Carbapenem-Resistant Strains.

    PubMed

    Kohira, Naoki; West, Joshua; Ito, Akinobu; Ito-Horiyama, Tsukasa; Nakamura, Rio; Sato, Takafumi; Rittenhouse, Stephen; Tsuji, Masakatsu; Yamano, Yoshinori

    2015-01-01

    S-649266 is a novel siderophore cephalosporin antibiotic with a catechol moiety on the 3-position side chain. Two sets of clinical isolate collections were used to evaluate the antimicrobial activity of S-649266 against Enterobacteriaceae. These sets included 617 global isolates collected between 2009 and 2011 and 233 ?-lactamase-identified isolates, including 47 KPC-, 49 NDM-, 12 VIM-, and 8 IMP-producers. The MIC90 values of S-649266 against the first set of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Enterobacter aerogenes, and Enterobacter cloacae isolates were all ?1 ?g/ml, and there were only 8 isolates (1.3%) among these 617 clinical isolates with MIC values of ?8 ?g/ml. In the second set, the MIC values of S-649266 were ?4 ?g/ml against 109 strains among 116 KPC-producing and class B (metallo) carbapenemase-producing strains. In addition, S-649266 showed MIC values of ?2 ?g/ml against each of the 13 strains that produced other types of carbapenemases such as SME, NMC, and OXA-48. The mechanisms of the decreased susceptibility of 7 class B carbapenemase-producing strains with MIC values of ?16 ?g/ml are uncertain. This is the first report to demonstrate that S-649266, a novel siderophore cephalosporin, has significant antimicrobial activity against Enterobacteriaceae, including strains that produce carbapenemases such as KPC and NDM-1. PMID:26574013

  1. Minimum requirements of hydrophobic and hydrophilic features in cationic peptide antibiotics (CPAs): pharmacophore generation and validation with cationic steroid antibiotics (CSAs).

    PubMed

    Sundriyal, Sandeep; Sharma, Rohit K; Jain, Rahul; Bharatam, Prasad V

    2008-04-01

    Cationic peptide antibiotics (CPAs) are known to possess amphiphilic structure, by virtue of which they display lytic activity against bacterial cell membranes. Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. Recent studies indicate that it is possible to decrease the chain-length of these peptides without loss of activity, and suggest that a minimum of two positive ionizable (hydrophilic) and two bulky groups (hydrophobic) are required for antimicrobial activity. By employing the HipHop module of the software package CATALYST, we have translated these experimental findings into 3-D pharmacophore models by finding common features among active peptides. Positively ionizable (PI) and hydrophobic (HYD) features are the important characteristics of compounds used for pharmacophore model development. Based on the highest score and the presence of amphiphilic structure, two separate hypothesis, Ec-2 and Sa-6 for Escherichia coli and Staphylococcus aureus, respectively, were selected for mapping analysis of active and inactive peptides against these organisms. The resulting models not only provided information on the minimum requirement of PI and HYD features but also indicated the importance of their relative arrangement in space. The minimum requirement for PI features was two in both cases but the number of HYD features required in the case of E. coli was four while for S. aureus it was found to be three. These hypotheses were able to differentiate between active and inactive CPAs against both organisms and were able to explain the experimental results. The hypotheses were further validated using cationic steroid antibiotics (CSAs), a different class of facial amphiphiles with same mechanism of antimicrobial action as that of CPAs. The results showed that CSAs also require similar minimum features to be active against both E. coli and S. aureus. These studies also indicate that the minimum feature requirements may be conserved for different strains of the same organism. Figure shows the mapping of an active cationic peptide antibiotic (CPA) mapped to the most acceptable hypothesis Sa6 against S. aureus. PMID:18270757

  2. Structural analysis and investigation of molecular properties of Cefpodoxime acid, a third generation antibiotic

    NASA Astrophysics Data System (ADS)

    Suganthi, S.; Balu, P.; Sathyanarayanamoorthi, V.; Kannappan, V.; Kamil, M. G. Mohamed; Kumar, R.

    2016-03-01

    Extensive quantum mechanical studies are carried out on Cefpodoxime acid (CA), a new generation drug by Hartree-Fock (HF) and B3LYP methods to understand the structural and spectral characteristics of the molecule. The most stable geometry of the molecule was optimized and the bond parameters were reported. The spectroscopic properties of this pharmaceutically important compound were investigated by FT-IR, FT-Raman, UV and 1H NMR techniques. The scaled vibrational frequencies of CA in the ground state are calculated by HF and B3LYP methods with 6-311++G (d, p) basis set and compared with the observed FT-IR and FT-Raman spectra. The vibrational spectral analysis indicates the presence of two intra molecular hydrogen bonds in the molecule which is supported by theoretical study. 1H NMR chemical shifts (δ) were calculated for the CA molecule and compared with the experimental values. The theoretical electronic absorption spectral data in water and ethanol solvents were computed by TD-DFT method. UV-Vis absorption spectra of CA are recorded in these two solvents and compared with theoretical spectra. The spectral data and natural bond orbital (NBO) analysis confirm the occurrence of intra molecular interactions in CA. The electronic distribution, in conjunction with electrophilicity index of CA was used to establish the active site and type of interaction between CA and beta lactamases. Mulliken population analysis on atomic charges is also carried out and thermodynamic properties of the title compound are calculated.

  3. Ceftolozane/Tazobactam: A Novel Cephalosporin/?-Lactamase Inhibitor Combination.

    PubMed

    Cho, Jonathan C; Fiorenza, Mallory A; Estrada, Sandy J

    2015-07-01

    Ceftolozane/tazobactam is a novel antipseudomonal ?-lactam/?-lactamase inhibitor combination that is currently approved by the United States Food and Drug Administration for the treatment of complicated intraabdominal infections (cIAI) and complicated urinary tract infections (cUTI). It exhibits bactericidal properties through inhibition of bacterial cell wall biosynthesis, which is mediated through penicillin-binding proteins (PBPs). Ceftolozane is a potent PBP3 inhibitor and has a higher affinity for PBP1b compared with other ?-lactam agents. Ceftolozane/tazobactam differs from other cephalosporins due to its increased activity against some AmpC ?-lactamases and Pseudomonas aeruginosa. The addition of tazobactam provides enhanced activity against extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae and certain anaerobic organisms. Population pharmacokinetic studies for ceftolozane and ceftolozane/tazobactam are best described by a two-compartment model with zero-order input and linear elimination. Similar to other cephalosporins, the best pharmacodynamic property to predict efficacy for ceftolozane/tazobactam is a concentration that remains above the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval. For Enterobacteriaceae and P. aeruginosa strains, the time above the MIC (T > MIC) needed to produce bactericidal activity was much less with ceftolozane than other cephalosporins, with T > MIC requirements of approximately 30%. For currently approved indications, the dose of ceftolozane/tazobactam is 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) intravenously every 8 hours given as a 1-hour infusion. Ceftolozane has low plasma protein binding (20%) and is predominantly excreted unchanged in the urine (? 92%). Dosage adjustments are required for moderate-to-severe renal impairment and in patients receiving hemodialysis. Based on data from clinical trials, adverse effects due to ceftolozane/tazobactam do not differ considerably from other cephalosporins, with the most common being nausea, diarrhea, headache, and pyrexia. Ceftolozane/tazobactam is a promising new agent for the treatment of cIAI and cUTI, including those caused by multidrug-resistant gram-negative organisms. PMID:26133315

  4. Cephalosporins to carbapenems: 1-oxygenated carbapenems and carbapenams.

    PubMed

    Rosati, R L; Kapili, L V; Morrissey, P; Retsema, J A

    1990-01-01

    The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corresponding carbapenem. The resulting 1-oxocarbapenems (2) were selectively transformed through reduction into 1-oxygenated carbapenems and carbapenams (3 and 4, respectively). On microbiological screening, a carbapenem (3c) was found to possess a broad spectrum of activity. An interesting antibacterial profile was discovered for a carbapenam (26). PMID:2404120

  5. Assessing the Contributions of the LiaS Histidine Kinase to the Innate Resistance of Listeria monocytogenes to Nisin, Cephalosporins, and Disinfectants

    PubMed Central

    Collins, Barry; Guinane, Caitriona M.; Ross, R. Paul

    2012-01-01

    The Listeria monocytogenes LiaSR two-component system (2CS) encoded by lmo1021 and lmo1022 plays an important role in resistance to the food preservative nisin. A nonpolar deletion in the histidine kinase-encoding component (ΔliaS) resulted in a 4-fold increase in nisin resistance. In contrast, the ΔliaS strain exhibited increased sensitivity to a number of cephalosporin antibiotics (and was also altered with respect to its response to a variety of other antimicrobials, including the active agents of a number of disinfectants). This pattern of increased nisin resistance and reduced cephalosporin resistance in L. monocytogenes has previously been associated with mutation of a second histidine kinase, LisK, which is a predicted regulator of liaS and a penicillin binding protein encoded by lmo2229. We noted that lmo2229 transcription is increased in the ΔliaS mutant and in a ΔliaS ΔlisK double mutant and that disruption of lmo2229 in the ΔliaS ΔlisK mutant resulted in a dramatic sensitization to nisin but had a relatively minor impact on cephalosporin resistance. We anticipate that further efforts to unravel the complex mechanisms by which LiaSR impacts on the antimicrobial resistance of L. monocytogenes could facilitate the development of strategies to increase the susceptibility of the pathogen to these agents. PMID:22327581

  6. New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.

    PubMed

    Elbashir, Abdalla A; Ahmed, Shazalia M Ali; Aboul-Enein, Hassan Y

    2012-05-01

    Simple, accurate and sensitive spectrofluorimetric method has been proposed for the determination of three cephalosporins, namely; cefixime (cefi), cephalexine (ceph), cefotaxime sodium (cefo) in pharmaceutical formulations. The method is based on a reaction between cephalosporins with 1, 2-naphthoquinone-4-sulfonic (NQS) in alkaline medium, at pH values of 12.0 for cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted with chloroform and subsequently measured at 600,580 and 580 nm after excitation at 520,455 and 490 nm for cefi, ceph and cefo respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over the concentrations of 10-35 ng/mL, 10-60 ng/mL and 20-45 ng/mL for cefi,ceph and cefo, respectively. The detection limits were 2.02 ng/mL, 2.09 ng/mL and 2.30 ng/mL for cefi, ceph and cefo, respectively, with a linear regression correlation coefficient of 0.9987, 0.9995 and 0.9991 and recoveries in range from 98.5-107.04, 95.17-101.00 and 95.00-109.55% for cefi, ceph and cefo, respectively. This method is simple and can be applied for the determination of cefi, ceph and cefo in pharmaceutical formulations in quality control laboratories. PMID:22160361

  7. New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.

    PubMed

    Ali Ahmed, Shazalia M; Elbashir, Abdalla A; Suliman, Fakhr Eldin O; Aboul-Enein, Hassan Y

    2013-01-01

    A simple, accurate, precise spectrofluorimetric method has been proposed for the determination of three cephalosporins, namely, cefixime (cefi), cephalexine (ceph), and cefotaxime sodium (cefo) in pharmaceutical formulations. This method is based on a reaction between cephalosporins with 8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt (HPTS) in alkaline medium, at pH 12.0 for cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted with chloroform and subsequent measurements of the formed fluorescent products at 520, 500 and 510 nm after excitation at 480, 470 and 480 nm for cefi, ceph and cefo respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over concentrations of 10-60 ng/mL, 5-35 ng/mL and 10-60 ng/mL for cefi, ceph and cefo, respectively. The detection limits were 4.20 ng/mL, 2.54 ng/mL and 4.09 ng/mL for cefi, ceph and cefo, respectively, with a linear regression correlation coefficient of 0.99783, 0.99705 and 0.9978 and recoveries in ranges 96.96-105.77, 96.13-102.55 and 95.45-105.39% for cefi, ceph and cefo, respectively. This method is simple and can be applied for the determination of cefi, ceph and cefo in pharmaceutical formulations in quality control laboratories. PMID:22991324

  8. Characteristics of ciprofloxacin and cephalosporin resistant Escherichia coli isolated from turkeys in Great Britain.

    PubMed

    Randall, L P; Mueller-Doblies, D; Lemma, F L; Horton, R A; Teale, C J; Davies, R H

    2013-01-01

    1. A field study was performed to investigate the presence and characteristics of ciprofloxacin-resistant, extended spectrum β-lactamase (ESBL) and AmpC Escherichia coli from turkeys in Great Britain. E. coli were isolated from ~9000 boot swab samples from 27 different farms owned by four different companies. Between 1 and 14 visits were made to each farm (mean 3) at between 0 and 15 m intervals (mean ~5 m). 2. CHROMagar ECC with and without ciprofloxacin or cephalosporin antibiotics was used as selective isolation media. Representative isolates with different phenotypes were tested for mutations in gyrA and for: qnrA, B, S, qepA and aac(6')-Ib genes, for ESBL phenotype, the presence of bla genes and plasmid type, and for ampC genes Representative ciprofloxacin-resistant and CTX-M isolates were further tested for serotype and PFGE type. On ciprofloxacin selective media 55% of samples yielded ciprofloxacin resistant E. coli and of those further analysed, most had ciprofloxacin MICs >4 mg/l and mutations in gyrA. 3. For the different companies, the mean number of samples per farm with cefoxitin- or cefotaxime-resistant isolates ranged from 1·0% to 61·9% and 4·7% to 31·7% respectively. Cefotaxime-resistance was most commonly associated with an ESBL phenotype, a CTX-M-1 or CTX-M-14 sequence type and an I1-γ or K plasmid inc type. The mechanism of cefoxitin resistance was not determined for most isolates, but where determined it was bla . 4. PFGE and serotyping showed clonally-related isolates persisting over multiple visits suggesting both more prudent use of antibiotics and improved farm hygiene are needed to address the issue of antimicrobial resistance in isolates from turkeys. PMID:23444859

  9. An Audit-Based, Infectious Disease Specialist-Guided Antimicrobial Stewardship Program Profoundly Reduced Antibiotic Use Without Negatively Affecting Patient Outcomes

    PubMed Central

    Nilholm, Hannah; Holmstrand, Linnea; Ahl, Jonas; Mnsson, Fredrik; Odenholt, Inga; Tham, Johan; Melander, Eva; Resman, Fredrik

    2015-01-01

    Background.?Antimicrobial stewardship programs are increasingly implemented in hospital care. They aim to simultaneously optimize outcomes for individual patients with infections and reduce financial and health-associated costs of overuse of antibiotics. Few studies have examined the effects of antimicrobial stewardship programs in settings with low proportions of antimicrobial resistance, such as in Sweden. Methods.?An antimicrobial stewardship program was introduced during 5 months of 2013 in a department of internal medicine in southern Sweden. The intervention consisted of audits twice weekly on all patients given antibiotic treatment. The intervention period was compared with a historical control consisting of patients treated with antibiotics in the same wards in 2012. Studied outcome variables included 28-day mortality and readmission, length of hospital stay, and use of antibiotics. Results.?A reduction of 27% in total antibiotic use (2387 days of any antibiotic) was observed in the intervention period compared with the control period. The reduction was due to fewer patients started on antibiotics as well as to significantly shorter durations of antibiotic courses (P < .001). An earlier switch to oral therapy and a specific reduction in use of third-generation cephalosporins and fluoroquinolones was also evident. Mortality, total readmissions, and lengths of stay in hospital were unchanged compared with the control period, whereas readmissions due to a nonresolved infection were fewer during the intervention of 2013. Conclusions.?This study demonstrates that an infectious disease specialist-guided antimicrobial stewardship program can profoundly reduce antibiotic use in a low-resistance setting with no negative effect on patient outcome. PMID:26380341

  10. Antibiotic resistance.

    PubMed

    Rambhia, Kunal J; Gronvall, Gigi Kwik

    2009-12-01

    Antibiotic resistance poses serious challenges to health and national security, and policy changes will be required to mitigate the consequences of antibiotic resistance. Resistance can arise in disease-causing bacteria naturally, or it can be deliberately introduced to a biological weapon. In either case, life-saving drugs are rendered ineffective. Resistant bacterial infections are difficult to treat, and there are few new antibiotics in the drug development pipeline. This article describes how antibiotic resistance affects health and national security, how bacteria become antibiotic resistant, and what should be done now so antibiotics will be available to save lives in the future. PMID:20028245

  11. Influence of substituent groups at the 3-position on the mass spectral fragmentation pathways of cephalosporins.

    PubMed

    Li, Jin; Zhang, Dou-sheng; Chong, Xiao-meng; Hu, Chang-qin

    2010-07-30

    The structural fragment ions of nine cephalosporins were studied by electrospray ionization quadrapole trap mass spectrometry (Q-Trap MS(n)) in positive mode. The influence of substituent groups in the 3-position on fragmentation pathway B, an alpha-cleavage between the C7-C8 single bond, coupled with a [2,4]-trans-Diels-Alder cleavage simultaneously within the six-membered heterocyclic ring, was also investigated. It was found that when the substituent groups were methyl, chloride, vinyl, or propenyl, fragmentations belonging to pathway B were detected; however, when the substituents were heteroatoms such as O, N, or S, pathway B fragmentation was not detected. This suggested that the [M-R(3)](+) ion, which was produced by the bond cleavage within the substituent group at the 3-position, had a key influence on fragmentation pathway B. This could be attributed to the strong electronegativity of the heteroatoms (O, N, S) that favors the production of the [M-R(3)](+) ion. Moreover, having the positive charge of the [M-R(3)](+) ion localized on the nitrogen atom in the 1-position changed the electron density distribution of the heterocyclic structure, which prohibits a [2,4]-reverse-Diels-Alder fragmentation and as a result fragmentation pathway B could not occur. The influence of the substituent group in the 3-position was determined by the intensity ratio (e/d) of ions produced by fragmentation pathway A, a [2,2]-trans-Diels-Alder cleavage within the quaternary lactam ring, including the breaking of the amide bond and the C6-C7 single bond (ion d), and fragmentation pathway B (ion e). The results indicate that the electronegativity of the substituent group was a key influencing factor of pathway B fragmentation intensity, because the intensity ratio (e/d) is higher for a chlorine atom, a vinyl, or a propenyl group than that of a methyl group. This study provided some theoretical basis for the identification of cephalosporin antibiotics and structural analysis of related substances in drugs. PMID:20552707

  12. Effects of β-Lactam Antibiotics and Fluoroquinolones on Human Gut Microbiota in Relation to Clostridium difficile Associated Diarrhea

    PubMed Central

    Heinsen, Femke Anouska; Knecht, Carolin; Schilhabel, Anke; Schmitz, Ruth A.; Zimmermann, Alexandra; dos Santos, Vitor Martins; Ferrer, Manuel; Rosenstiel, Philip C.; Schreiber, Stefan; Friedrichs, Anette K.; Ott, Stephan J.

    2014-01-01

    Clostridium difficile infections are an emerging health problem in the modern hospital environment. Severe alterations of the gut microbiome with loss of resistance to colonization against C. difficile are thought to be the major trigger, but there is no clear concept of how C. difficile infection evolves and which microbiological factors are involved. We sequenced 16S rRNA amplicons generated from DNA and RNA/cDNA of fecal samples from three groups of individuals by FLX technology: (i) healthy controls (no antibiotic therapy); (ii) individuals receiving antibiotic therapy (Ampicillin/Sulbactam, cephalosporins, and fluoroquinolones with subsequent development of C. difficile infection or (iii) individuals receiving antibiotic therapy without C. difficile infection. We compared the effects of the three different antibiotic classes on the intestinal microbiome and the effects of alterations of the gut microbiome on C. difficile infection at the DNA (total microbiota) and rRNA (potentially active) levels. A comparison of antibiotic classes showed significant differences at DNA level, but not at RNA level. Among individuals that developed or did not develop a C. difficile infection under antibiotics we found no significant differences. We identified single species that were up- or down regulated in individuals receiving antibiotics who developed the infection compared to non-infected individuals. We found no significant differences in the global composition of the transcriptionally active gut microbiome associated with C. difficile infections. We suggest that up- and down regulation of specific bacterial species may be involved in colonization resistance against C. difficile providing a potential therapeutic approach through specific manipulation of the intestinal microbiome. PMID:24586762

  13. Enhancing effect of serum ultrafiltrate on the activity of cephalosporins against gram-negative bacilli.

    PubMed Central

    Leggett, J E; Craig, W A

    1989-01-01

    A few studies have suggested that the inhibitory effect of serum on activity of broad-spectrum cephalosporins is less than that predicted by the degree of protein binding. Microdilution MICs of ceftriaxone, cefoperazone, moxalactam, and ceftizoxime were therefore determined against ATCC and clinical strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus in Mueller-Hinton broth containing either human albumin (as 0, 2.5, or 5% solution) or heat-inactivated human serum (as 0, 25, 50, or 95% solution). Arithmetic linear dilutions were used to improve accuracy. For standard bacterial strains, MICs in the presence of 5% albumin were higher than in broth alone by multiples of 10.9 to 21 for ceftriaxone, 5.5 to 16.4 for cefoperazone, 1.9 to 3.7 for moxalactam, and 1.1 to 1.4 for ceftizoxime, as expected by their protein binding. MICs in the presence of 95% serum were similar to those in 5% albumin for all four drugs against S. aureus and P. aeruginosa but were 2.2- to 4.8-fold lower (P less than 0.001) against E. coli and K. pneumoniae. Similar findings were observed at lower protein concentrations and with clinical isolates, except that for some strains of P. aeruginosa MICs were lower in serum than in albumin. Individual sera from five subjects gave comparable results. The addition of serum ultrafiltrate to albumin-containing solutions reduced MICs of ceftriaxone and cefoperazone 1.6- to 7.4-fold against E. coli and K. pneumoniae (P less than 0.01) but did not alter the MICs for S. aureus. Serum may contain an ultrafiltrable component(s) that enhances the activity of third-generation cephalosporins against many gram-negative bacilli. PMID:2496656

  14. Asexual Cephalosporin C Producer Acremonium chrysogenum Carries a Functional Mating Type Locus▿

    PubMed Central

    Pöggeler, Stefanie; Hoff, Birgit; Kück, Ulrich

    2008-01-01

    Acremonium chrysogenum, the fungal producer of the pharmaceutically relevant β-lactam antibiotic cephalosporin C, is classified as asexual because no direct observation of mating or meiosis has yet been reported. To assess the potential of A. chrysogenum for sexual reproduction, we screened an expressed sequence tag library from A. chrysogenum for the expression of mating type (MAT) genes, which are the key regulators of sexual reproduction. We identified two putative mating type genes that are homologues of the α-box domain gene, MAT1-1-1 and MAT1-1-2, encoding an HPG domain protein defined by the presence of the three invariant amino acids histidine, proline, and glycine. In addition, cDNAs encoding a putative pheromone receptor and pheromone-processing enzymes, as well as components of a pheromone response pathway, were found. Moreover, the entire A. chrysogenum MAT1-1 (AcMAT1-1) gene and regions flanking the MAT region were obtained from a genomic cosmid library, and sequence analysis revealed that in addition to AcMAT1-1-1 and AcMAT1-1-2, the AcMAT1-1 locus comprises a third mating type gene, AcMAT1-1-3, encoding a high-mobility-group domain protein. The α-box domain sequence of AcMAT1-1-1 was used to determine the phylogenetic relationships of A. chrysogenum to other ascomycetes. To determine the functionality of the AcMAT1-1 locus, the entire MAT locus was transferred into a MAT deletion strain of the heterothallic ascomycete Podospora anserina (the PaΔMAT strain). After fertilization with a P. anserina MAT1-2 (MAT+) strain, the corresponding transformants developed fruiting bodies with mature ascospores. Thus, the results of our functional analysis of the AcMAT1-1 locus provide strong evidence to hypothesize a sexual cycle in A. chrysogenum. PMID:18689517

  15. Cephalosporin therapy in intraabdominal infections. A multicenter randomized, comparative study of cefotetan, moxalactam, and cefoxitin.

    PubMed

    Wilson, S E; Boswick, J A; Duma, R J; Echols, R M; Jemsek, J G; Lerner, R; Lewis, R T; Najem, A Z; Press, R A; Rittenbury, M S

    1988-05-31

    Three broad-spectrum cephalosporins (cefotetan, moxalactam, and cefoxitin) proved effective in this randomized, prospective trial for treatment of 303 surgical patients with moderately severe regional peritonitis. PMID:3287971

  16. SK&F 75073, New Parenteral Broad-Spectrum Cephalosporin with High and Prolonged Serum Levels

    PubMed Central

    Actor, Paul; Uri, Joseph V.; Zajac, Ihor; Guarini, Joseph R.; Phillips, Lillian; Pitkin, Donald H.; Berges, David A.; Dunn, George L.; Hoover, John R. E.; Weisbach, Jerry A.

    1978-01-01

    SK&F 75073, a new parenteral cephalosporin, was found to have broad in vitro and in vivo antibacterial activity including isolates usually resistant to cephalothin and cefazolin. This activity included indole-positive Proteus and Enterobacter species and some Serratia isolates. Proteus mirabilis strains were particularly susceptible, as were Haemophilus influenzae and Neisseria species. The activity of SK&F 75073 against gram-positive bacteria was poorer than that of the control cephalosporins. This cephalosporin is highly bound to serum proteins, and a loss in in vitro activity was observed in the presence of serum. Parenteral administration of SK&F 75073 to experimental animals (mice, dogs, squirrel monkeys) resulted in high and prolonged serum levels when compared with cefazolin and other injectable cephalosporins. This favorable serum profile was reflected in the excellent protection observed in mice infected with pathogenic bacteria. PMID:96734

  17. Antibiotic sensitivity pattern; experience at University Hospital, Riyadh, Saudi Arabia.

    PubMed

    Chowdhury, M N

    1991-01-01

    Results of sensitivity testing were discussed based on examination of 5192 isolates of the various bacteria isolated from clinical specimens from King Khalid University Hospital in Riyadh, Saudi Arabia. Streptococcus pyogenes and Streptococcus pneumoniae were sensitive to penicillin and erythromycin. The sensitivity pattern of Staphylococcus aureus was also predictable as they were fairly sensitive to both methicillin (98%) and erythromycin (96%). Neisseria gonorrhoeae (27%) showed a high level of resistance to penicillin. The resistance of Haemophilus influenzae to ampicillin and chloramphenicol was low. Brucella species was sensitive to tetracycline and rifampicin; resistance to streptomycin and cotrimoxazole was minimal being 1% and 6% respectively. The resistance of E. coli, Klebsiella species and Proteus species to second and third generation cephalosporins and amikacin was fairly low ranging from 1.3% to 3%. The gentamicin resistance for these organisms was also within the acceptable range (3%-10%). Gentamicin and amikacin resistance for Pseudomonas aeruginosa was low (2-8%). Salmonella typhi was sensitive to ampicillin, cotrimoxazole, and chloramphenicol. Salmonella enteritidis, Shigella species, and enteropathogenic E. coli were highly resistant to various antibiotics. Campylobacter jejuni was sensitive to gentamicin but 6% of isolates were resistant to erythromycin. Ninety six percent of Gram-negative rods except P. aeruginosa isolated from urine of patients having urinary tract infections were sensitive to amoxycillin-clavulanic acid. In addition, P. aeruginosa showed fairly low resistance to norfloxacin which is given orally to treat cystitis caused by this organism. PMID:1960392

  18. Preparation and Properties of a Cephalosporin Acetylesterase Adsorbed onto Bentonite

    PubMed Central

    Abbott, Bernard J.; Fukuda, D. S.

    1975-01-01

    A cephalosporin acetylesterase produced by Bacillus subtilis was immobilized by adsorption onto bentonite. The immobilized enzyme (EI) and the soluble enzyme (ES) exhibited Michaelis-Menton kinetics with 7-aminocephalosporanic acid (7-ACA): Km = 2.8 10?3 M and Km = 3.2 10?3 M, respectively. Similar kinetics were observed with 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin), but the Km value measured with EI (3.7 10?3 M) was less than one-half that measured with this substrate and ES. The reduction in Km value was correlated with the ability of bentonite to adsorb cephalothin. The reaction products, acetate and deacetyl-7-ACA, were weak competitive inhibitors of ES and EI. The Ki values for EI were 5.0 10?2 M for acetate and 3.6 10?2 M for deacetyl-7-ACA. Similar values were measured with ES and these substrates. EI retained about 80% of its initial activity after 3 weeks of storage in solution at 25 C. However, the enzyme dissociated from the bentonite particles during the deacetylation reaction. This dissociation was minimized by cross-linking EI with glutaraldehyde or bis-dimethyladipimidate, or by adding Al(OH)3 to the suspension. With the latter addition, EI was stabilized so that it could be reused nine times before one-half of the initial activity was lost. PMID:241288

  19. A Comprehensive Assessment Across the Healthcare Continuum: Risk of Hospital-Associated Clostridium difficile Infection Due to Outpatient and Inpatient Antibiotic Exposure.

    PubMed

    Tartof, Sara Y; Rieg, Gunter K; Wei, Rong; Tseng, Hung Fu; Jacobsen, Steven J; Yu, Kalvin C

    2015-12-01

    BACKGROUND Limitations in sample size, overly inclusive antibiotic classes, lack of adjustment of key risk variables, and inadequate assessment of cases contribute to widely ranging estimates of risk factors for Clostridium difficile infection (CDI). OBJECTIVE To incorporate all key CDI risk factors in addition to 27 antibiotic classes into a single comprehensive model. DESIGN Retrospective cohort study. SETTING Kaiser Permanente Southern California. PATIENTS Members of Kaiser Permanente Southern California at least 18 years old admitted to any of its 14 hospitals from January 1, 2011, through December 31, 2012. METHODS Hospital-acquired CDI cases were identified by polymerase chain reaction assay. Exposure to major outpatient antibiotics (10 classes) and those administered during inpatient stays (27 classes) was assessed. Age, sex, self-identified race/ethnicity, Charlson Comorbidity Score, previous hospitalization, transfer from a skilled nursing facility, number of different antibiotic classes, statin use, and proton pump inhibitor use were also assessed. Poisson regression estimated adjusted risk of CDI. RESULTS A total of 401,234 patients with 2,638 cases of incident CDI (0.7%) were detected. The final model demonstrated highest CDI risk associated with increasing age, exposure to multiple antibiotic classes, and skilled nursing facility transfer. Factors conferring the most reduced CDI risk were inpatient exposure to tetracyclines and first-generation cephalosporins, and outpatient macrolides. CONCLUSIONS Although type and aggregate antibiotic exposure are important, the factors that increase the likelihood of environmental spore acquisition should not be underestimated. Operationally, our findings have implications for antibiotic stewardship efforts and can inform empirical and culture-driven treatment approaches. Infect. Control Hosp. Epidemiol. 2015;36(12):1409-1416. PMID:26387888

  20. Molecular Analysis of and Identification of Antibiotic Resistance Genes in Clinical Isolates of Salmonella typhi from India

    PubMed Central

    Shanahan, Philippa M. A.; Jesudason, Mary V.; Thomson, Christopher J.; Amyes, Sebastian G. B.

    1998-01-01

    A representative sample of 21 Salmonella typhi strains isolated from cultures of blood from patients at the Christian Medical College and Hospital, Vellore, India, were tested for their susceptibilities to various antimicrobial agents. Eleven of the S. typhi strains possessed resistance to chloramphenicol (256 mg/liter), trimethoprim (64 mg/liter), and amoxicillin (>128 mg/liter), while four of the isolates were resistant to each of these agents except for amoxicillin. Six of the isolates were completely sensitive to all of the antimicrobial agents tested. All the S. typhi isolates were susceptible to cephalosporin agents, gentamicin, amoxicillin plus clavulanic acid, and imipenem. The antibiotic resistance determinants in each S. typhi isolate were encoded by one of four plasmid types. Plasmid-mediated antibiotic resistance genes were identified with specific probes in hybridization experiments; the genes responsible for chloramphenicol, trimethoprim, and ampicillin resistance were chloramphenicol acetyltransferase type I, dihydrofolate reductase type VII, and TEM-1 β-lactamase, respectively. Pulsed-field gel electrophoresis analysis of XbaI-generated genomic restriction fragments identified a single distinct profile (18 DNA fragments) for all of the resistant isolates. In comparison, six profiles, different from each other and from the resistance profile, were recognized among the sensitive isolates. It appears that a single strain containing a plasmid conferring multidrug-resistance has emerged within the S. typhi bacterial population in Vellore and has been able to adapt to and survive the challenge of antibiotics as they are introduced into clinical medicine. PMID:9620383

  1. Soil-borne reservoirs of antibiotic-resistant bacteria are established following therapeutic treatment of dairy calves.

    PubMed

    Liu, Jinxin; Zhao, Zhe; Orfe, Lisa; Subbiah, Murugan; Call, Douglas R

    2016-02-01

    We determined if antibiotics residues that are excreted from treated animals can contribute to persistence of resistant bacteria in agricultural environments. Administration of ceftiofur, a third-generation cephalosporin, resulted in a???3 log increase in ceftiofur-resistant Escherichia coli found in the faeces and pen soils by day 10 (P?=?0.005). This resistant population quickly subsided in faeces, but was sustained in the pen soil (??4.5 log bacteria?g(-1) ) throughout the trial (1 month). Florfenicol treatment resulted in a similar pattern although the loss of florfenicol-resistant E.?coli was slower for faeces and remained stable at ??6 log bacteria?g(-1) in the soil. Calves were treated in pens where eGFP-labelled E.?coli were present in the bedding (??2 log?g(-1) ) resulting in amplification of the eGFP E.?coli population ??2.1 log more than eGFP E.?coli populations in pens with untreated calves (day 4; P??10-fold greater contribution to the bedding reservoir compared with shedding of resistant bacteria in faeces. Treatment with therapeutic doses of ceftiofur or florfenicol resulted in 2-3 log?g(-1) more bacteria than the estimated ID50 (2.83 CFU?g(-1) ), consistent with a soil-borne reservoir emerging after antibiotic treatment that can contribute to the long-term persistence of antibiotic resistance in animal agriculture. PMID:26486254

  2. Antibiotic prescribing in women during and after delivery in a non-teaching, tertiary care hospital in Ujjain, India: a prospective cross-sectional study

    PubMed Central

    2013-01-01

    Objectives Antibacterial drugs (hereafter referred to as antibiotics) are crucial to treat infections during delivery and postpartum period to reduce maternal mortality. Institutional deliveries have the potential to save lives of many women but extensive use of antibiotics, add to the development and spread of antibiotic resistance. The aim of this study was to present antibiotic prescribing among inpatients during and after delivery in a non-teaching, tertiary care hospital in the city of Ujjain, Madhya Pradesh, India. Methods A prospective cross-sectional study was conducted including women having had either a vaginal delivery or a cesarean section in the hospital. Trained nursing staff collected the data on daily bases, using a specific form attached to each patient file. Statistical analysis, including bivariate and multivariable logistic regression was conducted. Results Of the total 1077 women, 566 (53%) had a vaginal delivery and 511 (47%) had a cesarean section. Eighty-seven percent of the women that had a vaginal delivery and 98% of the women having a cesarean section were prescribed antibiotics. The mean number of days on antibiotics in hospital for the women with a vaginal delivery was 3.1 (1.7) and for the women with cesarean section was 6.0 (2.5). Twenty-eight percent of both the women with vaginal deliveries and the women with cesarean sections were prescribed antibiotics at discharge. The most commonly prescribed antibiotic group in the hospital for both the women that had a vaginal delivery and the women that had a cesarean section were third-generation cephalosporins (J01DD). The total number of defined daily doses (DDD) per100 bed days for women that had a vaginal delivery was 101, and 127 for women that had a cesarean section. Conclusions The high percentage of women having had a vaginal delivery that received antibiotics and the deviation from recommendation for cesarean section in the hospital is a cause of concern. Improved maternal health and rational use of antibiotics are intertwined. Specific policy and guidelines on how to prescribe antibiotics during delivery at health care facilities are needed. Additionally, monitoring system of antibiotic prescribing and resistance needs to be developed and implemented. PMID:25848538

  3. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

    PubMed Central

    Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang

    2014-01-01

    In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge. PMID:24905407

  4. The effect of antibiotic exposure on eicosanoid generation from arachidonic acid and gene expression in a primitive chordate, Branchiostoma belcheri

    PubMed Central

    Yuan, Dongjuan; Pan, Minming; Zou, Qiuqiong; Chen, Chengyong; Chen, Shangwu; Xu, Anlong

    2015-01-01

    Chloramphenicol (Chl) is an effective antimicrobial agent widely used in veterinary medicine and commonly used in fish. Its use is restricted in the clinic because of adverse effects on the immune system and oxidative stress in mammals. However, the effects of Chl treatment on invertebrates remain unclear. Amphioxus, a basal chordate, is an ideal model to study the origin and evolution of the vertebrate immune system as it has a primary vertebrate-like arachidonic acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic approaches to investigate the immune system and observe the oxygenated metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial cells were lost when treated with both Chl and ampicillin (Amp). The immune related pathways were dysregulated in both of the antibiotic treatment groups. The Chl alone treatment resulted in immunosuppression with down-regulation of the innate immune genes. In contrast, the Chl+Amp treatment resulted in immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl induced a 3-fold reduction in the level of the eicosanoids, while the Chl+Amp treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus, Amp might relieve the effects of the Chl-induced immune suppression and increase the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA might be crucial to evaluate the effects of Chl treatment in animals. PMID:26288743

  5. Antibiotic prophylaxis during clean neurosurgery: a large, multicenter study using cefuroxime.

    PubMed

    Holloway, K L; Smith, K W; Wilberger, J E; Jemsek, J G; Giguere, G C; Collins, J J

    1996-01-01

    Cefuroxime is a second-generation cephalosporin with in vitro activity against the organisms that are commonly associated with neurosurgical wound infections. Other properties of cefuroxime are an elimination half-life of 1.3 hours, which yields prolonged serum concentrations, and its ability to penetrate the blood-brain barrier in proportion to the degree of inflammation. A prospective, multicenter, open-label study was conducted to evaluate the efficacy and safety of cefuroxime for antibiotic prophylaxis in patients undergoing clean neurosurgery. Cefuroxime 1.5 g was given intravenously 25 to 60 minutes before surgery; for procedures lasting more than 3 hours, cefuroxime 750 mg was given intravenously 8 hours after the initial dose. Patients were examined before surgery, daily during hospitalization, and at 8 weeks after surgery. A total of 956 adults were enrolled in the study. The most common procedures in study patients were laminectomy (41.8% of patients) or craniotomy (24.3%), and the mean duration of surgery was 3.2 hours. Infection occurred in 2 (0.3%) of 592 assessable patients by the time of discharge and in 1 additional patient by the 8-week follow-up evaluation for a total of 3 (0.5%) of 560 assessable patients. Drug-related adverse events occurred in 5 (0.5%) of 956 patients. These results indicate that antibiotic prophylaxis with cefuroxime is associated with a low incidence of postoperative wound infection and is well tolerated in patients undergoing clean neurosurgery. PMID:8851455

  6. Assessment of copper and zinc salts as selectors of antibiotic resistance in Gram-negative bacteria.

    PubMed

    Becerra-Castro, Cristina; Machado, Rita A; Vaz-Moreira, Ivone; Manaia, Clia M

    2015-10-15

    Some metals are nowadays considered environmental pollutants. Although some, like Cu and Zn, are essential for microorganisms, at high concentrations they can be toxic or exert selective pressures on bacteria. This study aimed to assess the potential of Cu or Zn as selectors of specific bacterial populations thriving in wastewater. Populations of Escherichia coli recovered on metal-free and metal-supplemented culture medium were compared based on antibiotic resistance phenotype and other traits. In addition, the bacterial groups enriched after successive transfers in metal-supplemented culture medium were identified. At a concentration of 1mM, Zn produced a stronger inhibitory effect than Cu on the culturability of Enterobacteriaceae. It was suggested that Zn selected populations with increased resistance prevalence to sulfamethoxazole or ciprofloxacin. In non-selective culture media, Zn or Cu selected for mono-species populations of ubiquitous Betaproteobacteria and Flavobacteriia, such as Ralstonia pickettii or Elizabethkingia anophelis, yielding multidrug resistance profiles including resistance against carbapenems and third generation cephalosporins, confirming the potential of Cu or Zn as selectors of antibiotic resistant bacteria. PMID:26057541

  7. [Antibiotic prophylaxis in colorectal surgery].

    PubMed

    Dellamonica, P; Bernard, E

    1994-01-01

    In elective colorectal surgery, the benefit of preoperative antibiotic prophylaxis is well established, with a reduction in wound infection rate to less than 10%. The antimicrobial agent used has to be active against aerobic and anaerobic pathogens such as Escheria coli and Bacteriodes fragilis. The efficacy of three schemes of administration: oral and/or parenteral prophylaxis associated with a mechanical preparation, has been demonstrated. Oral antibiotic administration is current practice in USA; the most widely used oral regimen is the combination of erythromycin and neomycin given the day before surgery. Parenteral prophylaxis with a cephalosporin active against Bacteriodes fragilis such as cefoxitin and cefotetan, is preferred in Europe. The issue of whether a systemic prophylaxis should be added to the oral regimen or not has not yet been resolved. However it seems that the association should be proposed in various situations: patients with a high risk factors score (rectal resection and operations lasting more than three hours), patients with incomplete mechanical preparation, delay of the onset of surgery after the last oral dose. PMID:7778802

  8. Thin Layer Chromatographic Analysis of Beta-Lactam Antibiotics

    PubMed Central

    Hancu, Gabriel; Simon, Brigitta; Kelemen, Hajnal; Rusu, Aura; Mircia, Eleonora; Gyresi, rpd

    2013-01-01

    Purpose: The paper describes some thin layer chromatographic procedures that allow simple and rapid separation and identification of penicillins and cephalosporins from complex mixtures. Methods: Using silicagel GF254 as stationary phase and selecting different mobile phases we succeeded in the separation of the studied beta-lactamins. Our aim was not only to develop a simple, rapid and efficient method for their separation but also the optimization of the analytical conditions. Results: No system will separate all the beta-lactams, but they could be identified when supplementary information is used from color reactions and/or by using additional chromatographic systems. Conclusion: The right combination of solvent system and detection method allows the identification of the studied penicillins and cephalosporins and can be successfully used in the preliminary analysis beta-lactam antibiotics. PMID:24312862

  9. Antibiotics Quiz

    MedlinePLUS

    ... on the Farm Get Smart About Antibiotics Week File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  10. Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital

    PubMed Central

    Niwa, T; Shinoda, Y; Suzuki, A; Ohmori, T; Yasuda, M; Ohta, H; Fukao, A; Kitaichi, K; Matsuura, K; Sugiyama, T; Murakami, N; Itoh, Y

    2012-01-01

    Background Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan. Methods The infection control team was involved in the review of individual use of antibiotics in all inpatients (6348 and 6507 patients/year during the first and second annual interventions, respectively) receiving intravenous antibiotics, according to the published guidelines, consultation with physicians before prescription of antimicrobial agents and organisation of education programme on infection control for all medical staff. The outcomes of extensive implementation of antimicrobial stewardship were evaluated from the standpoint of antimicrobial use density, treatment duration, duration of hospital stay, occurrence of antimicrobial-resistant bacteria and medical expenses. Results Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p < 0.001). Significant reduction in the antimicrobial consumption was observed in the second-generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p < 0.001), leading to a reduction in the cost of antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship. Conclusion Extensive implementation of antimicrobial stewardship led to a decrease in the inappropriate use of antibiotics, saving in medical expenses, reduction in the development of antimicrobial resistance and shortening of hospital stay. PMID:22846073

  11. Retrospective analysis of antibiotic resistance pattern to urinary pathogens in a Tertiary Care Hospital in South India

    PubMed Central

    Somashekara, Saligrama Chikkannasetty; Deepalaxmi, Salmani; Jagannath, Narumalla; Ramesh, Bannaravuri; Laveesh, Madathil Ravindran; Govindadas, Damodaram

    2014-01-01

    Context: The distribution of uropathogens and their susceptibility pattern to antibiotics vary regionally and even in the same region, they change over time. Therefore, the knowledge on the frequency of the causative microorganisms and their susceptibility to various antibiotics are necessary for a better therapeutic outcome. Aim: The aim was to study the frequency and distribution of uropathogens and their resistance pattern to antibiotics in a tertiary care hospital. Settings and Design: Retrospective study for a period of 1 year from January 2011 to December 2011 in a tertiary care hospital. Materials and Methods: The culture and sensitivity data of the uropathogens from suspected cases of UTI were collected from the records of Microbiology Department for study period. Midstream urine samples were processed for microscopy and culture, and the organisms were identified by standard methods. Antibiotic susceptibility was carried out by Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. Descriptive statistics were used to analyze the data. Results: Of 896 urine samples, 348 (38.84%) samples were positive for urine culture. Escherichia coli (52.59%) was the most common organism followed by Klebsiella. E. coli was least resistant to imipenem (8%) and amikacin (16%) and was highly resistant to co-trimoxazole (69%) and ampicillin (86%). Klebsiella species were least resistant to amikacin (26%) and were highly resistant to ampicillin (92%). The overall resistance pattern of antibiotics to uropathogens was the highest to nalidixic acid (79%) followed by co-trimoxazole (75%) and ampicillin (72%). Good susceptibility was seen with imipenem and cephalosporins. Conclusion: E. coli is still the most common uropathogen. Nalidixic acid, ampicillin, co-trimoxazole, and first-generation fluoroquinolones have limited value for the treatment of UTI. Sensitivity to imipenem and amikacin are still retained and may be prescribed for complicated UTI. Routine monitoring of drug resistance pattern will help to identify the resistance trends regionally. This will help in the empirical treatment of UTIs to the clinicians. PMID:25316990

  12. TCA cycle-mediated generation of ROS is a key mediator for HeR-MRSA survival under β-lactam antibiotic exposure.

    PubMed

    Rosato, Roberto R; Fernandez, Regina; Paz, Liliana I; Singh, Christopher R; Rosato, Adriana E

    2014-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug resistant pathogen responsible for several difficult-to-treat infections in humans. Clinical Hetero-resistant (HeR) MRSA strains, mostly associated with persistent infections, are composed of mixed cell populations that contain organisms with low levels of resistance (hetero-resistant HeR) and those that display high levels of drug resistance (homo-resistant HoR). However, the full understanding of β-lactam-mediated HeR/HoR selection remains to be completed. In previous studies we demonstrated that acquisition of the HoR phenotype during exposure to β-lactam antibiotics depended on two key elements: (1) activation of the SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, resulting in increased mutation rates, and (2) adaptive metabolic changes redirecting HeR-MRSA metabolism to the tricarboxylic acid (TCA) cycle in order to increase the energy supply for cell-wall synthesis. In the present work, we identified that both main mechanistic components are associated through TCA cycle-mediated reactive oxygen species (ROS) production, which temporally affects DNA integrity and triggers activation of the SOS response resulting in enhanced mutagenesis. The present work brings new insights into a role of ROS generation on the development of resistance to β-lactam antibiotics in a model of natural occurrence, emphasizing the cytoprotective role in HeR-MRSA survival mechanism. PMID:24932751

  13. Anaerobic stabilization and conversion of transformed intermediates of antibiotic pharmaceutical effluent in a fluidized bed reactor.

    PubMed

    Tamijevendane, S; Saravanane, R; Rajesh, R; Sivacoumar, R

    2011-07-01

    The formulation and implementation of regulatory standards for the ultimate disposal and reuse of transformed products of antibiotic drugs and solvents have been a pending issue in the waste management of pharmaceutical industries especially in the developing countries like India. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible implementation of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. The objective of the study was to determine the effect of bioaugmentation on the convertibility of anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge into residuals and biocompost. Cephalosporin is a common name refers to cephradine (C16H19N3O4S) and cephalexin (C16H17N3O4S.H2O). Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented in India does not envisage such disposal alternatives and hence this would invite suggestions and recommendations of the expertise for the possible implementation on the pending issue in the antibiotic based pharmaceutical industries. The presence of cephalosporin increases total strength (Chemical Oxygen Demand) of the effluent and indirectly increases the cost of the treatment. Hence the biotransformation of cephalosporin either alone or in combination with other energetic compounds, offers the potential for an economical and environment friendly disposal alternative for the anaerobically transformed intermediates of antibiotic pharmaceutical waste sludge. PMID:23029922

  14. Genomic Epidemiology of Klebsiella pneumoniae in Italy and Novel Insights into the Origin and Global Evolution of Its Resistance to Carbapenem Antibiotics

    PubMed Central

    Gaiarsa, Stefano; Comandatore, Francesco; Gaibani, Paolo; Corbella, Marta; Dalla Valle, Claudia; Epis, Sara; Scaltriti, Erika; Carretto, Edoardo; Farina, Claudio; Labonia, Maria; Landini, Maria Paola; Sambri, Vittorio; Bandi, Claudio; Marone, Piero

    2014-01-01

    Klebsiella pneumoniae is at the forefront of antimicrobial resistance for Gram-negative pathogenic bacteria, as strains resistant to third-generation cephalosporins and carbapenems are widely reported. The worldwide diffusion of these strains is of great concern due to the high morbidity and mortality often associated with K. pneumoniae infections in nosocomial environments. We sequenced the genomes of 89 K. pneumoniae strains isolated in six Italian hospitals. Strains were selected based on antibiotypes, regardless of multilocus sequence type, to obtain a picture of the epidemiology of K. pneumoniae in Italy. Thirty-one strains were carbapenem-resistant K. pneumoniae carbapenemase producers, 29 were resistant to third-generation cephalosporins, and 29 were susceptible to the aforementioned antibiotics. The genomes were compared to all of the sequences available in the databases, obtaining a data set of 319 genomes spanning the known diversity of K. pneumoniae worldwide. Bioinformatic analyses of this global data set allowed us to construct a whole-species phylogeny, to detect patterns of antibiotic resistance distribution, and to date the differentiation between specific clades of interest. Finally, we detected an ?1.3-Mb recombination that characterizes all of the isolates of clonal complex 258, the most widespread carbapenem-resistant group of K. pneumoniae. The evolution of this complex was modeled, dating the newly detected and the previously reported recombination events. The present study contributes to the understanding of K. pneumoniae evolution, providing novel insights into its global genomic characteristics and drawing a dated epidemiological scenario for this pathogen in Italy. PMID:25367909

  15. Porin Involvement in Cephalosporin and Carbapenem Resistance of Burkholderia pseudomallei

    PubMed Central

    Aunkham, Anuwat; Schulte, Albert; Winterhalter, Mathias; Suginta, Wipa

    2014-01-01

    Background Burkholderia pseudomallei (Bps) is a Gram-negative bacterium that causes frequently lethal melioidosis, with a particularly high prevalence in the north and northeast of Thailand. Bps is highly resistant to many antimicrobial agents and this resistance may result from the low drug permeability of outer membrane proteins, known as porins. Principal Findings Microbiological assays showed that the clinical Bps strain was resistant to most antimicrobial agents and sensitive only to ceftazidime and meropenem. An E. coli strain defective in most porins, but expressing BpsOmp38, exhibited considerably lower antimicrobial susceptibility than the control strain. In addition, mutation of Tyr119, the most prominent pore-lining residue in BpsOmp38, markedly altered membrane permeability, substitution with Ala (mutant BpsOmp38Y119A) enhanced uptake of the antimicrobial agents, while substitution with Phe (mutant BpsOmp38Y119F) inhibited uptake. Channel recordings of BpsOmp38 reconstituted in a planar black lipid membrane (BLM) suggested that the higher permeability of BpsOmp38Y119A was caused by widening of the pore interior through removal of the bulky side chain. In contrast, the lower permeability of BpsOmp38Y119F was caused by introduction of the hydrophobic side chain (Phe), increasing the greasiness of the pore lumen. Significantly, liposome swelling assays showed no permeation through the BpsOmp38 channel by antimicrobial agents to which Bps is resistant (cefoxitin, cefepime, and doripenem). In contrast, high permeability to ceftazidime and meropenem was observed, these being agents to which Bps is sensitive. Conclusion/Significance Our results, from both in vivo and in vitro studies, demonstrate that membrane permeability associated with BpsOmp38 expression correlates well with the antimicrobial susceptibility of the virulent bacterium B. pseudomallei, especially to carbapenems and cephalosporins. In addition, substitution of the residue Tyr119 affects the permeability of the BpsOmp38 channel to neutral sugars and antimicrobial agents. PMID:24788109

  16. The Beta Lactam Antibiotics as an Empirical Therapy in a Developing Country: An Update on Their Current Status and Recommendations to Counter the Resistance against Them

    PubMed Central

    Thakuria, Bhaskar; Lahon, Kingshuk

    2013-01-01

    In a developing country like India, where the patients have to bear the cost of their healthcare, the microbiological culture and the sensitivity testing of each and every infection is not feasible. Moreover, there are lacunae in the data storage, management and the sharing of knowledge with respect to the microorganisms which are prevalent in the local geographical area and with respect to the antibiotics which are effective against them. Thus, an empirical therapy for treating infections is imperative in such a setting. The beta lactam antibiotics have been widely used for the empirical treatment of infections since the the discovery of penicillin. Many generations of beta lactams have been launched with, the claims of a higher sensitivity and less resistance, but their sensitivity has drastically decreased over time. Thus, the preference for beta lactams, especially the cephalosporins, as an empirical therapy, among the prescribers was justified initially, but the current sensitivity patterns do not support their empirical use in hospital and community acquired infections. There is a need for increasing the awareness and the attitudinal change among the prescribers, screening of the antibiotic prescriptions, the strict implementation of antibiotic policies in hospital settings, restricting the hospital supplies and avoiding the prescriptions of beta lactams, a regular census of the local sensitivity patterns to formulate and update the antibiotic policies, upgradation of the laboratory facilities for a better and faster detection of the isolates, proper collection, analyses and sharing of the data and the encouragement of the research and development of newer antibiotics with novel mechanisms of action. PMID:23905143

  17. Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs.

    PubMed

    Hu, Youjia; Peng, Jian; Tai, Ningwen; Hu, Changyun; Zhang, Xiaojun; Wong, F Susan; Wen, Li

    2015-11-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that involves the slow, progressive destruction of islet β cells and loss of insulin production, as a result of interaction with environmental factors, in genetically susceptible individuals. The gut microbiome is established very early in life. Commensal microbiota establish mutualism with the host and form an important part of the environment to which individuals are exposed in the gut, providing nutrients and shaping immune responses. In this study, we studied the impact of targeting most Gram-negative bacteria in the gut of NOD mice at different time points in their life, using a combination of three antibiotics--neomycin, polymyxin B, and streptomycin--on diabetes development. We found that the prenatal period is a critical time for shaping the immune tolerance in the progeny, influencing development of autoimmune diabetes. Prenatal neomycin, polymyxin B, and streptomycin treatment protected NOD mice from diabetes development through alterations in the gut microbiota, as well as induction of tolerogenic APCs, which led to reduced activation of diabetogenic CD8 T cells. Most importantly, we found that the protective effect was age dependent, and the most profound protection was found when the mice were treated before birth. This indicates the importance of the prenatal environment and early exposure to commensal bacteria in shaping the host immune system and health. PMID:26401004

  18. Identification of a ferritin-like protein of Listeria monocytogenes as a mediator of β-lactam tolerance and innate resistance to cephalosporins

    PubMed Central

    2012-01-01

    Background The food-borne pathogen Listeria monocytogenes is the causative agent of listeriosis. The β-lactam antibiotics penicillin G and ampicillin are the current drugs of choice for the treatment of listerial infections. While isolates of L. monocytogenes are susceptible to these antibiotics, their action is only bacteriostatic and consequently, this bacterium is regarded as tolerant to β-lactams. In addition, L. monocytogenes has a high level of innate resistance to the cephalosporin family of β-lactams frequently used to treat sepsis of unknown etiology. Given the high mortality rate of listeriosis despite rational antibiotic therapy, it is important to identify genes that play a role in the susceptibility and tolerance of L. monocytogenes to β-lactams. Results The hly-based promoter trap system was applied to identify penicillin G-inducible genes of L. monocytogenes. The results of reporter system studies, verified by transcriptional analysis, identified ten penicillin G-inducible genes. The contribution of three of these genes, encoding a ferritin-like protein (fri), a two-component phosphate-response regulator (phoP) and an AraC/XylS family transcriptional regulator (axyR), to the susceptibility and tolerance of L. monocytogenes to β-lactams was examined by analysis of nonpolar deletion mutants. The absence of PhoP or AxyR resulted in more rapid growth of the strains in the presence of sublethal concentration of β-lactams, but had no effect on the MIC values or the ability to survive a lethal dose of these antibiotics. However, the Δfri strain showed impaired growth in the presence of sublethal concentrations of penicillin G and ampicillin and a significantly reduced ability to survive lethal concentrations of these β-lactams. A lack of Fri also caused a 2-fold increase in the sensitivity of L. monocytogenes to cefalotin and cephradine. Conclusions The present study has identified Fri as an important mediator of β-lactam tolerance and innate resistance to cephalosporins in L. monocytogenes. PhoP and AxyR are probably involved in transmitting signals to adjust the rate of growth of L. monocytogenes under β-lactam pressure, but these regulators do not play a significant role in susceptibility and tolerance to this class of antibiotics. PMID:23176286

  19. Total Synthesis of the Antitumor Antibiotic ()-Streptonigrin: First- and Second-Generation Routes for de Novo Pyridine Formation Using Ring-Closing Metathesis

    PubMed Central

    2013-01-01

    The total synthesis of ()-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing ()-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric SuzukiMiyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time. PMID:24328139

  20. Effect of loading rate and HRT on the removal of cephalosporin and their intermediates during the operation of a membrane bioreactor treating pharmaceutical wastewater.

    PubMed

    Sundararaman, S; Saravanane, R

    2010-01-01

    The viability of treating high-concentration antibiotic wastewater by a membrane bioreactor (MBR) was studied using submerged flat sheet membrane. The major problems for these modules are concentration polarization and subsequent fouling. By using gas-liquid two-phase flow, these problems can be ameliorated. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible removal of anaerobically transformed intermediates of antibiotic pharmaceutical wastewater. The objective of the study was to determine the effect of organic loading rate and hydraulic retention time on the removal of cephalosporin derivative, viz., cephalexin (C(16)H(17)N(3)O(4)S.H(2)O) and the intermediates [7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and acyl group (Phenyl acetic acid)] in the MBR with enhanced biodegradation using bioaugmentation technique. Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-ADCA and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented at a global level, (meaning the intermediates which are transformed during its course of travel within the industry and in the treatments plants, i.e., in the present study it is, 7-ADCA and phenyl acetic acid are not allowed to discharge on water bodies), does not envisage such disposal alternatives and hence the present study was aimed at the complete removal of intermediates (7-ADCA) and phenyl acetic acid prior to discharge. PMID:20371950

  1. Reverse phase high speed liquid chromatography of antibiotics.

    PubMed

    White, E R; Carroll, M A; Zarembo, J E; Bender, A D

    1975-03-01

    Reverse phase high speed liquid chromatographic methods are presented for the separation and detection of cephalosporins, penicillins, tetracyclines and other miscellaneous antibiotics. The reverse phase approach is superior to ion-exchange liquid chromatography and spectrophotometric, chemical and microbiological procedures currently in use. In addition to being simple and easy to control, the technique is rapid, convenient and precise and provides the basis for the direct analysis of pure compounds, stability samples, complex mixtures and dosage forms of all types. Preparative chromatography has been used in our laboratory for the separation and isolation of up to 500 mg of antibiotics. Using this approach, we have separated and isolated small impurities as well as pure feference compounds. The methodology reported here can be extensively applied to the separation, quantitation and isolation of both naturally occurring and synthetically produced antibiotics in a variety of media including physiological fluids. PMID:1126874

  2. Improving known classes of antibiotics: an optimistic approach for the future.

    PubMed

    Bush, Karen

    2012-10-01

    New antibiotic agents are desperately needed to treat the multidrug-resistant pathogens that continue to emerge at alarming rates. Many of the agents that have entered full clinical development since 1995 have been members of previously accepted classes of antibiotics. Among these are a new aminoglycoside (plazomicin), anti-MRSA cephalosporins (ceftobiprole and ceftaroline), a monocyclic ?-lactam (BAL30072), the ?-lactamase inhibitor combination of tazobactam with the anti-pseudomonal cephalosporin ceftolozane, ?-lactam combinations with new non-?-lactam inhibitors (MK-7655 with imipenem, and avibactam with ceftazidime and ceftaroline), new macrolides (cethromycin and solithromycin), oxazolidinones (tedizolid phosphate and radezolid), and quinolones (delafloxacin, nemonoxacin and JNJ-Q2). Resistance and safety issues have been circumvented by some of these new agents that have well-established mechanisms of action and defined pathways leading toward regulatory approval. PMID:22748801

  3. Prophylactic antibiotic trends in transsphenoidal surgery for pituitary lesions.

    PubMed

    Little, Andrew S; White, William L

    2011-06-01

    Pituitary surgery involves operating in the nasal cavity, which is considered a clean-contaminated wound. In the absence of evidence-based guidelines for preventing surgical site infections in trans-sphenoidal surgery, a survey of current opinion on prophylactic antibiotics might help elucidate the current acceptable practices and identify opportunities for prospective clinical trials that could lead to the development of practice guidelines. An on-line, 10-question, multiple-choice survey was distributed by e-mail link to the membership of the International Society of Pituitary Surgeons. Sixty-nine members responded to the survey. Ninety-one percent indicated that there was no strong evidence supporting antibiotic use, but 81% used them to be safe. Ninety percent of respondents used intravenous prophylactic antibiotics, while only 16% used intranasal antibiotics. The most commonly used antibiotics were cephalosporins (72%) and penicillins (21%). Seventy-six percent used antibiotics for 24 h or less after surgery. The most commonly reported indications for prophylactic antibiotics were prevention of meningitis and sinusitis. The results of the survey describe current acceptable practices for chemoprophylaxis in patients undergoing transsphenoidal pituitary surgery. PMID:20809111

  4. Nosocomial infection and its molecular mechanisms of antibiotic resistance.

    PubMed

    Xia, Jufeng; Gao, Jianjun; Tang, Wei

    2016-03-10

    Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized. PMID:26877142

  5. Biochemical and Clinical Characteristics and Antibiotic Susceptibility of Atypical Enterobacter cloacae

    PubMed Central

    Washington, John A.; Yu, Pauline; Martin, William J.

    1969-01-01

    The characteristics of an atypical group of the family Enterobacteriaceae resembling Enterobacter cloacae were studied. The urinary tract was the most common source of these organisms, and most strains represented infections of secondary clinical significance. In contrast to typical Enterobacter strains, the atypical strains were highly susceptible to the cephalosporins; otherwise, there was a high degree of susceptibility to five other antibiotics and resistance to ampicillin except in very high concentration. PMID:4307882

  6. Increased expression levels of chromosomal AmpC β-lactamase in clinical Escherichia coli isolates and their effect on susceptibility to extended-spectrum cephalosporins.

    PubMed

    Paltansing, Sunita; Kraakman, Margriet; van Boxtel, Ria; Kors, Ivo; Wessels, Els; Goessens, Wil; Tommassen, Jan; Bernards, Alexandra

    2015-02-01

    Forty-nine clinical Escherichia coli isolates, both extended-spectrum β-lactamase (ESBL) negative and ESBL positive, were studied to investigate whether increased AmpC expression is a mechanism involved in cefoxitin resistance and if this influences the third-generation cephalosporin activity. Nine of 33 (27.2%) cefoxitin-resistant (minimum inhibitory concentration [MIC] >8 mg/L) isolates showed hyperproduction of chromosomal AmpC (c-AmpC) based on (1) at least two positive tests using AmpC inhibitors, (2) mutations in the promoter/attenuator regions, and (3) a 6.1- to 163-fold increase in c-ampC expression by quantitative reverse transcription-polymerase chain reaction. In ESBL-negative isolates, MICs of ceftazidime and cefotaxime were mostly above the wild-type (WT) level, but below the S/I breakpoint (EUCAST guideline), except for one isolate with MICs of 4 mg/L. No plasmid-mediated AmpCs were found. Periplasmic extracts of nine c-AmpC hyperproducers were preincubated with or without cefuroxime or ceftazidime and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cefuroxime and ceftazidime were stable to hydrolysis but acted as inhibitors of the enzyme. None of these isolates showed loss of porins. Thus, cefoxitin resistance has low specificity for detecting upregulated c-AmpC production. c-AmpC hyperproducing E. coli is mostly still susceptible to third-generation cephalosporins but less than WT E. coli. Surveillance of cefoxitin-resistant E. coli to monitor developments in the activity of third-generation cephalosporins against c-AmpC hyperproducers is warranted. PMID:25188329

  7. Antibiotic-Resistant Fecal Bacteria, Antibiotics, and Mercury in Surface Waters of Oakland County, Michigan, 2005-2006

    USGS Publications Warehouse

    Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

    2007-01-01

    Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony-forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance genes (class I integrons) were detected in several samples, indicating that the resistance carried by these organisms may be transferable to other bacteria, including disease-causing bacteria.

  8. [Multicenter study of the antibacterial activity of a new cephalosporin: CM 40874].

    PubMed

    Duval, J; Soussy, C J; Deforges, L; Brun, Y; Coulet, M; Forey, F; Thabaut, A; Meyran, M; Acar, J F; Kitzis, M D

    1984-05-01

    Minimal inhibitory concentrations (MIC) of CM were evaluated on 2 548 bacterial strains isolated in 8 hospitals. CM demonstrated high activity on Enterobacteriaceae, the MIC being less than or equal to 0.125 micrograms/ml for 71% of the 1 362 strains tested, less than or equal to 1 for 99.6%, and less than or equal to 4 for 99.9%. Mode MIC varies little among the different groups of Enterobacteriaceae (from 0.06 to 0.12 micrograms/ml), with the exception of Serratia sp. (mode MIC : 0.25) and Klebsiella oxytoca (mode MIC : 0.03). Most of Enterobacter, Serratia, and Citrobacter sp. strains not inhibited by cefotaxime are readily inhibited by CM at the same concentrations than susceptible strains. CM has less activity on P. aeruginosa (MIC 2-32 micrograms/ml) and Acinetobacter sp. (MIC 8-128). Staphylococci (MIC 32) and Enterococci are not susceptible. Variable activity is found against other Streptococci. CM inhibits Haemophilus sp. at MICs of 0.12 to 0.5 micrograms/ml and Gonococci at MICs of 0.03 to 0.5 (whether the strains produce beta-lactamase or not). Meningococci have a mode MIC of 0.03 micrograms/ml (range 0.008 to 0.25). Thus, CM 40874 is a new third generation cephalosporin with high activity on Enterobacteriaceae, including those strains not susceptible to cefotaxime and good activity on Haemophilus sp. and Neisseria sp. This additional activity is probably supported by enhanced resistance to enzymatic inactivation by beta-lactamases. PMID:6547524

  9. New antibiotics against gram-positives: present and future indications.

    PubMed

    Morata, Laura; Mensa, Josep; Soriano, Alex

    2015-10-01

    Gram-positive cocci are the most frequent aetiology of community and nosocomially bacterial acquired infections. The prevalence of multidrug-resistant gram-positive bacteria is increasing and is associated with high morbidity and mortality. New antibiotics will be available in the European market during the next months. This revision is focused on lipoglycopeptides, new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA) and the new oxazolidinone, tedizolid. The purpose of this review is to describe their in vitro activity, pharmacokinetic and pharmacodynamic characteristics, and experience from clinical trials. PMID:26232669

  10. Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada

    PubMed Central

    Sawatzky, P.; Liu, G.; Allen, V; Lefebvre, B.; Hoang, L.; Drews, S.; Horsman, G.; Wylie, J.; Haldane, D.; Garceau, R.; Ratnam, S.; Wong, T.; Archibald, C.; Mulvey, M.R.

    2016-01-01

    Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010–2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines. PMID:26689114

  11. Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada.

    PubMed

    Martin, I; Sawatzky, P; Liu, G; Allen, V; Lefebvre, B; Hoang, L; Drews, S; Horsman, G; Wylie, J; Haldane, D; Garceau, R; Ratnam, S; Wong, T; Archibald, C; Mulvey, M R

    2016-01-01

    Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010-2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines. PMID:26689114

  12. The incidence of antibiotic resistance in aerobic faecal flora in south India.

    PubMed

    Amyes, S G; Tait, S; Thomson, C J; Payne, D J; Nandivada, L S; Jesudason, M V; Mukundan, U D; Young, H K

    1992-04-01

    During a field study in South India in 1989, faecal specimens were collected from residents in villages and the town of Vellore in South India. Examination of the faecal specimens revealed that virtually the whole population carried commensal bacteria resistant to trimethoprim, ampicillin and chloramphenicol. Most specimens contained more than one type of bacterium resistant to each antibiotic. There was less resistance to nalidixic acid, with a higher proportion in the town (33%) than in the villages (13%). Although there was little cross-resistance of the ampicillin-resistant strains to later generation cephalosporins, 50% were resistant to the combination of amoxycillin and clavulanic acid. There was no significant cross-resistance of the nalidixic acid-resistant strains to fluorinated 4-quinolones, despite the free availability of ciprofloxacin and norfloxacin in the area. The probable reason for the high incidence of resistance to first generation antimicrobials is the extensive use of these agents, coupled with continuous exposure to large numbers of faecal micro-organisms. PMID:1607330

  13. Antibiotic prescription behaviours in Lao People's Democratic Republic: a knowledge, attitude and practice survey

    PubMed Central

    Quet, Fabrice; Leyer, Caroline; Buisson, Yves; Newton, Paul N; Naphayvong, Philaysak; Keoluangkhot, Valy; Chomarat, Monique; Longuet, Christophe; Steenkeste, Nicolas; Jacobs, Jan

    2015-01-01

    Abstract Objective To assess the antibiotic prescribing practices of doctors working in the Lao People's Democratic Republic and their knowledge of local antibiotic resistance patterns. Methods Doctors attending morning meetings in 25 public hospitals in four provinces were asked to complete a knowledge, attitude and practice survey. The questionnaire contained 43 multiple choice questions that the doctor answered at the time of the meeting. Findings The response rate was 83.4% (386/463). Two hundred and seventy doctors (59.8%) declared that they had insufficient information about antibiotics. Only 14.0% (54/386) recognized the possibility of cephalosporin cross-resistance in methicillin-resistant Staphylococcus aureus. Most participants had no information about local antibiotic resistance for Salmonella Typhi (211/385, 54.8%) and hospital-acquired pneumonia (253/384, 65.9%). Unnecessary antibiotic prescriptions were considered as harmless by 115 participants and 148 considered locally-available generic antibiotics to be of poor quality. Nearly three-quarters (280/386) of participants agreed that it was difficult to select the correct antibiotics. Most participants (373/386) welcomed educational programmes on antibiotic prescribing and 65.0% (249/383) preferred local over international antibiotic guidelines. Conclusion Doctors in the Lao People's Democratic Republic seem to favour antibiotic prescribing interventions. Health authorities should consider a capacity building programme that incorporates antibiotic prescribing and hospital infection control. PMID:26229186

  14. Evaluation of active designs of cephalosporin C acylase by molecular dynamics simulation and molecular docking.

    PubMed

    Li, Qing; Huang, Xiaoqiang; Zhu, Yushan

    2014-07-01

    Optimization to identify the global minimum energy conformation sequence in in silico enzyme design is computationally non-deterministic polynomial-time (NP)-hard, with the search time growing exponentially as the number of design sites increases. This drawback forces the modeling of protein-ligand systems to adopt discrete amino acid rotamers and ligand conformers, as well as continuum solvent treatment of the environment; however, such compromises produce large numbers of false positives in sequence selection. In this report, cephalosporin acylase, which catalyzes the hydrolytic reaction of cephalosporin C to 7-aminocephalosporanic acid, was used to investigate the dynamic features of active-site-transition-state complex structures using molecular dynamics (MD) simulations to potentially eliminate false positives. The molecular docking between cephalosporin C and wild type acylase N176 and its eight mutants showed that the rate-limiting step in the hydrolytic reaction of cephalosporin C is the acylation process. MD simulations of the active-site-transition-state complex structures of the acylation processes for N176 and its eight mutants showed that the geometrical constraints between catalytic residues and small molecule transition states are always well maintained during the 20ns simulation for mutants with higher activities, and more hydrogen bonds between binding residues and functional groups of the ligand side chain in the active pocket are formed for mutants with higher activities. The conformations of the ligand transition states were changed greatly after the simulation. This indicates that the hydrogen bond network between the ligand and protein could be improved to enhance the activity of cephalosporin C acylase in subsequent design. PMID:24935111

  15. Heterologous Production of the Marine Myxobacterial Antibiotic Haliangicin and Its Unnatural Analogues Generated by Engineering of the Biochemical Pathway

    PubMed Central

    Sun, Yuwei; Feng, Zhiyang; Tomura, Tomohiko; Suzuki, Akira; Miyano, Seishi; Tsuge, Takashi; Mori, Hitoshi; Suh, Joo-Won; Iizuka, Takashi; Fudou, Ryosuke; Ojika, Makoto

    2016-01-01

    Despite their fastidious nature, marine myxobacteria have considerable genetic potential to produce novel secondary metabolites. The marine myxobacterium Haliangium ochraceum SMP-2 produces the antifungal polyketide haliangicin (1), but its productivity is unsatisfactory. The biosynthetic gene cluster hli (47.8 kbp) associated with 1 was identified and heterologously expressed in Myxococcus xanthus to permit the production of 1 with high efficiency (tenfold greater amount and threefold faster in growth speed compared with the original producer), as well as the generation of bioactive unnatural analogues of 1 through gene manipulation. A unique acyl-CoA dehydrogenase was found to catalyse an unusual γ,δ-dehydrogenation of the diketide starter unit, leading to the formation of the terminal alkene moiety of 1. Biological evaluation of the analogues obtained through this study revealed that their bioactivities (anti-oomycete and cytotoxic activities) can be modified by manipulating the vinyl epoxide at the terminus opposite the β-methoxyacrylate pharmacophore. PMID:26915413

  16. Heterologous Production of the Marine Myxobacterial Antibiotic Haliangicin and Its Unnatural Analogues Generated by Engineering of the Biochemical Pathway.

    PubMed

    Sun, Yuwei; Feng, Zhiyang; Tomura, Tomohiko; Suzuki, Akira; Miyano, Seishi; Tsuge, Takashi; Mori, Hitoshi; Suh, Joo-Won; Iizuka, Takashi; Fudou, Ryosuke; Ojika, Makoto

    2016-01-01

    Despite their fastidious nature, marine myxobacteria have considerable genetic potential to produce novel secondary metabolites. The marine myxobacterium Haliangium ochraceum SMP-2 produces the antifungal polyketide haliangicin (1), but its productivity is unsatisfactory. The biosynthetic gene cluster hli (47.8?kbp) associated with 1 was identified and heterologously expressed in Myxococcus xanthus to permit the production of 1 with high efficiency (tenfold greater amount and threefold faster in growth speed compared with the original producer), as well as the generation of bioactive unnatural analogues of 1 through gene manipulation. A unique acyl-CoA dehydrogenase was found to catalyse an unusual ?,?-dehydrogenation of the diketide starter unit, leading to the formation of the terminal alkene moiety of 1. Biological evaluation of the analogues obtained through this study revealed that their bioactivities (anti-oomycete and cytotoxic activities) can be modified by manipulating the vinyl epoxide at the terminus opposite the ?-methoxyacrylate pharmacophore. PMID:26915413

  17. Effect of incubation temperature and time on the precision of data generated by antibiotic disc diffusion assays.

    PubMed

    Smith, P; Kronvall, G

    2015-07-01

    The influence on the precision of disc diffusion data of the conditions under which the tests were performed was examined by analysing multilaboratory data sets generated after incubation at 35C for 18h, at 28C for 24h and 22C for 24h and 48h. Analyses of these data sets demonstrated that precision was significantly and progressively decreased as the test temperature was reduced from 35 to 22C. Analysis of the data obtained at 22C also showed the precision was inversely related to the time of incubation. Temperature and time related decreases in precision were not related to differences in the mean zone sizes of the data sets obtained under these test conditions. Analysis of the zone data obtained at 28 and 22C as single laboratory sets demonstrated that reductions of incubation temperature resulted in significant increases in both intralaboratory and interlaboratory variation. Increases in incubation time at 22C were, however, associated with statistically significant increases in interlaboratory variation but not with any significant increase in intralaboratory variation. The significance of these observations for the establishment of the acceptable limits of precision of data sets that can be used for the setting of valid epidemiological cut-off values is discussed. PMID:25074782

  18. Ceftobiprole: a review of a broad-spectrum and anti-MRSA cephalosporin.

    PubMed

    Zhanel, George G; Lam, Ashley; Schweizer, Frank; Thomson, Kristjan; Walkty, Andrew; Rubinstein, Ethan; Gin, Alfred S; Hoban, Daryl J; Noreddin, Ayman M; Karlowsky, James A

    2008-01-01

    Ceftobiprole, an investigational cephalosporin, is currently in phase III clinical development. Ceftobiprole is a broad-spectrum cephalosporin with demonstrated in vitro activity against Gram-positive cocci, including meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant S. epidermidis, penicillin-resistant S. pneumoniae, Enterococcus faecalis, Gram-negative bacilli including AmpC-producing Escherichia coli and Pseudomonas aeruginosa, but excluding extended-spectrum beta-lactamase-producing strains. Like cefotaxime, ceftriaxone, ceftazidime, and cefepime, ceftobiprole demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. In single-step and serial passage in vitro resistance development studies, ceftobiprole demonstrated a low propensity to select for resistant subpopulations. Ceftobiprole, like cefepime, is a weak inducer and a poor substrate for AmpC beta-lactamases.Ceftobiprole medocaril, the prodrug of ceftobiprole, is converted by plasma esterases to ceftobiprole in <30 minutes. Peak serum concentrations of ceftobiprole observed at the end of a single 30-minute infusion were 35.5 mug/mL for a 500-mg dose and 59.6 mug/mL for a 750-mg dose. The volume of distribution of ceftobiprole is 0.26 L/kg ( approximately 18 L), protein binding is 16%, and its serum half-life is approximately 3.5 hours. Ceftobiprole is renally excreted ( approximately 70% in the active form) and systemic clearance correlates with creatinine clearance, meaning that dosage adjustment is required in patients with renal dysfunction. Ceftobiprole has a modest post-antibiotic effect (PAE) of approximately 0.5 hours for MRSA and a longer PAE of approximately 2 hours for penicillin-resistant pneumococci. Ceftobiprole, when administered intravenously at 500 mg once every 8 hours (2-hour infusion), has a >90% probability of achieving f T(>MIC) (free drug concentration exceeds the minimum inhibitory concentration [MIC]) for 40% and 60%, respectively, of the dosing interval for isolates with ceftobiprole MIC < or =4 and < or =2 mg/L, respectively.Currently, only limited clinical trial data are published for ceftobiprole. In a phase III trial, 784 patients with Gram-positive skin infections were randomized to treatment with either ceftobiprole 500 mg or vancomycin 1 g, each administered twice daily for 7-14 days; 93.3% of patients were clinically cured with ceftobiprole compared with 93.5% receiving vancomycin, and the eradication rate for MRSA infections was 91.8% for ceftobiprole compared with 90% for vancomycin. A phase III, randomized, double-blind, multicenter trial compared ceftobiprole 500 mg every 8 hours with vancomycin 1 g every 12 hours plus ceftazidime 1 g every 8 hours in patients with complicated skin and skin structure infections. Of the 828 patients enrolled, 31% had diabetic foot infections, 30% had abscesses, and 22% had wounds. No difference in clinical cure was reported in the clinically evaluable, intent-to-treat and microbiologically evaluable populations with cure rates of 90.5%, 81.9%, and 90.8%, respectively, in the ceftobiprole-treated patients and 90.2%, 80.8%, and 90.5%, respectively, in the vancomycin plus ceftazidime-treated group. Microbiologic eradication of Gram-positive cocci meticillin-susceptible S. aureus (MSSA) [ceftobiprole 91% vs vancomycin plus ceftazidime 92%] and MRSA (ceftobiprole 87% vs vancomycin plus ceftazidime 80%), as well as Gram-negative bacilli, E. coli (ceftobiprole 89% vs vancomycin plus ceftazidime 92%), and P. aeruginosa (ceftobiprole 87% vs vancomycin plus ceftazidime 100%), was not significantly different between groups. Similar cures rates in the microbiologically evaluable population occurred in both groups for Panton-Valentine leukocidin (PVL)-positive MSSA and PVL-positive MRSA.Currently, ceftobiprole has completed phase III trials for complicated skin and skin structure infections due to MRSA and nosocomial pneumonia due to suspected or proven MRSA; phase III trials are also ongoing in community-acquired pneumonia. Ceftobiprole has so far demonstrated a good safety profile in preliminary studies with similar tolerability to comparators. The broad-spectrum activity of ceftobiprole may allow it to be used as monotherapy in situations where a combination of antibacterials might be required. Further clinical studies are needed to determine the efficacy and safety of ceftobiprole and to define its role in patient care. PMID:18572975

  19. Non-Phenotypic Tests to Detect and Characterize Antibiotic Resistance Mechanisms in Enterobacteriaceae

    PubMed Central

    Lupo, Agnese; Papp-Wallace, Krisztina M.; Sendi, Parham; Bonomo, Robert A.; Endimiani, Andrea

    2014-01-01

    In the past two decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum β-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDITOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed. PMID:24091103

  20. Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms in Enterobacteriaceae.

    PubMed

    Lupo, Agnese; Papp-Wallace, Krisztina M; Sendi, Parham; Bonomo, Robert A; Endimiani, Andrea

    2013-11-01

    In the past 2 decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum β-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDI-TOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed. PMID:24091103

  1. Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters.

    PubMed

    Leonard, Anne F C; Zhang, Lihong; Balfour, Andrew J; Garside, Ruth; Gaze, William H

    2015-09-01

    Infections caused by antibiotic resistant bacteria (ARB) are associated with poor health outcomes and are recognised globally as a serious health problem. Much research has been conducted on the transmission of ARB to humans. Yet the role the natural environment plays in the spread of ARB and antibiotic resistance genes is not well understood. Antibiotic resistant bacteria have been detected in natural aquatic environments, and ingestion of seawater during water sports is one route by which many people could be directly exposed. The aim was to estimate the prevalence of resistance to one clinically important class of antibiotics (third-generation cephalosporins (3GCs)) amongst Escherichia coli in coastal surface waters in England and Wales. Prevalence data was used to quantify ingestion of 3GC-resistant E. coli (3GCREC) by people participating in water sports in designated coastal bathing waters. A further aim was to use this value to derive a population-level estimate of exposure to these bacteria during recreational use of coastal waters in 2012. The prevalence of 3GC-resistance amongst E. coli isolated from coastal surface waters was estimated using culture-based methods. This was combined with the density of E. coli reported in designated coastal bathing waters along with estimations of the volumes of water ingested during various water sports reported in the literature to calculate the mean number of 3GCREC ingested during different water sports. 0.12% of E. coli isolated from surface waters were resistant to 3GCs. This value was used to estimate that in England and Wales over 6.3 million water sport sessions occurred in 2012 that resulted in the ingestion of at least one 3GCREC. Despite the low prevalence of resistance to 3GCs amongst E. coli in surface waters, there is an identifiable human exposure risk for water users, which varies with the type of water sport undertaken. The relative importance of this exposure is likely to be greater in areas where a large proportion of the population enjoys water sports. Millions of water sport sessions occurred in 2012 that were likely to have resulted in people ingesting E. coli resistant to a single class of antibiotics (3GCs). However, this is expected to be a significant underestimate of recreational exposure to all ARB in seawater. This is the first study to use volumes of water ingested during different water sports to estimate human exposure to ARB. Further work needs to be done to elucidate the health implications and clinical relevance of exposure to ARB in both marine and fresh waters in order to fully understand the risk to public health. PMID:25832996

  2. Alteration of substrate selection of antibiotic acylase from ?-lactam to echinocandin.

    PubMed

    Isogai, Yasuhiro; Nakayama, Kazuki

    2016-02-01

    The antibiotic acylases belonging to the N-terminal nucleophile hydrolase superfamily are key enzymes for the industrial production of antibiotic drugs. Cephalosporin acylase (CA) and penicillin G acylase (PGA) are two of the most intensively studied enzymes that catalyze the deacylation of ?-lactam antibiotics. On the other hand, aculeacin A acylase (AAC) is known to be an alternative acylase class catalyzing the deacylation of echinocandin or cyclic lipopeptide antibiotic compounds, but its structural and enzymatic properties remain to be explored. In the present study, 3D homology models of AAC were constructed, and docking simulation with substrate ligands was performed for AAC, as well as for CA and PGA. The docking models of AAC with aculeacin A suggest that AAC has the deep narrow binding pocket for the long-chain fatty acyl group of the echinocandin molecule. To confirm this, CA mutants have been designed to form the binding pocket for the long acyl chain. Experimentally synthesized mutant enzymes exhibited lower enzymatic activity for cephalosporin but higher activity for aculeacin A, in comparison with the wild-type enzyme. The present results have clarified the difference in mechanisms of substrate selection between the ?-lactam and echinocandin acylases and demonstrate the usefulness of the computational approaches for engineering the enzymatic properties of antibiotic acylases. PMID:26590167

  3. Inhaled antibiotics: dry or wet?

    PubMed

    Tiddens, Harm A W M; Bos, Aukje C; Mouton, Johan W; Devadason, Sunalene; Janssens, Hettie M

    2014-11-01

    Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching. In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed. PMID:25323242

  4. [Looking for the new preparations for antibacterial therapy. I. New antibiotics and chemotherapeutics on the market].

    PubMed

    Karpiuk, Izabela; Tyski, Stefan

    2012-01-01

    Development of new mechanisms of resistance and relatively easy and fast transferring of resistance genes between cells have resulted in emergence of large number of multi-drug resistant bacteria in recent years. Therefore, it is important to intensively search for new, effective compounds possessing antibacterial potential and apply them as active ingredients of medicinal products. This procedure may lead to eradication of clinically relevant, dangerous bacteria. In the twentyfirst century, three new classes of antibacterial agents: oxazolidinones, lipopeptides and pleuromutilins were introduced into the therapy. Compounds from the last group, such as tiamulin, were used previously, but only in veterinary. New 18 antimicrobial compounds, belonging to known therapeutic groups, have been registered since 2000. The largest group among antibacterial chemotherapeutics is quinolones. Group of natural compounds includes: new carbapenems, cephalosporins of V generation and other agents, like telithromycin, tigecycline, telavancin and fidaxomicin. This article is a part of the series associated with searching for new antibacterial agents and it relates to new antibiotics and antibacterial chemotherapeutics approved for the world-wide market since 2000. The next parts of this cycle will be devoted to compounds ongoing the clinical trials. PMID:23484382

  5. Impact of the New Delhi metallo-beta-lactamase on beta-lactam antibiotics

    PubMed Central

    Zmarlicka, Monika T; Nailor, Michael D; Nicolau, David P

    2015-01-01

    Since the first New Delhi metallo-beta-lactamase (NDM) report in 2009, NDM has spread globally causing various types of infections. NDM-positive organisms produce in vitro resistance phenotypes to carbapenems and many other antimicrobials. It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes. There are many instances where good clinical outcomes are described, despite a mismatch between administered antimicrobials and resistant in vitro susceptibilities. Available in vitro data for either monotherapy or combination therapy does not provide an explanation for these observations. However, animal studies do begin to shed more light on this phenomenon. They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype. As such, previously abandoned therapies, particularly carbapenems and beta-lactamase inhibitor combinations, may retain utility against infections caused by NDM producers. PMID:26345624

  6. Quantitative determination of some thiazole cephalosporins through complexation with palladium (II) chloride.

    PubMed

    Fattah, A; El-Walily, M; Gazy, A A; Belal, S F; Khamis, E F

    2000-03-01

    A simple and sensitive spectrophotometric method has been developed for the determination of five cephalosporins namely cefpodoxime (CFPD), ceftizoxime (CTIZ), ceftazidime (CZD), ceftriaxone (CTRX), and cefixime (CXIM). This method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulphate (SLS) as surfactant. The reaction conditions were studied and optimized. The procedure was validated. For each drug, the composition of this complex as well as its stability constant were also investigated. The proposed method was used for the determination of the above-mentioned drugs in their commercial preparations. The results were compared statistically with either official or published methods and showed no significant difference between the two methods. PMID:10719922

  7. A novel sensor for cephalosporins based on electrocatalytic oxidation by poly(o-anisidine)/SDS/Ni modified carbon paste electrode.

    PubMed

    Ojani, Reza; Raoof, Jahan-Bakhsh; Zamani, Saeed

    2010-06-15

    In this work for first time, the electrocatalytic oxidations of some cephalosporins were carried out by poly(o-anisidine)/SDS/Ni modified carbon paste electrode using cyclic voltammetry, chronoamperometry and chronocoulometry methods. At first, poly(o-anisidine) was formed by cyclic voltammetry in monomer solution containing sodium dodesyl sulfate (SDS), on carbon paste electrode surface. Then, Ni(II) ions were incorporated to electrode by immersion of the polymeric modified electrode having amine group in 0.1molL(-1) Ni(II) ion solution. A good redox behavior was observed for the Ni(OH)(2)/NiOOH couple on the surface of this electrode. Cephalosporins were successfully oxidized on the surface of this nickel ions dispersed poly(o-anisidine) modified carbon paste electrode. The electrocatalytic oxidation peak currents of cephalosporins were linearly dependent on their concentration. Electrode was successfully applied to determine cephalosporins in pharmaceutical preparations. PMID:20441933

  8. Spectrophotometric complexation of cephalosporins with palladium (II) chloride in aqueous and non-aqueous solvents

    NASA Astrophysics Data System (ADS)

    Bagheri Gh., A.; Yosefi rad, A.; Rezvani, M.; Roshanzamir, S.

    2012-04-01

    The complexation reaction of cephalosporins namely cefotaxime (CTX), cefuroxime (CRX), and cefazolin (CEFAZ) with palladium (II) ions have been studied in water and DMF in 25 C by the spectrophotometric methods. The method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulfate (SLS) as surfactant. The complexation process was optimized in terms of pH, temperature and contact time. The stoichiometry of all the complexes was found to be 2:1 (metal ion/ligand) for CTX, CRX, and 1:2 for CEFAZ. The stoichiometry of palladium (II)-cephalosporins was estimated by mole ratio and continuous variation methods and emphasized by the KINFIT program. These drugs could be determined by measuring the absorbance of each complex at its specific ?max. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms.

  9. Spectrophotometric complexation of cephalosporins with palladium (II) chloride in aqueous and non-aqueous solvents.

    PubMed

    Bagheri Gh, A; Yosefi rad, A; Rezvani, M; Roshanzamir, S

    2012-04-01

    The complexation reaction of cephalosporins namely cefotaxime (CTX), cefuroxime (CRX), and cefazolin (CEFAZ) with palladium (II) ions have been studied in water and DMF in 25 °C by the spectrophotometric methods. The method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulfate (SLS) as surfactant. The complexation process was optimized in terms of pH, temperature and contact time. The stoichiometry of all the complexes was found to be 2:1 (metal ion/ligand) for CTX, CRX, and 1:2 for CEFAZ. The stoichiometry of palladium (II)-cephalosporins was estimated by mole ratio and continuous variation methods and emphasized by the KINFIT program. These drugs could be determined by measuring the absorbance of each complex at its specific λmax. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms. PMID:22286057

  10. Antibiotic resistance: An ethical challenge.

    PubMed

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper. PMID:26242553

  11. Determination of solid-state acidity of chitin-metal silicates and their effect on the degradation of cephalosporin antibiotics.

    PubMed

    Gana, Fatima Zohra; Rashid, Iyad; Badwan, Adnan; Alkhamis, Khouloud A

    2012-07-01

    It was of interest to determine the solid-state acidity of chitin-metal silicate coprocessed excipients and to correlate this acidity to the chemical stability of cefotaxime sodium in the presence of the aforementioned excipients. The solid-state acidities of chitin aluminum silicate, chitin magnesium silicate, and chitin calcium silicate were determined by reflectance spectroscopy using structurally different dye molecules. The chemical stability of cefotaxime sodium was assessed at 50 °C in a 4% (w/v) slurry system in the pH range 6.6-10.5 and in the solid-state in the Hammett acidity range 6.1-7.8. The solid-state acidity was found to be reproducible because one or more structurally different dye molecules gave reliable solid-state acidity values. A significant discrepancy in pH stability profile of cefotaxime sodium between the solid-state and the slurry system was observed. Furthermore, chitin aluminum silicate showed minimum drug stability in the solid-state, close to where the maximum drug stability in the slurry was observed. This unexpected effect might be ascribed to the catalytic properties of chitin aluminum silicate. The slurry method was not able to predict efficiently the solid-state surface acidity and stability of cefotaxime sodium. Moreover, the solid-state chemical stability might be influenced by factors other than the solid-state acidity. PMID:22499263

  12. Potentiality of yeast Candida sp. SMN04 for degradation of cefdinir, a cephalosporin antibiotic: kinetics, enzyme analysis and biodegradation pathway.

    PubMed

    Selvi, A; Das, Devlina; Das, Nilanjana

    2015-12-01

    A new yeast strain isolated from the pharmaceutical wastewater was capable of utilizing cefdinir as a sole carbon source for their growth in mineral medium. The yeast was identified and named as Candida sp. SMN04 based on morphology and 18S-ITS-D1/D2/D3 rRNA sequence analysis. The interaction between factors pH (3.0-9.0), inoculum dosage (1-7%), time (1-11 day) and cefdinir concentration (50-450?mg/L) was studied using a Box-Behnken design. The factors were studied as a result of their effect on cell dry weight (R1; g/L), extended spectrum ?-lactamase (ESBL) assay (R2; mm), P450 activity (R3; U/mL) and degradation (R4; %). Maximum values of R1, R2, R3 and R4 were obtained at central values of all the parameters. The isolated yeast strain efficiently degraded 84% of 250?mg?L(-1) of cefdinir within 6 days with a half-life of 2.97 days and degradation rate constant of 0.2335 per day. Pseudo-first-order model efficiently described the process. Among the various enzymes tested, the order of activity at the end of Day 4 was noted to be: cytochrome P450 (1.76??0.03)?>?NADPH reductase (1.51??0.20)?>?manganese peroxidase and amylase (0.66??0.15; 0.66??0.70). Intermediates were successfully characterized by liquid chromatography-mass spectrometry. The opening of the ?-lactam ring involving ESBL activity was considered as one of the major steps in the cefdinir degradation process. Fourier transform-infrared spectroscopy analysis showed the absence of spectral vibrations between 1766 and 1519?cm(-1) confirming the complete removal of lactam ring during cefdinir degradation. The results of the present study are promising for the use of isolated yeast Candida sp. SMN04 as a potential bioremediation agent. PMID:26000889

  13. Antimicrobial metallopolymers and their bioconjugates with conventional antibiotics against multidrug-resistant bacteria.

    PubMed

    Zhang, Jiuyang; Chen, Yung Pin; Miller, Kristen P; Ganewatta, Mitra S; Bam, Marpe; Yan, Yi; Nagarkatti, Mitzi; Decho, Alan W; Tang, Chuanbing

    2014-04-01

    Bacteria are now becoming more resistant to most conventional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA), a complex of multidrug-resistant Gram-positive bacterial strains, has proven especially problematic in both hospital and community settings by deactivating conventional β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, through various mechanisms, resulting in increased mortality rates and hospitalization costs. Here we introduce a class of charged metallopolymers that exhibit synergistic effects against MRSA by efficiently inhibiting activity of β-lactamase and effectively lysing bacterial cells. Various conventional β-lactam antibiotics, including penicillin-G, amoxicillin, ampicillin, and cefazolin, are protected from β-lactamase hydrolysis via the formation of unique ion-pairs between their carboxylate anions and cationic cobaltocenium moieties. These discoveries could provide a new pathway for designing macromolecular scaffolds to regenerate vitality of conventional antibiotics to kill multidrug-resistant bacteria and superbugs. PMID:24628053

  14. In Vitro Antibiotic Susceptibilities of Yersinia pestis Determined by Broth Microdilution following CLSI Methods

    PubMed Central

    Hershfield, Jeremy; Marchand, Charles; Miller, Lynda; Halasohoris, Stephanie; Purcell, Bret K.; Worsham, Patricia L.

    2015-01-01

    In vitro susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of Yersinia pestis by the broth microdilution method at two temperatures, 28C and 35C, following Clinical and Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, ?-lactams, cephalosporins, and carbapenems. Only a 1-well shift was observed for the majority of antibiotics between the two temperatures. Establishing and comparing antibiotic susceptibilities of a diverse but specific set of Y. pestis strains by standardized methods and establishing population ranges and MIC50 and MIC90 values provide reference information for assessing new antibiotic agents and also provide a baseline for use in monitoring any future emergence of resistance. PMID:25583720

  15. Antagonism of chemical genetic interaction networks resensitize MRSA to β-lactam antibiotics.

    PubMed

    Lee, Sang Ho; Jarantow, Lisa Wang; Wang, Hao; Sillaots, Susan; Cheng, Henry; Meredith, Timothy C; Thompson, John; Roemer, Terry

    2011-11-23

    Antibiotic drug resistance among hospital and community acquired methicillin resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current therapeutics. We describe a chemical genetic strategy using antisense interference to broadly identify new drug targets that potentiate the effects of existing antibiotics against both etiological classes of MRSA infection. Further, we describe the resulting chemical genetic interaction networks and highlight the prominent and overlapping target sets that restore MRSA susceptibility to penicillin, cephalosporins, and carbapenems. Pharmacological validation of this approach is the potent synergy between a known inhibitor to a member of this genetic potentiation network (GlmS) and a broad set of β-lactam antibiotics against methicillin resistant Staphylococci. Developing drug-like leads to these targets may serve as rational and effective combination agents when paired with existing β-lactam antibiotics to restore their efficacy against MRSA. PMID:22118672

  16. Precursor structure of cephalosporin acylase. Insights into autoproteolytic activation in a new N-terminal hydrolase family.

    PubMed

    Kim, Youngsoo; Kim, Sanggu; Earnest, Thomas N; Hol, Wim G J

    2002-01-25

    Autocatalytic proteolytic cleavage is a frequently observed post-translational modification in proteins. Cephalosporin acylase (CA) is a recently identified member of the N-terminal hydrolase family that is activated from an inactive precursor by autoproteolytic processing, generating a new N-terminal residue, which is either a Ser or a Thr. The N-terminal Ser or Thr becomes a nucleophilic catalytic center for intramolecular and intermolecular amide cleavages. The gene structure of the open reading frame of CAs generally consists of a signal peptide followed by the alpha-subunit, a spacer sequence, and the beta-subunit, which are all translated into a single polypeptide chain, the CA precursor. The precursor is post-translationally modified into an active heterodimeric enzyme with alpha- and beta-subunits, first by intramolecular cleavage and second by intermolecular cleavage. We solved the first CA precursor structure (code 1KEH) from a class I CA from Pseudomonas diminuta at a 2.5-A resolution that provides insight into the mechanism of intramolecular cleavage. A conserved water molecule, stabilized by four hydrogen bonds in unusual pseudotetrahedral geometry, plays a key role to assist the OG atom of Ser(1beta) to generate a strong nucleophile. In addition, the site of the secondary intermolecular cleavage of CA is proposed to be the carbonyl carbon of Gly(158alpha) (Kim, S., and Kim, Y., (2001) J. Biol. Chem., 276, 48376-48381), which is different from the situation in two other class I CAs. PMID:11706000

  17. [Sensitivity of "Haemophilus influenzae" to 5 antibiotics and rapid detection of its resistance to ampicilin (author's transl)].

    PubMed

    Piot, P; van DYCK, E; Pattyn, S R

    1977-02-01

    Sensitivity of Haemophilus influenzae to 5 antibiotics has been determined by the agar dilution method. Two strains out of 165 are resistant to ampicillin and 5% to tetracycline. All strains were sensitive to chloramphenicol, cotrimoxazole and cefuroxime. A simple test for rapid detection of beta-lactamase with a chromogenic cephalosporin and sensitivity testing by an agar diffusion method were evaluated for Haemophilus. PMID:322045

  18. Evaluation of separation and purification processes in the antibiotic industry

    SciTech Connect

    Bienkowski, P.R.; Lee, D.D.; Byers, C.H.

    1987-05-01

    The different separation and purification processes for three major types of antibiotics, Penicillins, Cephalosporins and Tetracyclines will be discussed. All antibiotic, processing plants contain two majors sections, a relatively small and highly specialized fermentation section and a very large (60-80% of the plant) separation and purification section. The fermentation sections for the different antibiotics are essentially identical, except for differences in growth media and operating variables, but there are vast differences in the separation and purification sections. Several different separation methods are used including filtration, ultrafiltration, centrifugation, precipitation, extraction, chromatography and various membrane methods. Variables affecting the specific separation and purification configurations include final fermentation broth concentration, by-product formed during fermentation, the physical properties and molecular structure of the various antibiotics and special purification requirements. Necessary reductions in the separation and purification processes required for rebuilding the antibiotic industry after a national emergency are discussed along with several relatively new separation/purification methods that hold great promise for effecting these reductions, chromatography, supercritical fluid extraction (SCF), and membranes. 35 refs., 10 figs., 2 tabs.

  19. Trends in Antibiotic Treatment of Acute Otitis Media and Treatment Failure in Children, 20002011

    PubMed Central

    McGrath, Leah J.; Becker-Dreps, Sylvia; Pate, Virginia; Brookhart, M. Alan

    2013-01-01

    Objectives Guidelines to treat acute otitis media (AOM) were published in 2004. Initial declines in prescribing were shown, but it's unknown if they were sustained. We examine trends in antibiotic dispensing patterns to treat AOM among a large population of children. We also document trends in antibiotic failure. Study Design Children aged 3 months to 12 years with an AOM diagnosis, enrolled in a commercial claims database between January 1, 2000-December 31, 2011 were included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic prescriptions. Antibiotic failure was defined as a dispensing of a different antibiotic class within 2-18 days after the first prescription. We analyzed trends in antibiotic use and failure by class of antibiotic and year. Results We identified over 4 million children under 13 years with AOM. The proportion of antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of dispensing rebounded to pre-guideline levels. However, levels began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%. Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic failure decreased slightly, and macrolides had the lowest proportion of failures, while all other classes had failure rates around 10%. Conclusions In recent years, antibiotic dispensing to treat AOM remains high. In addition, the use of broad-spectrum antibiotics is increasing despite having a high rate of treatment failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM treatment could lead to the development of antibiotic-resistant infections. PMID:24324680

  20. Antibiotic use in dairy herds in the Netherlands from 2005 to 2012.

    PubMed

    Kuipers, A; Koops, W J; Wemmenhove, H

    2016-02-01

    The aim of this study was to examine the variation in antibiotic use and the effects of external factors on trends in antibiotic use at the herd level by using the number of daily dosages as an indicator for antibiotic use. For this purpose, antibiotic use was analyzed in 94 dairy herds in the Netherlands from 2005 to 2012. The herds were divided into 3 groups of farmers: one group was guided in their antibiotic use from 2008 to 2010 as part of the project, whereas the other 2 groups were not actively guided. The farms were located in 10 of the 12 provinces and were clients of 32 of the 300 veterinary practices that treat cattle. Sales invoices from the veterinary practices provided the antibiotic and cost data for the participating farmers. The number of animal-defined daily dosages (ADDD) indicates the number of days per year that the average cow in a herd is given antibiotic treatment. The average ADDD for all farms from 2005 to 2012 was 5.86 (standard deviation=2.14); 68% of ADDD were used for udder health, 24% for clinical mastitis and 44% for dry-cow therapy. Variation in ADDD among herds decreased during the study period. The trend in ADDD can be described as having 3 phases: (1) a period of increasing use coinciding with little public concern about antibiotic use (2005-2007), (2) a period of growing awareness and stabilization of use (2007-2010), and (3) a period of decreasing use coinciding with increasing societal concerns (2010-2012). The greatest reduction in use was for drugs other than those used to treat the udder. Drug use for mastitis treatment fell considerably in the final year of the study period, whereas farmers were reluctant to reduce use for dry-cow therapy. Almost 40% of the herds were given less than 2.5 ADDD for dry-cow therapy, which is equivalent to 2.5 tubes per average cow in the herd, and 20% used more than 3 tubes per cow. Use of third- and fourth-generation cephalosporins and fluoroquinolones dropped from 18% of ADDD during 2005 to 2010 to 1% in 2012, with a shift toward penicillins and broad spectrum drugs. The ADDD was 22% lower in 2012 than 2007, the year of the highest usage. The decrease in ADDD over time varied between the 3 groups of farmers. During the second phase of the study, the guided group began to display a reduction in use, whereas the other groups only displayed a significant reduction in the third phase. The reduction in antibiotic use has resulted in lower veterinary costs per cow in recent years. PMID:26709178

  1. New antibiotics for antibiotic-resistant bacteria

    PubMed Central

    Stubbings, William

    2009-01-01

    The need for new antibiotics to effectively treat antibiotic-resistant infections remains unfulfilled. Despite the well-publicised concern over this issue, only two novel antibiotic classes have been introduced in the past 20 years alongside several new agents of existing classes. Accordingly, the current antibiotic armoury remains inadequate to meet the challenges posed by resistance today. More worryingly, there are very few new agents being developed that can be expected to replace existing antibiotics that succumb to the rising tide of resistance. PMID:20948644

  2. Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms.

    PubMed

    Angel Villegas, Natalia; Baronetti, Jos; Albesa, Ins; Etcheverra, Anala; Becerra, M Cecilia; Padola, Nora L; Paraje, M Gabriela

    2015-10-01

    Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, with the main virulence factor of this bacterium being its capacity to secrete Shiga toxins (Stxs). Therefore, the use of certain antibiotics for the treatment of this infection, which induces the liberation of Stxs, is controversial. Reactive oxygen and nitrogen species are also involved in the pathogenesis of different diseases. The purpose of this study was to analyze the effects of antibiotics on biofilms of STEC and the relationships between cellular stress and the release of Stx. To this end, biofilms of reference and clinical strains were treated with antibiotics (ciprofloxacin, fosfomycin and rifaximin) and the production of oxidants, the antioxidant defense system and toxin release were evaluated. Ciprofloxacin altered the prooxidant-antioxidant balance, with a decrease of oxidant metabolites and an increase of superoxide dismutase and catalase activity, being associated with high-levels of Stx production. Furthermore, inhibition of oxidative stress by exogenous antioxidants was correlated with a reduction in the liberation of Stx, indicating the participation of this phenomenon in the release of this toxin. In contrast, fosfomycin and rifaximin produced less alteration with a minimal production of Stx. Our data show that treatment of biofilm-STEC with these antibiotics induces oxidative stress-mediated release of Stx. PMID:26130220

  3. Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data

    PubMed Central

    2013-01-01

    Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporins decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energys values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps. PMID:23594763

  4. The effect of past antibiotic exposure on diabetes risk

    PubMed Central

    Boursi, Ben; Mamtani, Ronac; Haynes, Kevin; Yang, Yu-Xiao

    2015-01-01

    Objective Gut microbiota influence metabolic pathways relevant to the pathogenesis of obesity, insulin-resistance and diabetes. Antibiotic therapy can alter the microbiota and is commonly used in western countries. We sought to evaluate whether past antibiotic exposure increases diabetes risk. Research design and methods We conducted a nested case-control study using a large population-based database from the United Kingdom (UK). Cases were defined as those with incident diagnosis of diabetes. For every case, 4 eligible controls matched on age, sex, practice-site, and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The risk was adjusted for body mass index (BMI), smoking, last glucose level and number of infections before index-date, as well as past medical history of coronary artery disease and hyperlipidemia. Results The study included 208,002 diabetic cases and 815,576 matched controls. Exposure to a single antibiotic prescription was not associated with higher adjusted diabetes risk. Treatment with 2–5 antibiotic courses was associated with increase in diabetic risk for penicillin, cephalosporins, macrolides and quinolones with adjusted OR ranging from 1.08 (95%CI 1.05–1.11) for penicillin to 1.15 (95%CI 1.08–1.23) for quinolones. The risk increased with the number of antibiotic courses and reached 1.37 (95%CI 1.19–1.58) for >5 courses of quinolones. There was no association between exposure to anti-virals and anti-fungals and diabetes risk. Conclusions Exposure to certain antibiotic groups increases diabetes risk. PMID:25805893

  5. Antibiotic prescription in intensive care units in Latin America.

    PubMed

    Curcio, Daniel J

    2011-01-01

    The intensive care units (ICUs) are often considered as the epicenters of antibiotic resistance. Therefore, the total antibiotic consumption is approximately ten fold greater in ICU wards than in general hospital wards. The aim of this study was to evaluate the current use of antibiotics in Latin American ICUs. Three cross-sectional (one-day point) prevalence studies were undertaken in 43 Latin American ICUs. Of 1644 patients admitted, 688 received antibiotic treatment on the days of the study (41.8 %) and, 392 cases (57 %) were due to nosocomial-acquired infections. Of all infections, 22 % (151/688) corresponded to septic shock; and 22 % (151/688) to nosocomial pneumonia (50/151 [33 %], ventilator-associated pneumonia). In 485 patients (70.5 %), cultures were performed before starting antibiotic treatment. The most common microorganisms isolated were extended-spectrum ß-lactamase Enterobacteriaceae, (30.5 %), and Pseudomonas aeruginosa (17 %). Carbapenems (imipenem or meropenem) were the antibiotics most frequently prescribed (151/688, 22 %), followed by vancomycin (103/688, 15 %), piperacillin-tazobactam (86/688, 12.5 %) and broad-spectrum cephalosporins (mainly cefepime) (83/688, 12 %). In summary, carbapenems were the most frequent antibiotics prescribed in Latin American ICUs. This practice seems justified for the high rates of ESBL-producing Gram-negatives found in our patients. Beyond this reason, the problem of bacterial resistance in LA requires that physicians improve the use of carbapenems. The high prevalence of carbapenem-resistant A. baumannii and P. aeruginosa in the region, along with the prevalence of carbapenem-resistant Enterobacteriaceae, have increased markedly. A comprehensive evidence-based stewardship program based on local antimicrobial use and resistance problems should be implemented in our clinical settings. PMID:22430995

  6. Genomic tools to profile antibiotic mode of action.

    PubMed

    Cardona, Silvia T; Selin, Carrie; Gislason, April S

    2015-11-01

    The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation. PMID:24617440

  7. Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores

    NASA Astrophysics Data System (ADS)

    Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

    2002-07-01

    Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics. We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the -lactam antibiotics. With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel. Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific. Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates.

  8. Anaerobic digestion of antibiotic residue in combination with hydrothermal pretreatment for biogas.

    PubMed

    Zhang, Guangyi; Li, Chunxing; Ma, Dachao; Zhang, Zhikai; Xu, Guangwen

    2015-09-01

    Antibiotic residues are difficult to be treated or utilized because of their high water content and residual antibiotics. This article is devoted to investigating the possibility of biogas production from cephalosporin C residue (CPCAR), one typical type of antibiotic residues, via anaerobic digestion in combination with hydrothermal pretreatment (HTPT). The results from the bench-scale experiments showed that the combination of HTPT and anaerobic digestion can provide a viable way to convert CPCAR into biogas, and the biogas and methane yields reached 290 and 200 ml(g TS)(-1), respectively. This article further evaluated the proposed technology in terms of energy balance and technical feasibility based on theoretical calculation using the data from a pilot HTPT test. It was shown that the process is totally self-sufficient in energy and its main challenging problem of ammonia inhibition can be solved via ammonia stripping. PMID:26038331

  9. Stability-indicating spectrofluorometric method for the determination of some cephalosporin drugs via their degradation products.

    PubMed

    Mostafa, Nadia M; Abdel-Fattah, Laila; Weshahy, Soheir A; Hassan, Nagiba Y; Boltia, Shereen A

    2015-01-01

    A stability-indicating spectrofluorometric method was investigated for the determination of three cephalosporin drugs, namely, cefpodoxime proxetil (CPD), cefixime trihydrate (CFX), and cefepime hydrochloride (CPM), via their acid and alkali degradation products. The three drugs were determined via their acid degradation at 432, 422, and 435 nm using an excitation wavelength of 310, 330, and 307 nm for CPD, CFX, and CPM determination, respectively, and via their alkali degradation at 407, 411, and 405 nm using an excitation wavelength of 310, 305, and 297 nm for CPD, CFX, and CPM determination, respectively. Linearity was achieved in the ranges of 0.35-3.50, 0.4-4.0, and 0.3-3.0 ?g/mL for the acid degradation products of CPD, CFX, and CPM, respectively, and in ranges of 0.05-0.5, 0.1-1.0, and 0.08-0.80 ?g/mL for the alkali degradation products of CPD, CFX, and CPM, respectively. The method was validated for various parameters according to International Conference on Harmonization guidelines. The method was successfully applied for the determination of these cephalosporin drugs in pharmaceutical dosage forms with good accuracy and precision. The results obtained by the proposed spectrofluorometric method were compared with good agreement to the official HPLC method. PMID:25905742

  10. When Antibiotics Are Needed

    MedlinePLUS

    ... fullstory_155797.html When Antibiotics Are Needed 'Get Smart' tips from an expert to prevent their overuse ... to combat the problem, the eighth annual "Get Smart About Antibiotics Week" is being sponsored by the ...

  11. Antibiotics and Resistance: Glossary

    MedlinePLUS

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network ...

  12. Combating Antibiotic Resistance

    MedlinePLUS

    ... For Consumers Home For Consumers Consumer Updates Combating Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... however, have contributed to a phenomenon known as antibiotic resistance. This resistance develops when potentially harmful bacteria change ...

  13. Antibiotic susceptibility profile of bacilli isolated from the skin of healthy humans

    PubMed Central

    Tarale, Prashant; Gawande, Sonali; Jambhulkar, Vinay

    2015-01-01

    Abstract In the present work, twelve bacilli were isolated from four different regions of human skin from Bela population of Nagpur district, India. The isolated bacilli were identified by their morphological, cultural and biochemical characteristics. Seven isolates were Gram negative rods, out of which five were belong to genus Pseudomonas. Three among the five Gram positive isolates were identified as Dermabactor and the remaining two Bacillus. Their antimicrobial susceptibility profile was determined by Kirby-Bauer disc diffusion method. The isolates showed resistance to several currently used broad-spectrum antibiotics. The Dermabactor genus was resistant to vancomycin, although it was earlier reported to be susceptible. Imipenem was found to be the most effective antibiotic for Pseudomonas while nalidixic acid, ampicillin and tetracycline were ineffective. Isolates of Bacillus displayed resistance to the extended spectrum antibiotics cephalosporin and ceftazidime. Imipenem, carbenicillin and ticarcillin were found to be the most effective antibiotics as all the investigated isolates were susceptible to them. Antibiotic resistance may be due to the overuse or misuse of antibiotics during the treatment, or following constant exposure to antibiotic-containing cosmetic formulations. PMID:26691469

  14. Role of pleiotropy during adaptation of TEM-1 β-lactamase to two novel antibiotics

    PubMed Central

    Schenk, Martijn F; Witte, Sariette; Salverda, Merijn L M; Koopmanschap, Bertha; Krug, Joachim; de Visser, J Arjan G M

    2015-01-01

    Pleiotropy is a key feature of the genotype–phenotype map, and its form and extent have many evolutionary implications, including for the dynamics of adaptation and the evolution of specialization. Similarly, pleiotropic effects of antibiotic resistance mutations may affect the evolution of antibiotic resistance in the simultaneous or fluctuating presence of different antibiotics. Here, we study the role of pleiotropy during the in vitro adaptation of the enzyme TEM-1 β-lactamase to two novel antibiotics, cefotaxime (CTX) and ceftazidime (CAZ). We subject replicate lines for four rounds of evolution to selection with CTX and CAZ alone, and in their combined and fluctuating presence. Evolved alleles show positive correlated responses when selecting with single antibiotics. Nevertheless, pleiotropic constraints are apparent from the effects of single mutations and from selected alleles showing smaller correlated than direct responses and smaller responses after simultaneous and fluctuating selection with both than with single antibiotics. We speculate that these constraints result from structural changes in the oxyanion pocket surrounding the active site, where accommodation of CTX and the larger CAZ is balanced against their positioning with respect to the active site. Our findings suggest limited benefits from the combined or fluctuating application of these related cephalosporins for containing antibiotic resistance. PMID:25861383

  15. Antibiotic susceptibility profile of bacilli isolated from the skin of healthy humans.

    PubMed

    Tarale, Prashant; Gawande, Sonali; Jambhulkar, Vinay

    2015-12-01

    In the present work, twelve bacilli were isolated from four different regions of human skin from Bela population of Nagpur district, India. The isolated bacilli were identified by their morphological, cultural and biochemical characteristics. Seven isolates were Gram negative rods, out of which five were belong to genus Pseudomonas. Three among the five Gram positive isolates were identified as Dermabactor and the remaining two Bacillus. Their antimicrobial susceptibility profile was determined by Kirby-Bauer disc diffusion method. The isolates showed resistance to several currently used broad-spectrum antibiotics. The Dermabactor genus was resistant to vancomycin, although it was earlier reported to be susceptible. Imipenem was found to be the most effective antibiotic for Pseudomonas while nalidixic acid, ampicillin and tetracycline were ineffective. Isolates of Bacillus displayed resistance to the extended spectrum antibiotics cephalosporin and ceftazidime. Imipenem, carbenicillin and ticarcillin were found to be the most effective antibiotics as all the investigated isolates were susceptible to them. Antibiotic resistance may be due to the overuse or misuse of antibiotics during the treatment, or following constant exposure to antibiotic-containing cosmetic formulations. PMID:26691469

  16. Reversibility of antibiotic resistance

    PubMed Central

    2014-01-01

    Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

  17. A colorimetric assay for the determination of acetyl xylan esterase or cephalosporin C acetyl esterase activities using 7-amino cephalosporanic acid, cephalosporin C, or acetylated xylan as substrate.

    PubMed

    Martnez-Martnez, Irene; Montoro-Garca, Silvia; Lozada-Ramrez, Jos Daniel; Snchez-Ferrer, Alvaro; Garca-Carmona, Francisco

    2007-10-15

    A bromothymol blue-based colorimetric assay has been devised to screen for acetyl xylan esterase or cephalosporin C (CPC) deacetylase activities using 7-amino cephalosporanic acid (7-ACA), CPC, or acetylated xylan as substrate. These enzymes are not screened with their natural substrates because of the tedious procedures available previously. Acetyl xylan esterase from Bacillus pumilus CECT 5072 was cloned, expressed in Escherichia coli Rosetta (DE3), and characterized using this assay. Similar K(M) values for 7-ACA and CPC were obtained when compared with those described using HPLC methods. The assay is easy to perform and can be carried out in robotic high-throughput colorimetric devices normally used in directed evolution experiments. The assay allowed us to detect improvements in activity at a minimum of twofold with a very low coefficient of variance in 96-well plates. This method is significantly faster and more convenient to use than are known HPLC and pH-stat procedures. PMID:17651681

  18. Facts about Antibiotic Resistance

    MedlinePLUS

    ... LH. A national evaluation of antibiotic expenditures by healthcare setting in the United States, 2009. J Antimicrob Chemother . 2013;68(3):715- ... Comparison of prescription drug costs in the United States and the United Kingdom, Part 4: Antibiotics in ... Smart for Healthcare Get Smart: Know When Antibiotics Work on the ...

  19. Finding alternatives to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The spread of antibiotic-resistant pathogens requires new treatments. The availability of new antibiotics has severely declined, and so alternatives to antibiotics need to be considered in both animal agriculture and human medicine. Products for disease prevention are different than products for d...

  20. Neonatal septicaemia in Ilorin: bacterial pathogens and antibiotic sensitivity pattern.

    PubMed

    Mokuolu, A O; Jiya, N; Adesiyun, O O

    2002-06-01

    All cases of septicemia among neonates admitted to the neonatal intensive care unit of the University of Ilorin Teaching Hospital, Ilorin, Nigeria between Jan 1995 and Dec 1996 were studied. Our aims were (1) to assess the incidence and microbial epidemiology of neonatal sepsis, (2) to generate baseline data and necessary research question for a proposed study on predictors of neonatal sepsis in our centre. Microbiology records of patients with confirmed septicemia was reviewed. Each of these babies had a single venous blood sample from a peripheral vein taken under aseptic conditions and before commencement of antibiotics. The needed data were entered into a proforma. Of the 198 neonates screened for sepsis, there were 61 (30.8%) positive blood cultures. Twenty-nine (48%) of these were inborn. The total number of live births in the hospital during the study period was 4118, thus giving a hospital-based incidence of neonatal sepsis of 7.04/1000 for in-born patients. The male:female ratio was 1.2:1. Overall Staphylococcus aureus was the commonest pathogen, accounting for 18 (29.5%) of the total isolates. Other pathogens were as follows; coagulase negative Saphylococcus albus 15 (24.6%), Klebsiella spp 10 (16.4%) and unclassified Coliforms 9 (14.8%). The predominant organisms in the first 48 hours were Gram negative bacilli; accounting for (70%) of the 10 isolates. Between 3 and 7 days of life the Gram positive cocci accounted for 12 (60%) of the 20 isolates while the Gram negative bacilli represented 40%. After 7 days, the predominant organism was Staphylococcus aureus (38.8%) while coagulase-negative Staphylococci were isolated in 7 of 31 isolates (22.6%). The sensitivity pattern showed that 94% of the organisms were sensitive to azythromicin, 77.8% to streptomycin, 73.3% to gentamicin and 69.2% to ampicillin-sulbactam. For the cephalosporins the isolates showed a sensitivity rate of 69% to ceftriaxone, 66.7% to ceftazidime and 58.3% to cefuroxime. As a group the Gram positive organisms had 100% sensitivity to Azythromcin, 85% to ampicillin-sulbactam, 63% to ceftazidime and 62.5% to gentamicin. In the Gram negative group, the best overall sensitivity was to ceftriaxone (86.4%). Gentamicin had 85.7% while sensitivity to ceftazidime was 60%. The distribution of the organisms causing early and late onset sepsis were different. For early onset sepsis, the Gram negative bacilli as a group were the commonest organisms while Staphylococcus aureus was the commonest cause of late onset sepsis. There was a lower incidence of sepsis compared to reports from other parts of the country. This, in addition to differences in antibiotic sensitivity pattern call for more multi-centre studies on predictors of neonatal sepsis. The antibiotic sensitivity profiles suggest that the initial empirical choice of ampicillin-sulbactam and gentamicin appears to be the most rational for our environment. PMID:12518907

  1. Ultrastructural Changes in Clinical and Microbiota Isolates of Klebsiella pneumoniae Carriers of Genes blaSHV, blaTEM, blaCTX-M, or blaKPC When Subject to β-Lactam Antibiotics

    PubMed Central

    Veras, Dyana Leal; de Souza Lopes, Ana Catarina; Vaz da Silva, Grasielle; Araújo Gonçalves, Gabriel Gazzoni; de Freitas, Catarina Fernandes; de Lima, Fernanda Cristina Gomes; Vieira Maciel, Maria Amélia; Feitosa, Ana Paula Sampaio; Alves, Luiz Carlos; Brayner, Fábio André

    2015-01-01

    The aim of this study was to characterize the ultrastructural effects caused by β-lactam antibiotics in Klebsiella pneumoniae isolates. Three K. pneumoniae clinical isolates were selected for the study with resistance profiles for third-generation cephalosporins, aztreonam, and/or imipenem and with different resistance genes for extended-spectrum β-lactamases (ESBL) or Klebsiella pneumoniae carbapenemase (KPC). Two K. pneumoniae isolates obtained from the microbiota, which were both resistant to amoxicillin and ampicillin, were also analyzed. In accordance with the susceptibility profile, the clinical isolates were subjected to subminimum inhibitory concentrations (sub-MICs) of cefotaxime, ceftazidime, aztreonam, and imipenem and the isolates from the microbiota to ampicillin and amoxicillin, for analysis by means of scanning and transmission electron microscopy. The K. pneumoniae isolates showed different morphological and ultrastructural changes after subjection to β-lactams tested at different concentrations, such as cell filamentation, loss of cytoplasmic material, and deformation of dividing septa. Our results demonstrate that K. pneumoniae isolates harboring different genes that encode for β-lactamases show cell alterations when subjected to different β-lactam antibiotics, thus suggesting that they possess residual activity in vitro, despite the phenotypic resistance presented in the isolates analyzed. PMID:26491715

  2. Impact of the Use of β-Lactam Antimicrobials on the Emergence of Escherichia coli Isolates Resistant to Cephalosporins under Standard Pig-Rearing Conditions

    PubMed Central

    Cameron-Veas, Karla; Solà-Ginés, Marc; Moreno, Miguel A.; Fraile, Lorenzo

    2014-01-01

    The aim of this study was to evaluate if the treatments with ceftiofur and amoxicillin are risk factors for the emergence of cephalosporin resistant (CR) E. coli in a pig farm during the rearing period. One hundred 7-day-old piglets were divided into two groups, a control (n = 50) group and a group parenterally treated with ceftiofur (n = 50). During the fattening period, both groups were subdivided in two. A second treatment with amoxicillin was administered in feed to two of the four groups, as follows: group 1 (untreated, n = 20), group 2 (treated with amoxicillin, n = 26), group 3 (treated with ceftiofur, n = 20), and group 4 (treated with ceftiofur and amoxicillin, n = 26). During treatment with ceftiofur, fecal samples were collected before treatment (day 0) and at days 2, 7, 14, 21, and 42 posttreatment, whereas with amoxicillin, the sampling was extended 73 days posttreatment. CR E. coli bacteria were selected on MacConkey agar with ceftriaxone (1 mg/liter). Pulsed-field gel electrophoresis (PFGE), MICs of 14 antimicrobials, the presence of cephalosporin resistance genes, and replicon typing of plasmids were analyzed. Both treatments generated an increase in the prevalence of CR E. coli, which was statistically significant in the treated groups. Resistance diminished after treatment. A total of 47 CR E. coli isolates were recovered during the study period; of these, 15 contained blaCTX-M-1, 10 contained blaCTX-M-14, 4 contained blaCTX-M-9, 2 contained blaCTX-M-15, and 5 contained blaSHV-12. The treatment with ceftiofur and amoxicillin was associated with the emergence of CR E. coli during the course of the treatment. However, by the time of finishing, CR E. coli bacteria were not recovered from the animals. PMID:25548055

  3. Determination of the second autoproteolytic cleavage site of cephalosporin C acylase and the effect of deleting its flanking residues in the ?-C-terminal region.

    PubMed

    Zhang, Jing; Yu, Huimin; Wang, Ying; Luo, Hui; Shen, Zhongyao

    2014-08-20

    Self-activation through two-step intra-molecular cleavages is of great importance for the synthesis of mature and functional cephalosporin acylase in the N-terminal nucleophile (Ntn) hydrolase superfamily. A synthetic gene for cephalosporin C acylase (sCPCAcy) from Pseudomonas sp. SE83 was overexpressed, and the self-activated sCPCAcy was produced in Escherichia coli JM109(DE3)/pET28-sCPCAcy. The first autoproteolytic cleavage site of Pre-sCPCAcy was determined to be G239-S240 according to the common features of Ntn hydrolases. The second cleavage site was identified as A232-S233 by C-terminus tandem MS/MS analysis of the purified ?-subunit, which released a 7-aa spacer peptide with the generation of the ? and ? subunits of the mature sCPCAcy. The effect of the cleavage-site-flanking residues in the ?-C-terminal region of sCPCAcy on its activation and characteristics was further evaluated. Residue G229 was found to be crucial for the first cleavage of Pre-sCPCAcy. Deletions in the ?-C-terminal region were performed, and 14 mutant proteins were constructed. The majority of the fragment-deleted mutant proteins completely lost their activity due to failure of the first autocleavage, but this loss was not observed in mutant proteins D2 (227-AM-228 deletion) and D4 (212-ADLA-215 deletion), which formally activated into mature sCPCAcy with high activity. The Kcat/Km values of mutant proteins D2 and D4 were 46% and 102% higher than that of the original control, respectively. PMID:24874096

  4. Antibiotic resistance is ancient.

    PubMed

    D'Costa, Vanessa M; King, Christine E; Kalan, Lindsay; Morar, Mariya; Sung, Wilson W L; Schwarz, Carsten; Froese, Duane; Zazula, Grant; Calmels, Fabrice; Debruyne, Regis; Golding, G Brian; Poinar, Hendrik N; Wright, Gerard D

    2011-09-22

    The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to ?-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use. PMID:21881561

  5. Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.

    PubMed

    Clendennen, T E; Echeverria, P; Saengeur, S; Kees, E S; Boslego, J W; Wignall, F S

    1992-08-01

    The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta-lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase-negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%. PMID:1416851

  6. Genetic Architecture of Intrinsic Antibiotic Susceptibility

    PubMed Central

    Tavazoie, Saeed

    2009-01-01

    Background Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. Methodology/Principal Findings To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance. Conclusions/Significance Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect. PMID:19462005

  7. Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae

    PubMed Central

    Peterson, S. W.; Martin, I.; Demczuk, W.; Bharat, A.; Hoang, L.; Wylie, J.; Allen, V.; Lefebvre, B.; Tyrrell, G.; Horsman, G.; Haldane, D.; Garceau, R.; Wong, T.

    2015-01-01

    The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ≥2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results. PMID:25878350

  8. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections.

    PubMed

    Krupp, Karl; Madhivanan, Purnima

    2015-01-01

    The emergence of multi-drug resistant sexually transmitted infections (STIs) is causing a treatment crisis across the globe. While cephalosporin-resistant gonorrhea is one of the most pressing issues, extensively antibiotic resistant Chlamydia trachomatis and Mycoplasma hominis are also becoming commonplace. Experts have suggested that the failure of current treatment regimens are "largely inevitable" and have called for entirely new classes of antimicrobial agents. With the exception of several new classes of drugs primarily targeting nosocomial infections, progress has been slow. While pharmaceutical companies continue to introduce new drugs, they are based on decade-old discoveries. While there is disagreement about what constitutes new classes of antibiotics, many experts suggest that the last truly new family of antimicrobials was discovered in 1987. This review summarizes the existing literature on antibiotic resistance in common bacterial and protozoal STIs. It also briefly discusses several of the most promising alternatives to current therapies, and further examines how advances in drug delivery, formulation, concentration, and timing are improving the efficacy of existing treatments. Finally, the paper discusses the current state of pharmaceutical development for multidrug-resistant STI. PMID:26392647

  9. Aetiology and antibiotic resistance issues regarding urological procedures.

    PubMed

    Concia, Ercole; Azzini, Anna Maria

    2014-10-01

    There are specific indications in urological procedures [transurethral resection of the prostate (TURP), transurethral resection of the bladder (TURB), endoscopic procedures, and all interventions classified as contaminated or dirty] requiring antibiotic prophylaxis. Most postoperative infections are caused by enterococci of the Gram-positive strains and Enterobacteriaceae of the Gram-negative ones. As reported by the European Center for Disease Prevention and Control (ECDC), there are increasing numbers of antibiotic-resistant pathogens. Most Enterococcus faecium strains are ampicillin-resistant and the Enterobacteriaceae have a high prevalence of extended-spectrum beta-lactamase (ESBL) producers, for which the cephalosporins and penicillins are not drugs of choice. In recent years, there are also increasing numbers of Gram-negative strains that are able to produce carbapenemases and for which the only therapeutic options are gentamicin, tigecycline and colistin. An alternative to these drugs, from a prophylactic point of view, is fosfomycin, an old antibiotic that maintains bactericidal activity against both enterococci and multidrug-resistant Enterobacteriaceae. Available in an oral formulation as trometamol salt, fosfomycin reaches high plasma and urine concentrations, and is therefore a possible alternative to other drugs both for therapy and urological prophylaxis. PMID:25245707

  10. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections

    PubMed Central

    Krupp, Karl; Madhivanan, Purnima

    2015-01-01

    The emergence of multi-drug resistant sexually transmitted infections (STIs) is causing a treatment crisis across the globe. While cephalosporin-resistant gonorrhea is one of the most pressing issues, extensively antibiotic resistant Chlamydia trachomatis and Mycoplasma hominis are also becoming commonplace. Experts have suggested that the failure of current treatment regimens are largely inevitable and have called for entirely new classes of antimicrobial agents. With the exception of several new classes of drugs primarily targeting nosocomial infections, progress has been slow. While pharmaceutical companies continue to introduce new drugs, they are based on decade-old discoveries. While there is disagreement about what constitutes new classes of antibiotics, many experts suggest that the last truly new family of antimicrobials was discovered in 1987. This review summarizes the existing literature on antibiotic resistance in common bacterial and protozoal STIs. It also briefly discusses several of the most promising alternatives to current therapies, and further examines how advances in drug delivery, formulation, concentration, and timing are improving the efficacy of existing treatments. Finally, the paper discusses the current state of pharmaceutical development for multidrug-resistant STI. PMID:26392647

  11. Management of meningitis due to antibiotic-resistant Acinetobacter species

    PubMed Central

    Kim, Baek-Nam; Peleg, Anton Y; Lodise, Thomas P; Lipman, Jeffrey; Li, Jian; Nation, Roger; Paterson, David L

    2009-01-01

    Acinetobacter meningitis is becoming an increasingly common clinical entity, especially in the postneurosurgical setting, with mortality from this infection exceeding 15%. Infectious Diseases Society of America guidelines for therapy of postneurosurgical meningitis recommend either ceftazidime or cefepime as empirical coverage against Gram-negative pathogens. However, assessment of the pharmacodynamics of these cephalosporins in cerebrospinal fluid suggests that recommended doses will achieve pharmacodynamic targets against fewer than 10% of contemporary acinetobacter isolates. Thus, these antibiotics are poor options for suspected acinetobacter meningitis. From in vitro and pharmacodynamic perspectives, intravenous meropenem plus intraventricular administration of an aminoglycoside may represent a superior, albeit imperfect, regimen for suspected acinetobacter meningitis. For cases of meningitis due to carbapenem-resistant acinetobacter, use of tigecycline is not recommended on pharmacodynamic grounds. The greatest clinical experience rests with use of polymyxins, although an intravenous polymyxin alone is inadvisable. Combination with an intraventricularly administered antibiotic plus removal of infected neurosurgical hardware appears the therapeutic strategy most likely to succeed in this situation. Unfortunately, limited development of new antibiotics plus the growing threat of multidrug-resistant acinetobacter is likely to increase the problems posed by acinetobacter meningitis in the future. PMID:19324297

  12. Evaluation of antibiotic prescription in the Lebanese community: a pilot study

    PubMed Central

    Saleh, Nadine; Awada, Sanaa; Awwad, Rana; Jibai, Sahar; Arfoul, Chadi; Zaiter, Liliana; Dib, Wissam; Salameh, Pascale

    2015-01-01

    Background Antibiotics are considered among the most commonly prescribed drug classes in developing countries. Inappropriate prescription of antibiotics is a major public health concern and is related to the development of antimicrobial resistance. Objective This study aimed at assessing the appropriateness of antibiotic prescription by non-infectious disease physicians in a community setting in Lebanon. Methods A pilot cross-sectional study was undertaken on community pharmacy patients presenting with antibiotic prescription. It was performed over a period of 4 months in different regions of Lebanon. Participants answered a questionnaire inquiring about socio-demographic characteristics, medical conditions, symptoms that required medical attention, the doctor's diagnosis, the prescribed antibiotic, and whether laboratory tests were ordered to identify the causative organism or not. Data were analyzed using SPSS 17. Results We studied 270 patients (49.3% males and 50.7% females). This study showed that the most-prescribed antibiotics were the cephalosporins (82%) and that almost half of the illnesses for which antibiotics were prescribed were respiratory tract infections (41%). The study also showed that the choice of the prescribed antibiotic was appropriate in 61.5% of the studied cases, while the prescribed dose and the duration of the treatment were inaccurate in 52 and 64% of the cases, respectively. In addition, fever seemed to be a factor that influenced the physician's prescriptions, since the choice of drug conformity to guidelines increased from 53.7% (1 day of fever) to 88.9% (1 week of fever), and the dose prescription compliance to guidelines was higher (55.9%) for patients suffering from fever compared to those with no fever (38.1%). Conclusion This study showed a high prevalence of inappropriate antibiotic prescriptions in Lebanon. Therefore, actions should be taken to optimize antibiotic prescription. PMID:26112266

  13. A Prospective Study of Single-Dose Antibiotic Prophylaxis in Live Donor Nephrectomy

    PubMed Central

    Jang, Ho Sung; Choi, Kyung Hwa; Yang, Seung Choul

    2011-01-01

    Purpose To perform a prospective analysis of the clinical outcomes of prophylactic antibiotic treatment before the standard surgical modality of living donor nephrectomy (LDN) without postoperative antibiotic treatment. Materials and Methods From November 2005 to June 2010, a total of 470 patients underwent LDN at our medical institution, and 280 of these patients were injected with 1 g cephalosporin 30 minutes before the operation. The group receiving prophylactic antibiotics was compared with a control group composed of 190 patients who received injections of 2 g cephalosporin per day for 5 days after the operation. The presence of fever, incidence of blood transfusion, and period of drainage use were compared between the two groups. Results There were no significant differences in gender, age, body mass index, incidence of blood transfusion after the operation, fever over 38℃ 3 days after the operation, or period of drain insertion between the single-dose group and the control group. The follow-up was conducted for 1 month after the operation, and 1 case of surgical site infection (SSI) was observed in each group (p=0.783). Conclusions Of 280 patients in the single-dose group, 1 contracted SSI. In comparison with the control group, which was dosed with prophylactic antibiotics for 5 days after the operation, the single-dose group did not have a significantly different occurrence of SSI. We found that the incidence rate of SSI did not increase, even though prophylactic antibiotics were not used after standard and conventional open surgeries, such as video-assisted minilaparotomy surgery. PMID:21379428

  14. Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16 years: non-linear time series analysis

    PubMed Central

    Lawes, Timothy; López-Lozano, José-María; Nebot, César; Macartney, Gillian; Subbarao-Sharma, Rashmi; Dare, Ceri R J; Edwards, Giles F S; Gould, Ian M

    2015-01-01

    Objectives To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Design Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Setting Regional hospital and primary care in a Scottish Health Board. Participants General adult (N=1 051 993) or intensive care (18 235) admissions and primary care registrations (460 000 inhabitants) between January 1997 and December 2012. Interventions Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and ‘4Cs’ (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Outcome measures Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10 000 inhabitant-days). Results 67% of all clinical MRSA isolates (10 707/15 947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of ‘4Cs’ and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R2=0.63–0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4 days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135–141, and 48–81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. Conclusions Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts. PMID:25814495

  15. Developing New Antibiotics with Combinatorial Biosynthesis

    NASA Astrophysics Data System (ADS)

    Pohl, Nicola L.

    2000-11-01

    Polyketide synthases (PKSs), a class of enzymes found in soil bacteria that produce antibiotics such as erythromycin, string together acetate units using basic organic reactions. The manipulation of the sequence of these reactions at the genetic level has resulted in an alteration of the corresponding chemical structure of the antibiotic produced by the bacteria. This process, called combinatorial biosynthesis, allows the generation of many presently unknown complex structures that can be tested for antibacterial activity, thereby contributing to the race against antibiotic-resistant infectious bacteria.

  16. A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?

    PubMed Central

    Baietto, Lorena; Corcione, Silvia; Pacini, Giovanni; Di Perri, Giovanni; D’Avolio#†, Antonio; Giuseppe De Rosa†, Francesco

    2014-01-01

    Drug bioavailability may vary greatly amongst individuals, affecting both efficacy and toxicity: in humans, genetic variations account for a relevant proportion of such variability. In the last decade the use of pharmacogenetics in clinical practice, as a tool to individualize treatment, has shown a different degree of diffusion in various clinical fields. In the field of infectious diseases, several studies identified a great number of associations between host genetic polymor-phisms and responses to antiretroviral therapy. For example, in patients treated with abacavir the screening for HLA-B*5701 before starting treatment is routine clinical practice and standard of care for all patients; efavirenz plasma levels are influenced by single nucleotide polymorphism (SNP) CYP2B6-516G> T (rs3745274). Regarding antibiotics, many studies investigated drug transporters involved in antibiotic bioavailability, especially for fluoroquinolones, cephalosporins, and antituberculars. To date, few data are available about pharmacogenetics of recently developed antibiotics such as tigecycline, daptomycin or linezolid. Considering the effect of SNPs in gene coding for proteins involved in antibiotics bioavailability, few data have been published. Increasing knowledge in the field of antibiotic pharmacogenetics could be useful to explain the high drug inter-patients variability and to individualize therapy. In this paper we reported an overview of pharmacokinetics, pharmacodynamics, and pharmacogenetics of antibiotics to underline the importance of an integrated approach in choosing the right dosage in clinical practice. PMID:24909419

  17. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    PubMed

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone (?antibiotic resistance was to the macrolides [azithromycin (56.4?%) and erythromycin (51.6?%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome. PMID:26408040

  18. On the use of antibiotics to reduce rhizoplane microbial populations in root physiology and ecology investigations

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ferro, A.; Ritchie, K.; Bugbee, B. G.

    1995-01-01

    No straightforward method exists for separating the proportion of ion exchange and respiration due to rhizoplane microbial organisms from that of root ion exchange and respiration. We examined several antibiotics that might be used for the temporary elimination of rhizoplane bacteria from hydroponically grown wheat roots (Triticum aestivum cv. Veery 10). Each antibiotic was tested for herbicidal activity and plate counts were used to enumerate bacteria and evaluate antibiotic kinetics. Only lactam antibiotics (penicillins and cephalosporins) did not reduce wheat growth rates. Aminoglycosides, the pyrimidine trimethoprim, colistin and rifampicin reduced growth rates substantially. Antibiotics acted slowly, with maximum reductions in rhizoplane bacteria occurring after more than 48 h of exposure. Combinations of nonphytotoxic antibiotics reduced platable rhizoplane bacteria by as much as 98%; however, this was generally a reduction from about 10(9) to 10(6) colony forming units per gram of dry root mass, so that many viable bacteria remained on root surfaces. We present evidence which suggests that insufficient bacterial biomass exists on root surfaces of nonstressed plants grown under well-aerated conditions to quantitatively interfere with root nitrogen absorption measurements.

  19. Antibiotic resistance of Gram-negative benthic bacteria isolated from the sediments of Kardzhali Dam (Bulgaria)

    PubMed Central

    Iliev, Ivan; Marhova, Mariana; Gochev, Velizar; Tsankova, Marinela; Trifonova, Sonya

    2015-01-01

    The aim of the present study was to carry out a preliminary assessment for the occurrence of bacterial strains resistant to frequently used antibiotics in the sediments beneath the sturgeon cage farm in Kardzhali Dam (Bulgaria). Samples were taken from the top 2 cm of sediments under a fish farm and from a control station in the aquatory of the reservoir in the period July–October 2011. Surveillance of bacterial susceptibility to 16 antimicrobial agents was performed for 160 Gram-negative strains (Pseudomonas mandelii – 100 strains; Hafnia alvei – 30 strains; and Raoultella ornithinolytica – 30 strains). No significant differences in the resistance to the tested antibiotics were observed between the strains isolated from the two stations (analysis of variance, P > 0.05). Widespread resistance to penicillins and certain cephalosporin antibiotics was observed in both stations. None of the studied strains showed resistance to the aminoglycoside antibiotics gentamicin and amikacin, or to ciprofloxacin. Minimal Inhibitory Concentrations (MIC) were determined for five of the tested antimicrobial agents by the microdilution antibiotic sensitivity assay. The data indicate that amikacin, tetracycline and ciprofloxacin effectively suppress the growth of the tested micro-organisms. The isolates from genus Pseudomonas showed the highest MIC and were characterized by the highest percentage of antibiotic resistance. PMID:26019641

  20. Frontline antibiotic therapy.

    PubMed

    MacGowan, Alasdair; Albur, Maha

    2013-06-01

    The need to use front-line antibiotics wisely has never been greater. Antibiotic resistance and multi-drug resistant infection, driven by antibiotic use, remain major public health and professional concerns. To overcome these infection problems, use of older antibiotics active against multi drug-resistant pathogens is increasing - for example, colistin, fosfomycin, pivmecillinam, pristinamycin, temocillin and oral tetracyclines. The number of new antibacterials reaching clinical practice has reduced significantly in the last 20 years, most being focused on therapy of Gram-positive infection - eg linezolid, daptomycin, telavancin and ceftaroline. Recent guidance on antibiotic stewardship in NHS trusts in England is likely to provide a backdrop to antibiotic use in hospitals in the next 5 years. PMID:23760700

  1. Biotic acts of antibiotics

    PubMed Central

    Aminov, Rustam I.

    2013-01-01

    Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and β-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

  2. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments

    PubMed Central

    Chait, Remy; Palmer, Adam C.; Yelin, Idan; Kishony, Roy

    2016-01-01

    Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance. PMID:26787239

  3. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments.

    PubMed

    Chait, Remy; Palmer, Adam C; Yelin, Idan; Kishony, Roy

    2016-01-01

    Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance. PMID:26787239

  4. Prescription antibiotics for outpatients in Bangladesh: a cross-sectional health survey conducted in three cities

    PubMed Central

    2014-01-01

    Background Antibiotics prescribing by physicians have gained due importance across the globe, mainly because of an increase in antibiotic usage, prevalence of infections and drug resistances. The present study is aimed to evaluate the physicians prescribing pattern of antibiotics, their usages by outpatients and disease conditions for which the antibiotics are prescribed in three cities of Bangladesh. Methods This cross sectional health survey was carried out with a self designed standard questionnaire by manual data collection over a three months period (20.03.2013 to 20.06.2013) at three adjacent cities Jessore Sadar, Monirampur and Keshabpur upazila respectively. The data were collected from the patients prescription and by directly interviewing the patients who were prescribed at least one antibiotic during the study period. WHO Anatomical Therapeutic Chemical (ATC) classifications for antibiotics was used and descriptive statistics were applied to the collected data and analyzed using Microsoft Excel software. Modified Wald method was applied to calculate 95% CI. Results A total of 900 prescriptions were analyzed during the study period. It was found that the prescriber prescribed antibiotics to the patients who were suffering mainly from cold and fever, infections, diarrhea and gonorrhea. The highest prescribed antibiotic groups were cephalosporins (31.78%), macrolides (27.33%), quinolones (16.33%), penicillins (7.11%), and metronidazoles (6.78%) respectively. Two or more antibiotics were prescribed in 25.44% of prescriptions. A total of 66.89% prescriptions had complete information on dosage form, 57% had complete direction for antibiotics use and 64.22% patients completed full course of antibiotics. Although 83% prescriptions have no clinical test for using antibiotics, even though the percentages of patients disease recovery were 61.78% and incompliance were 38.22%. Conclusion From this research, it is observed that physicians prescribed antibiotics rationally in some cases but needs to ensure in all cases of prescription. Because irrational use leads to the spread of bacterial resistance to antibiotics and related health problems, our findings have important implications for public education and the enforcement of regulations regarding the prescription of antibiotics in Bangladesh. PMID:24755269

  5. ?-Lactams and Florfenicol Antibiotics Remain Bioactive in Soils while Ciprofloxacin, Neomycin, and Tetracycline Are Neutralized?

    PubMed Central

    Subbiah, Murugan; Mitchell, Shannon M.; Ullman, Jeffrey L.; Call, Douglas R.

    2011-01-01

    It is generally assumed that antibiotic residues in soils select for antibiotic-resistant bacteria. This assumption was tested by separately adding 10 different antibiotics (?200 ppm) to three soil-water slurries (silt-loam, sand-loam, and sand; 20% soil [wt/vol]) and incubating mixtures for 24 h at room temperature. The antibiotic activity of the resultant supernatant was assessed by culturing a sensitive Escherichia coli strain in the filter-sterilized supernatant augmented with Luria-Bertani broth. We found striking differences in the abilities of supernatants to suppress growth of the indicator E. coli. Ampicillin, cephalothin, cefoxitin, ceftiofur, and florfenicol supernatants completely inhibited growth while bacterial growth was uninhibited in the presence of neomycin, tetracycline, and ciprofloxacin supernatants. High-performance liquid chromatography (HPLC) analysis demonstrated that cefoxitin and florfenicol were almost completely retained in the supernatants, whereas tetracycline and ciprofloxacin were mostly removed. Antibiotic dissipation in soil, presumably dominated by adsorption mechanisms, was sufficient to neutralize 200 ppm of tetracycline; this concentration is considerably higher than reported contamination levels. Soil pellets from the tetracycline slurries were resuspended in a minimal volume of medium to maximize the interaction between bacteria and soil particles, but sensitive bacteria were still unaffected by tetracycline (P = 0.6). Thus, residual antibiotics in soil do not necessarily exert a selective pressure, and the degree to which the pharmaceutical remains bioactive depends on the antibiotic. Efforts to control antibiotic contamination would be better directed toward compounds that retain biological activity in soils (e.g., cephalosporins and florfenicol) because these are the antibiotics that could exert a selective pressure in the environment. PMID:21856822

  6. Ultrasound-assisted matrix solid phase dispersive extraction for the simultaneous analysis of ?-lactams (four penicillins and eight cephalosporins) in milk by high performance liquid chromatography with photodiode array detection.

    PubMed

    Karageorgou, Eftichia G; Samanidou, Victoria F; Papadoyannis, Ioannis N

    2012-10-01

    The application of ultrasound-assisted matrix solid phase dispersive extraction for the confirmatory analysis of 12 ?-lactam antibiotics in milk by high performance liquid chromatography with photodiode array detection has been proposed herein. Four penicillins (cloxacillin, dicloxacillin, oxacillin, and amoxicillin) and eight cephalosporins (cefaclor, cefadroxil, ceftiofur, cefuroxime, cefoperazone, cefazolin, cephalexin, and cefotaxime) are effectively extracted using a mixed sorbent of Quick Easy Cheap Effective Rugged Safe technique and OASIS HLB providing a matrix free from any endogenous interference. Examined analytes were well resolved on an Inertsil ODS-3 analytical column with a mobile phase of CH(3)COONH(4) (0.05 M) and acetonitrile delivered under a gradient program. 1,7-Dimethyl-xanthine was used as internal standard. The method was validated meeting the European Legislation determining linearity, selectivity, stability, decision limit, detection capability, accuracy, precision, and ruggedness according to the Youden approach. Recoveries of all antibiotics rated from 85.0 to 115.7%, while RSD values were <12.7%. Finally, the method was successfully applied to milk samples purchased from local market. PMID:22941669

  7. Efficient biocatalyst for large-scale synthesis of cephalosporins, obtained by combining immobilization and site-directed mutagenesis of penicillin acylase.

    PubMed

    Cecchini, Davide A; Pavesi, Roberto; Sanna, Sara; Daly, Simona; Xaiz, Roberto; Pregnolato, Massimo; Terreni, Marco

    2012-09-01

    We describe the rational design of a new efficient biocatalyst and the development of a sustainable green process for the synthesis of cephalosporins bearing a NH? group on the acyl side chain. The new biocatalyst was developed starting from the WT penicillin acylase (PA) from Escherichia coli by combining enzyme mutagenesis, in position ?146 and ?24 (?F24A/?F146Y), and immobilization on an appropriate modified industrial support, glyoxyl Eupergit C250L. The obtained derivative was used in the kinetically controlled synthesis of cephalexin, cefprozil and cefaclor and compared to the WT-PA and an already described mutant, PA-?F24A, with improved properties. The new biocatalyst posses a very high ratio between the rates of the synthesis and two undesired hydrolyses (acylating ester and the amidic product). In particular, a very low amidase activity was observed with PA-?F24A/?F146Y and, consequently, the hydrolysis of the produced antibiotic was avoided during the process. Taking advantage of this property, higher conversions in the synthesis of cephalexin (99% versus 76%), cefaclor (99% versus 65%) and cefprozil (99% versus 60%) were obtained compared to the WT enzyme. Furthermore, the new mutant also show a higher synthetic activity compared to PA-?F24A immobilized on the same support, allowing the maximum yields to be achieved in very short reaction times. The production of cephalexin with the immobilized ?F24A/?F146Y acylase has been developed on a pre-industrial scale (30 l). After 20 cycles, the average yield was 93%. The biocatalyst showed good stability properties and no significant decrease in performance. PMID:22228258

  8. Persistence of antibiotic resistance in bacterial populations.

    PubMed

    Andersson, Dan I; Hughes, Diarmaid

    2011-09-01

    Unfortunately for mankind, it is very likely that the antibiotic resistance problem we have generated during the last 60 years due to the extensive use and misuse of antibiotics is here to stay for the foreseeable future. This view is based on theoretical arguments, mathematical modeling, experiments and clinical interventions, suggesting that even if we could reduce antibiotic use, resistant clones would remain persistent and only slowly (if at all) be outcompeted by their susceptible relatives. In this review, we discuss the multitude of mechanisms and processes that are involved in causing the persistence of chromosomal and plasmid-borne resistance determinants and how we might use them to our advantage to increase the likelihood of reversing the problem. Of particular interest is the recent demonstration that a very low antibiotic concentration can be enriching for resistant bacteria and the implication that antibiotic release into the environment could contribute to the selection for resistance. Several mechanisms are contributing to the stability of antibiotic resistance in bacterial populations and even if antibiotic use is reduced it is likely that most resistance mechanisms will persist for considerable times. PMID:21707669

  9. [Grouping of the genes of biosynthesis and resistance to beta-lactam antibiotics in cephamycin-C producing actinomycetes].

    PubMed

    Liras, P; Coque, J J; García-Calzada, J; Pérez Llarena, F J; Cardoza, R E

    1994-01-01

    Three genes related to beta-lactam resistance have been found in the cluster of genes for cephamycin C biosynthesis in Nocardia lactamdurans. The cmcT gene encodes a hydrophobic protein located in the cytoplasmic membrane. The sequence of CMCT has a 21-31% identity in amino acids to proteins involved in antibiotic export from other antibiotic producing microorganisms. The pbp gene encodes a penicillin binding protein. Nocardia lactamdurans is rather sensitive to penicillins, but no to cephalosporins or cephamycin C. A third gene, bla, encodes a type A beta-lactamase. Both the beta-lactamase and the PBP protein, might form a system for the sensing and hydrolysis of penicillin intermediates which are released into the medium during the lysis of antibiotic producing cells. PMID:7946127

  10. Sorption Mechanisms of Antibiotic Cephapirin onto Quartz and Feldspar by Raman Spectroscopy

    SciTech Connect

    Peterson, Jonathan; Wang, Wei; Gu, Baohua

    2009-01-01

    Raman spectroscopy was used to investigate the sorption mechanisms of cephapirin (CHP), a veterinary antibiotic, onto quartz (SiO2) and feldspar (KAlSi3O8) at different pH values. Depending on the charge and surface properties of the mineral, different reaction mechanisms including electrostatic attraction, monodentate and bidentate complexation were found to be responsible for CHP sorption. The zwitterion (CHPo) adsorbs to a quartz(+) surface by electrostatic attraction of the carboxylate anion group ( COO-) at a low pH, but adsorbs to a quartz(-) surface through electrostatic attraction of the pyridinium cation and possibly COO- bridge complexes at relatively higher pH conditions. CHP- bonds to a quartz(-) surface by bidentate complexation between one oxygen of COO- and oxygen from the carbonyl (C=O) of the acetoxymethyl group. On a feldspar surface of mixed charge, CHPo forms monodentate complexes between C=O as well as COO- bridging complexes or electrostatically attached to localized edge (hydr)oxy-Al surfaces. CHP- adsorbs to feldspar(-) through monodentate C=O complexation, and similar mechanisms may operate for the sorption of other cephalosporins. This research demonstrates, for the first time, that Raman spectroscopic techniques can be effective for evaluating the sorption processes and mechanisms of cephalosporin antibiotics even at relatively low sorbed concentrations (97-120 μmol/kg).

  11. Analysis of 12 beta-lactam antibiotics in human plasma by HPLC with ultraviolet detection.

    PubMed

    McWhinney, Brett C; Wallis, Steven C; Hillister, Tara; Roberts, Jason A; Lipman, Jeffrey; Ungerer, Jacobus P J

    2010-07-15

    A simple and economical high performance liquid chromatography method was developed and validated for routine analysis of 12 Penicillin, Cephalosporin and Carbapenem antibiotics in 200 microL of human plasma. Antibiotics determined were Ceftazidime, Meropenem, Ceftriaxone, Ampicillin, Cefazolin, Ertapenem, Cephalothin, Benzylpenicillin, Flucloxacillin, Dicloxacillin, Piperacillin and Ticarcillin. There was a common sample preparation approach involving precipitation of proteins with acetonitrile and removal of lipid-soluble components by a chloroform wash. Separations were performed on a Waters X-bridge C18 column with, depending on analytes, one of three acetonitrile-phosphate buffer mobile phases. Detection was by UV at 210, 260 and 304 nm. Validation has demonstrated the method to be linear, accurate and precise. The method has been used in a pathology laboratory for therapeutic drug monitoring (TDM) of beta-lactams in critically ill patients. PMID:20561826

  12. In vitro activity of cefditoren versus other antibiotics against S. pneumoniae clinical strains isolated in Italy.

    PubMed

    Tempera, G; Furneri, P M; Ferranti, C; Genovese, C; Ripa, S; Ungheri, S; Nicoletti, G

    2010-01-01

    Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 micrograms/ml obtained could be particularly significant in therms of therapeutic predictivity. PMID:20943054

  13. Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs

    SciTech Connect

    Wang, Xiaojun; Minasov, George; Shoichet, Brian K.

    2010-03-08

    Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the {beta}-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182 {yields} Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.

  14. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  15. Replacement for antibiotics: Lysozyme

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics have been fed at subtherapeutic levels to swine as growth promoters for more than 60 years, and the majority of swine produced in the U.S. receive antibiotics in their feed at some point in their production cycle. These compounds benefit the producers by minimizing production losses by ...

  16. The future of antibiotics.

    PubMed

    Spellberg, Brad

    2014-01-01

    Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on 'push' incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

  17. The future of antibiotics

    PubMed Central

    2014-01-01

    Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

  18. [beta-lactam-antibiotics in the treatment of community-acquired respiratory tract infections with penicillin-resistant pneumococci].

    PubMed

    Brauers, J; Ewig, S; Kresken, M

    2002-10-01

    Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections. During the last decades in many countries an increase in the spread of antibiotic resistant strains (e. g. against beta-lactams, macrolides, tetracyclin) was observed. Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes. In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L). Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively. According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft fr Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections. As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains. beta-Lactam-antibiotics highly differ in their in-vitro-activity against S. pneumoniae and their pharmacokinetic properties. In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i. e. not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC). In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment. PMID:12375222

  19. [Determination of 9 cephalosporin drug residues in beef by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Bai, Guotao; Chu, Xiaogang; Pan, Guoqing; Li, Xiuqin; Yong, Wei

    2009-07-01

    A confirmative method to determine 9 cephalosporin residues in beef by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed. The sample was homogenized and extracted with acetonitrile and water for 1 min at 14,000 r/min, centrifuged at 10,000 r/min and 4 degrees C for 10 min. A total of 2 mL saturated sodium chloride solution was added to avoid foaming during the acetonitrile evaporation, the acetonitrile was evaporated below 37 degrees C using a rotary evaporator, and then cleaned up on an Oasis HLB (500 mg, 6 mL) SPE column by washing with 5 mL water and eluting with acetonitrile-water (7:3, v/v). The eluate was blown to dryness under a stream of nitrogen and adjusted to 3.0 mL with water. The separation was carried out on an ACQUITY UPLC BEH C18 column within 5 min, analyzed by UPLC-MS/MS system with external standard method. The limits of quantification (LOQs) of cefuroxime, ceftiofur and cefalonium were 10, 0.5 and 0.5 microg/kg, respectively; the LOQs of other cephalosporins were 1.0 microg/kg. The recoveries of cephalosporins ranged from 74.2% to 119% and the relative standard deviations (RSDs) ranged from 2.9% to 15% for the spiked beef sample. The method is quick, easy, very sensitive and suitable for the determination of cephalosporin residues in beef. PMID:19938495

  20. BEL-2, an extended-spectrum beta-lactamase with increased activity toward expanded-spectrum cephalosporins in Pseudomonas aeruginosa.

    PubMed

    Poirel, Laurent; Docquier, Jean-Denis; De Luca, Filomena; Verlinde, Annemie; Ide, Louis; Rossolini, Gian Maria; Nordmann, Patrice

    2010-01-01

    A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate. PMID:19884378

  1. BEL-2, an Extended-Spectrum ?-Lactamase with Increased Activity toward Expanded-Spectrum Cephalosporins in Pseudomonas aeruginosa?

    PubMed Central

    Poirel, Laurent; Docquier, Jean-Denis; De Luca, Filomena; Verlinde, Annemie; Ide, Louis; Rossolini, Gian Maria; Nordmann, Patrice

    2010-01-01

    A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum -lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The blaBEL-2 gene was identified from a P. aeruginosa isolate clonally related to another blaBEL-1-positive isolate. PMID:19884378

  2. Incidence of Extended-Spectrum-?-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates That Test Susceptible to Cephalosporins and Aztreonam by the Revised CLSI Breakpoints

    PubMed Central

    Condon, Susan; Schwartz, Rebecca M.; Ginocchio, Christine C.

    2014-01-01

    The incidence of aztreonam and cephalosporin susceptibility, determined using the revised CLSI breakpoints, for extended-spectrum-?-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates was evaluated. Our analysis showed that results for aztreonam and/or ?1 cephalosporin were reported as susceptible or intermediate for 89.2% of ESBL-producing E coli isolates (569/638 isolates) and 67.7% of ESBL-producing K. pneumoniae isolates (155/229 isolates). PMID:24789185

  3. Prediction of hydrolysis pathways and kinetics for antibiotics under environmental pH conditions: a quantum chemical study on cephradine.

    PubMed

    Zhang, Haiqin; Xie, Hongbin; Chen, Jingwen; Zhang, Shushen

    2015-02-01

    Understanding hydrolysis pathways and kinetics of many antibiotics that have multiple hydrolyzable functional groups is important for their fate assessment. However, experimental determination of hydrolysis encounters difficulties due to time and cost restraint. We employed the density functional theory and transition state theory to predict the hydrolysis pathways and kinetics of cephradine, a model of cephalosporin with two hydrolyzable groups, two ionization states, two isomers and two nucleophilic attack directions. Results showed that the hydrolysis of cephradine at pH = 8.0 proceeds via opening of the ?-lactam ring followed by intramolecular amidation. The predicted rate constants at different pH conditions are of the same order of magnitude as the experimental values, and the predicted products are confirmed by experiment. This study identified a catalytic role of the carboxyl group in the hydrolysis, and implies that the carboxyl group also plays a catalytic role in the hydrolysis of other cephalosporin and penicillin antibiotics. This is a first attempt to quantum chemically predict hydrolysis of an antibiotic with complex pathways, and indicates that to predict hydrolysis products under the environmental pH conditions, the variation of the rate constants for different pathways with pH should be evaluated. PMID:25590945

  4. Two-step immobilized enzyme conversion of cephalosporin C to 7-aminocephalosporanic acid.

    PubMed

    Conlon, H D; Baqai, J; Baker, K; Shen, Y Q; Wong, B L; Noiles, R; Rausch, C W

    1995-06-20

    The first large-scale production of 7-aminocephalosporanic acid (7ACA) from cephalosporin C (CPC) using a wholly enzymatic synthesis method is reported here. We produced 7ACA from CPC in as high a molar yield as 85% using the immobilized enzymes D-amino acid oxidase (D-AOD) and glutaryl-7-ACA acylase (GL-acylase). In the first reactor, CPC is converted to keto-adipyl-7-aminocephalosporanic acid (keto-7ACA) using an immobilized D-AOD isolated from a yeast, Trigonopsis variabilis. The keto-7ACA is then spontaneously converted to glutaryl-7-aminocephalosporanic acid (GL-7ACA) via a chemical reaction with hydrogen peroxide. The hydrogen peroxide is also a product of the D-AOD reaction. Near quantitative conversion of the keto-7ACA to GL-7ACA was observed. The second reactor converts GL-7ACA to 7ACA using an immobilized GL-acylase, which was isolated from a recombinant Escherichia coli. The final 7ACA crystalline product is a high quality product. The reactions are conducted under very mild aqueous conditions: pH 8.0 and 20 degrees to 25 degrees C. The production of desacetyl side products is minimal. This process is currently being implemented on an industrial scale to produce 7ACA. PMID:18623345

  5. Immobilization of a cephalosporin acetylesterase by containment within an ultrafiltration device.

    PubMed

    Abbott, B J; Cerimele, B; Fukuda, D S

    1976-08-01

    A cephalosporin acetylesterase produced by Bacillus subtilis catalyzes the deacetylation of 7-aminocephalosporanic acid (7-ACA). Previous reports from our laboratory described the kinetic constants that characterize the reaction: Km = 2.8 X 10(-3)M, Kia acetate = 5 X 10(-2)M, and Kid deacetyl-7-ACA = 3.6 X 10(-2)M. These constants were used to predict the time course of the reaction using the following equation for dual competitive product inhibition. (see article) where St =mg/ml 7-ACA, At =mg/ml acetate, Dt =mg/ml deacetyl-7-ACA. The predicted time course closely matched the time course measured experimentally. The equation also was solved without the inhibition terms and the solution indicated that product inhibition caused about a 30% increase in the time required for complete (greater than 97%) hydrolysis of a 24 mg/ml 7-ACA solution. The esterase was immobilized by containment within an ultrafiltration device. With this technique the enzyme was reused 20 times over an 11 day span to deacetylate 7-ACA solutions containing 4 to 24 mg/ml 7-ACA. The specific activity after the 20th use was the same as the activity prior to the first use, indicating little enzyme inactiviation occurred. PMID:953166

  6. Prevalence of Ambler class A ?-lactamases and ampC expression in cephalosporin-resistant isolates of Acinetobacter baumannii.

    PubMed

    Rezaee, Mohammad Ahangarzadeh; Pajand, Omid; Nahaei, Mohammad Reza; Mahdian, Reza; Aghazadeh, Mohammad; Ghojazadeh, Morteza; Hojabri, Zoya

    2013-07-01

    We examined the prevalence of various cephalosporins' resistance mechanisms in Acinetobacter baumannii clinical isolates. Phenotypic and molecular detection of Ambler classes A, B and D ?-lactamases was performed on 75 isolates. Clonal relatedness was defined using Repetitive Extragenic Palindromic PCR. PCR mapping was used to examine the linkage of insertion sequences and the ampC gene, and ampC expression was analyzed by TaqMan reverse transcriptase-PCR. Twenty-six (37%) isolates carried at least one of the blaPER-1 or blaTEM-1. Sixty-nine (98.5%) out of 70 cephalosporin-resistant isolates had insertions upstream of the ampC gene, of which 48 (69%) and 6 (8%) were identified as ISAba1and ISAba125, respectively. Higher level of expression was obtained in resistant isolates lacking ISAba1/ampC combination in comparison with that in positive ones. The ability to up-regulate the expression of ampC gene in association with different insertion elements has become an important factor in A. baumannii resistance to cephalosporins. PMID:23726148

  7. Antibiotic susceptibility of bacteria isolated from respiratory tract of pigs in Poland between 2004 and 2008.

    PubMed

    Markowska-Daniel, I; Urbaniak, K; Stepniewska, K; Pejsak, Z

    2010-01-01

    Antibiotic susceptibility of bacteria isolated from nasal swabs and lungs of pigs, to 16 commonly used antibiotics, was determined by disc diffusion test. beta-lactams showed the best activity against Streptococcus suis (S. suis) (> 99% of susceptible strains). The lowest sensitivity of S. suis was evidenced to: tylosin, tetracycline and neomycin (50%, 40% and 25%, respectively). Isolates of Escherichia coli (E. coli) demonstrated the highest susceptibility to cephalosporin (85% strains), gentamicin and norfloxacin (over 74%). The lowest susceptibility of E. coli was demonstrated to tiamulin and penicillin (11.3% and 1.9%, respectively). Over 80% of Actinobacillus pleuropneumoniae (App) strains were susceptible to all antibiotics tested. The highest resistance of App, but demonstrated by below 20% of tested isolates only, was evidenced to neomycin and LxS. Isolates of Pasteurella multocida (Pm), Haemophilus parasuis (Hps) and Arcanobacterium pyogenes (A. pyogenes) were highly susceptible to the most antibiotics included in the analysis. The comparison of the in vitro susceptibility of pathogens to the chemotherapeutics used on Polish farms for the therapy of bacterial infection of pigs within the last five years and the last 10 years, showed an increasing percent of E. coli and S. suis strains resistant to commonly used antibiotics. It is also shown that Pm, Hps, App and A. pyogenes isolates were continuously susceptible to the most chemotherapeutics applied. PMID:21077428

  8. Effects of six antibiotics and their binary mixtures on growth of Pseudokirchneriella subcapitata.

    PubMed

    Magdaleno, A; Saenz, M E; Jurez, A B; Moretton, J

    2015-03-01

    The effect of ampicillin (AMP), amoxicillin (AMX), cephalotin (CEP), ciprofloxacin (CPF), gentamycin (GEN), and vancomycin (VAN) have been examined individually and as binary mixtures, on a non-target aquatic organism, the green alga Pseudokichneriella subcapitata. The ?-lactam antibiotics AMP and AMX were not toxic to the alga at concentrations up to 2000 mgl(-1) (less than 10% of algal growth inhibition), whereas the fluoroquinolone CPF, and the aminoglycoside GEN were the most toxic antibiotics, with an EC50=11.3 0.7 mgl(-1) and 19.2 0.5 mgl(-1), respectively. The cephalosporin CEP and the glycopeptide VAN were less toxic than the last two mentioned, showing an EC50>600 mgl(-1) and 724 20 mgl(-1), respectively. The toxicological interactions of binary mixtures were predicted by the two classical models of additivity: concentration addition (CA) and independent action (IA), and compared to the experimentally determined toxicities over a range of concentrations between 1 and 50 mgl(-1). In all cases a clear synergistic effect was observed, showing that single compound toxicity data are not adequate for the prediction of aquatic toxicities of antibiotic mixtures. Risk assessment was performed by calculating the ratio between predicted environmental concentrations (PEC) and the predicted no effect concentration (PNEC). All the antibiotics tested, excepting GEN, have a potential ecological risk, taking into account the PEC of hospital effluents from Buenos Aires, Argentina. These risks increase when antibiotics are present in binary mixtures. PMID:25483375

  9. Biosensors, antibiotics and food.

    PubMed

    Virolainen, Nina; Karp, Matti

    2014-01-01

    Antibiotics are medicine's leading asset for fighting microbial infection, which is one of the leading causes of death worldwide. However, the misuse of antibiotics has led to the rapid spread of antibiotic resistance among bacteria and the development of multiple resistant pathogens. Therefore, antibiotics are rapidly losing their antimicrobial value. The use of antibiotics in food production animals is strictly controlled by the European Union (EU). Veterinary use is regulated to prevent the spread of resistance. EU legislation establishes maximum residue limits for veterinary medicinal products in foodstuffs of animal origin and enforces the establishment and execution of national monitoring plans. Among samples selected for monitoring, suspected noncompliant samples are screened and then subjected to confirmatory analysis to establish the identity and concentration of the contaminant. Screening methods for antibiotic residues are typically based on microbiological growth inhibition, whereas physico-chemical methods are used for confirmatory analysis. This chapter discusses biosensors, especially whole-cell based biosensors, as emerging screening methods for antibiotic residues. Whole-cell biosensors can offer highly sensitive and specific detection of residues. Applications demonstrating quantitative analysis and specific analyte identification further improve their potential as screening methods. PMID:25216955

  10. Antibiotics and Resistance: Glossary

    MedlinePLUS

    ... the normal function of microscopic organisms, including bacteria, fungi, yeast, viruses and protozoa. Antibiotics, which affect only ... Physical elements that form one's surroundings. Fungus (Plural: fungi) A multicellular organism with cell walls and nuclei, ...

  11. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePLUS

    ... Antibiotic Type of antimicrobial agent made from a mold or bacterium that kills or slows the growth ... slow the growth of microbes including bacteria , viruses , fungi and parasites . Antimicrobial resistance Antimicrobial resistance is the ...

  12. From antiseptics to antibiotics and back?

    PubMed Central

    Assadian, Ojan

    2007-01-01

    There is no straight line to trace the trajectory of antiseptics; rather, this has been manifested more as a fluctuating line, a backwards and forwards movement, seen in the wake of major discoveries but of colossal mistakes too. While today no one would allow their prophylactic policies to be guided by miasma or contagia, there continues to be some uncertainly about how to manage anti-infectives effectively even today. When in 1941 the first human being was successfully treated with penicillin, interest in antiseptics gradually waned. From that time onwards, everything was treated with antibiotics, unleashing a race for the discovery of novel antibiotics, as witnessed decades earlier in the case of antiseptics. The significance of antiseptics declined to such an extent that among physicians they were associated merely with cleaning agents or sanitary disinfection. Today, at the beginning of the 21st century we know that the euphoria generated by antibiotics was just another station along the pathway of discoveries. Bacterial infections and new, hitherto unknown infectious diseases continue to play a major role. Several viral infections continue to be refractory to successful treatment and bacterial antibiotic resistance has become a problem worldwide. The most effective countermeasures no longer entail only the development of new antibiotics but above all responsible management of antibiotics and strict observance of infection control measures in the hospital setting. Set against that background, interest in antiseptics has been rekindled. In that spirit we can look eagerly forward over the coming years to further developments in antisepsis. PMID:20200687

  13. [Antibiotic therapy in psittacines].

    PubMed

    Krautwald, M E

    1989-01-01

    The use of different antibiotics in psittacines is described. Among other aspects especially the anatomy of the bird and its consequence for the application of medicaments is taken into account. The use of antibiotics in psittacines often turns out to be difficult because of missing data about their pharmacokinetics, dosage, period of application and their compatibility. In order to deal with the increasing number of pet-birds in the veterinary practice, further examinations have to be conducted. PMID:2655172

  14. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jrgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed the golden age of antibiotics. Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases. PMID:24326504

  15. Phenotypic Resistance to Antibiotics

    PubMed Central

    Corona, Fernando; Martinez, Jose L.

    2013-01-01

    The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  16. HR 756, a highly active cephalosporin: comparison with cefazolin and carbenicillin.

    PubMed

    Wise, R; Rollason, T; Logan, M; Andrews, J M; Bedford, K A

    1978-12-01

    HR 756, a new parenteral cephalosporin, was compared with cefazolin and carbenicillin for activity against a total of 264 strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus spp. (indole positive), Enterobacter spp., Salmonella typhi, Serratia marcescens, Providencia stuartii, and Staphylococcus aureus. In every comparison, except that with the last organism, HR 756 was clearly more active than cefazolin and carbenicillin. All three compounds had similar activity against penicillin-susceptible staphylococci; against penicillin-resistant strains, HR 756 and cefazolin were equally active and superior to carbenicillin. HR 756 was compared with penicillin for activity against strains of Streptococcus pyogenes, Lancefield group D streptococci, and Neisseria gonorrhoeae; with ampicillin against Haemophilus influenzae; and with cefoxitin against Bacteriodes fragilis. HR 756 was clearly more active than the respective reference compounds in all of these comparisons, except those involving the streptococci. HR 756 and penicillin were essentially equally active against S. pyogenes; against Lancefield group D, penicillin was 32 times as active as HR 756. HR 756 not only compared favorably with the reference compounds with respect to relative activity, but also effected growth inhibition of essentially all test organisms (P. aeruginosa and group D streptococci excepted) at remarkably low concentrations ranging from 0.015 to 2.0 mug/ml. A series of seven transfers of selected strains of E. coli, Klebsiella spp., S. aureus, and P. aeruginosa through medium containing HR 756 led to emergence of strains with significant levels of resistance to the agent. Resistance to HR 756 was retained for at least seven transfers through plain medium. PMID:253572

  17. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

  18. Eight More Ways To Deal with Antibiotic Resistance

    PubMed Central

    Shlaes, David M.

    2014-01-01

    The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics. PMID:24867992

  19. Eight more ways to deal with antibiotic resistance.

    PubMed

    Metz, Matthew; Shlaes, David M

    2014-08-01

    The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics. PMID:24867992

  20. Antibiotic therapy for ocular infection.

    PubMed Central

    Snyder, R W; Glasser, D B

    1994-01-01

    Infections of the eye can rapidly damage important functional structures and lead to permanent vision loss or blindness. Broad-spectrum antibiotics should be administered to the appropriate site of infection as soon as a diagnosis is made. Topical drops are preferred for corneal and conjunctival infections. Intravitreal antibiotics, and possibly subconjunctival and parenteral antibiotics, are preferred for endophthalmitis. Parenteral antibiotics are recommended for infection in deep adnexal structures. We review specific aspects of antibiotic therapy for ocular and periocular infection. PMID:7856158

  1. Reversing resistance: The next generation antibacterials

    PubMed Central

    Shah, Neel Jayesh

    2015-01-01

    Irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to “preantibiotic era.” The threat is serious with the “Enterococcus, Staphylococcous, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter” organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum β-lactamases, carbapenamases and metallo-β-lactamases. Facing us is a situation where soon multidrug resistance would have spread across the globe with no antibiotics to withstand it. The infectious disease society of America and Food and Drug Administration have taken initiatives like the 10 × ‘20 where they plan to develop 10 new antibiotics by the year 2020. Existing classes of antibiotics against resistant bacteria include the carbapenems, oxazolidinones, glycopeptides, monobactams, streptogramins and daptomycin. Newer drugs in existing classes of antibiotics such as cephalosporins, aminoglycosides, tetracyclines, glycopeptides and β-lactamase inhibitors continue to get synthesized. The situation demands newer targets against bacterial machinery. Some of them include the peptidoglycantransferase, outer membrane protein of Pseudomonas, tRNA synthase, fatty acid synthase and mycobacterial ATP synthase. To curb the irrational and excessive usage of presently available antibiotics should be a priority if they are still to be kept in usage for the future. PMID:26069360

  2. Reversing resistance: The next generation antibacterials.

    PubMed

    Shah, Neel Jayesh

    2015-01-01

    Irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to "preantibiotic era." The threat is serious with the "Enterococcus, Staphylococcous, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter" organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum ?-lactamases, carbapenamases and metallo-?-lactamases. Facing us is a situation where soon multidrug resistance would have spread across the globe with no antibiotics to withstand it. The infectious disease society of America and Food and Drug Administration have taken initiatives like the 10 '20 where they plan to develop 10 new antibiotics by the year 2020. Existing classes of antibiotics against resistant bacteria include the carbapenems, oxazolidinones, glycopeptides, monobactams, streptogramins and daptomycin. Newer drugs in existing classes of antibiotics such as cephalosporins, aminoglycosides, tetracyclines, glycopeptides and ?-lactamase inhibitors continue to get synthesized. The situation demands newer targets against bacterial machinery. Some of them include the peptidoglycantransferase, outer membrane protein of Pseudomonas, tRNA synthase, fatty acid synthase and mycobacterial ATP synthase. To curb the irrational and excessive usage of presently available antibiotics should be a priority if they are still to be kept in usage for the future. PMID:26069360

  3. On the specificity of antibiotics targeting the large ribosomal subunit.

    PubMed

    Wilson, Daniel N

    2011-12-01

    The peptidyltransferase center of the large ribosomal subunit is responsible for catalyzing peptide bonds. This active site is the target of a variety of diverse antibiotics, many of which are used clinically. The past decade has seen a plethora of structures of antibiotics in complex with the large ribosomal subunit, providing unprecedented insight into the mechanism of action of these inhibitors. Ten distinct antibiotics (chloramphenicol, clindamycin, linezolid, tiamulin, sparsomycin, and five macrolides) have been crystallized in complex with four distinct ribosomal species, three bacterial, and one archaeal. This review aims to compare these structures in order to provide insight into the conserved and species-specific modes of interaction for particular members of each class of antibiotics. Coupled with the wealth of biochemical data, a picture is emerging defining the specific functional states of the ribosome that antibiotics preferentially target. Such mechanistic insight into antibiotic inhibition will be important for the development of the next generation of antimicrobial agents. PMID:22191523

  4. Outpatient Antibiotic Use and the Incidence of Acute Appendicitis in Finland: A Nationwide Study from 1990–2008

    PubMed Central

    Miettinen, Pekka; Huovinen, Pentti; Herzig, Karl H.; Alajääski, Jennyl; Salminen, Paulina; Paajanen, Hannu

    2013-01-01

    Abstract Background The incidence of acute appendicitis (AA) has decreased in Finland. We hypothesized that changing trends in outpatient antibiotic use might explain at least part of this declining incidence of AA. Methods The number of all patients with AA in Finland was extracted from the national data base from 1990 to 2008. For comparison, the incidence of acute diverticulitis of the colon (AD) was also recorded. All outpatient prescriptions of antibiotics belonging to the major groups of these drugs were also recorded. We used unit root and co-integration analyses for statistical analysis of the data in the study. Results The incidence of AA in Finland declined from 14.5 to 9.8 per 10,000 inhabitants (32%) and the incidence of AD increased by 47% between 1993 and 2007. The total outpatient use of antibiotics did not increase during this same period, but the use of antibiotics effective widely against colonic pathogens (macrolides, fluoroquinolones, and cephalosporins) increased significantly. No correlation was found between the incidence of AA, that of AD, and the use of different groups of antibiotics. Conclusions Our nationwide registry study indicated that changes in outpatient antibiotic use do not explain the decreasing trend in AA in Finland. Other factors, such as improved diagnosis of AA, may have some role in the decreasing incidence of AA. PMID:23859685

  5. Antibiotic Prescriptions in Critically-Ill Patients: A Latin American Experience

    PubMed Central

    Curcio, D

    2013-01-01

    Background: It is widely acknowledged that the presence of infection is an important outcome determinant for intensive care unit (ICU) patients. In fact, antibiotics are one of the most common therapies administered in the ICU settings. Aim: To evaluate the current usage of antibiotics in Latin American ICUs. Subjects and Methods: A one-day p-oint prevalence study to investigate the patterns of antibiotic was undertaken in 72 Latin American (LA) ICUs. Data was analyzed using the Statistix 8 statistical software, version 2.0 (USA). Results were expressed as proportions. When applicable, two tailed hypothesis testing for difference in proportions was used (Proportion Test); a P value of <0.05 was considered significant. Results: Of 704 patients admitted, 359 received antibiotic treatment on the day of the study (51%), of which 167/359 cases (46.5%) were due to hospital-acquired infections. The most frequent infection reorted was nosocomial pneumonia (74/359, 21%). Only in 264/359 patients (73.5%), cultures before starting antibiotic treatment were performed. Thirty-eight percent of the isolated microorganisms were Enterobacteriaceae extended-spectrum β-lactamase-producing, 11% methicillin-resistant Staphylococcus aureus and 10% carbapenems-resistant non-fermentative Gram-negatives. The antibiotics most frequently prescribed were carbapenems (125/359, 35%), alone or in combination with vancomycin or other antibiotic. There were no significant differences in the “restricted” antibiotic prescription (carbapenems, vancomycin, piperacillin–tazobactam, broad-spectrum cephalosporins, fluoroquinolones, tigecycline and linezolid) between patients with APACHE II score at the beginning of the antibiotic treatment <15 [83/114 (72.5%)] and ≥15 [179/245 (73%)] (P = 0.96). Only 29% of the antibiotic treatments were cultured directed (104/359). Conclusion: Carbapenems (alone or in combination) were the most frequently prescribed antibiotics in LA ICUs. However, the problem of carbapenem resistance in LA requires that physicians improve the use of this class of antibiotics. Our findings show that our web-based method for collection of one-day point prevalence was implemented successfully. However, based on the limitations of the model used, the results of this study must be taken with caution. PMID:23919194

  6. Ecological antibiotic policy.

    PubMed

    Hiby, N

    2000-09-01

    Development of resistance to antibiotics is a major problem worldwide. The normal oropharyngeal flora, the intestinal flora and the skin flora play important roles in this development. Within a few days after the onset of antibiotic therapy, resistant Escherichia coli, Haemophilus influenzae and Staphylococcus epidermidis can be detected in the normal flora of volunteers or patients. Horizontal spread of the resistance genes to other species, e.g. Salmonella spp., Staphylococcus aureus and Streptococcus pneumoniae, occurs by conjugation or transformation. An ecologically sound antibiotic policy favours the use of antibiotics with little or no impact on the normal flora. Prodrug antibiotics which are not active against the bacteria in the mouth and the intestine (before absorption) and which are not excreted to a significant degree via the intestine, saliva or skin are therefore preferred. Prodrugs such as pivampicillin, bacampicillin, pivmecillinam and cefuroxime axetil are favourable from an ecological point of view. Experience from Scandinavia supports this, since resistance to mecillinam after 20 years of use is low (about 5%) and stable. PMID:11051626

  7. Ecological antibiotic policy.

    PubMed

    Hiby

    2000-08-01

    Development of resistance to antibiotics is a major problem worldwide. The normal oropharyngeal flora, the intestinal flora and the skin flora play important roles in this development. Within a few days after the onset of antibiotic therapy, resistant Escherichia coli, Haemophilus influenzae and Staphylococcus epidermidis can be detected in the normal flora of volunteers or patients. Horizontal spread of the resistance genes to other species, e.g. SALMONELLA: spp., Staphylococcus aureus and Streptococcus pneumoniae, occurs by conjugation or transformation. An ecologically sound antibiotic policy favours the use of antibiotics with little or no impact on the normal flora. Prodrug antibiotics which are not active against the bacteria in the mouth and the intestine (before absorption) and which are not excreted to a significant degree via the intestine, saliva or skin are therefore preferred. Prodrugs such as pivampicillin, bacampicillin, pivmecillinam and cefuroxime axetil are favourable from an ecological point of view. Experience from Scandinavia supports this, since resistance to mecillinam after 20 years of use is low (about 5%) and stable. PMID:10969054

  8. An amperometric affinity penicillin-binding protein magnetosensor for the detection of ?-lactam antibiotics in milk.

    PubMed

    Gamella, M; Campuzano, S; Conzuelo, F; Esteban-Torres, M; de las Rivas, B; Reviejo, A J; Muoz, R; Pingarrn, J M

    2013-04-01

    The preparation, characterization and performance evaluation of an amperometric affinity disposable magnetosensor, based on the use of a recombinant penicillin-binding protein (PBP) and screen-printed carbon electrodes (SPCEs), for the specific detection and quantification of ?-lactam antibiotic residues in milk are reported. The PBP was immobilized onto His-Tag-Isolation-modified magnetic beads (His-Tag-Isolation-MBs), and a direct competitive assay using a tracer with horseradish peroxidase (HRP) for the enzymatic labeling was performed. The amperometric response obtained at -0.20 V vs. the Ag pseudo-reference electrode of the SPCE after the addition of H2O2 in the presence of hydroquinone (HQ) was used as the transduction signal. The developed methodology showed very low detection limits (in the low ppb level) for the 6 antibiotics tested in untreated milk samples, and a good selectivity against other antibiotic residues frequently detected in milk and dairy products. Due to the bioreceptor employed, this methodology was able to detect only the active form of ?-lactam antibiotics with high affinities for both penicillins and cephalosporins. Moreover, the analysis took only 30 min. PMID:23420036

  9. The multifaceted roles of antibiotics and antibiotic resistance in nature

    PubMed Central

    Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

    2013-01-01

    Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics in nature. PMID:23487476

  10. Use of charge-transfer complexation in the spectrophotometric analysis of certain cephalosporins.

    PubMed

    Saleh, G A; Askal, H F; Radwan, M F; Omar, M A

    2001-07-01

    Three simple, rapid and sensitive spectrophotometric procedures were developed for the analysis of cephapirin sodium (1), cefazoline sodium (2), cephalexin monohydrate (3), cefadroxil monohydrate (4), cefotaxime sodium (5), cefoperazone sodium (6) and ceftazidime pentahydrate (7) in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of these drugs as n-electron donors with the sigma-acceptor iodine, and the pi-acceptors: 2,3-dichloro-5,6-dicyano-p-benzo-quinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ). Depending on the solvent polarity, different coloured charge-transfer complexes and radicals were developed. Different variables and parameters affecting the reactions were studied and optimized. The obtained charge-transfer complexes were measured at 364 nm for iodine (in 1,2-dichloroethane), 460 nm for DDQ (in methanol) and 843 nm for TCNQ (in acetonitrile). Ultraviolet-visible, infrared and (1)H-nuclear magnetic resonance techniques were used to study the formed complexes. Due to the rapid development of colours at ambient temperature, the obtained results were used on thin-layer chromatograms for the detection of the investigated drugs. Beer's plots were obeyed in a general concentration range of 6-50, 40-300 and 4-24 mug ml(-1) with iodine, DDQ and TCNQ, respectively, with correlation coefficients not less than 0.9989. The proposed procedures could be applied successfully to the determination of the investigated drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 96.47 (+/-1.14) to 98.72 (+/-1.02) in the iodine method, 96.35 (+/-1.62) to 98.51 (+/-1.30) in the DDQ method, and 95.98 (+/-0.78) to 98.40 (+/-0.87) in the TCNQ method. The association constants and standard free energy changes using Benesi-Hildebrand plots were studied. The binding of cephalosporins to proteins in relation to their molar absorptivities was studied. PMID:18968341

  11. Molecular Characteristics of Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae from Humans in the Community

    PubMed Central

    van Hoek, Angela H. A. M.; Schouls, Leo; van Santen, Marga G.; Florijn, Alice; de Greeff, Sabine C.; van Duijkeren, Engeline

    2015-01-01

    Objective To investigate the molecular characteristics of extended-spectrum cephalosporin (ESC)-resistant Enterobacteriaceae collected during a cross-sectional study examining the prevalence and risk factors for faecal carriage of extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae in humans living in areas with high or low broiler density. Methods ESC-resistant Enterobacteriaceae were identified by combination disc-diffusion test. ESBL/AmpC/carbapenemase genes were analysed using PCR and sequencing. For E. coli, phylogenetic groups and MLST were determined. Plasmids were characterized by transformation and PCR-based replicon typing. Subtyping of plasmids was done by plasmid multilocus sequence typing. Results 175 ESC-resistant Enterobacteriaceae were cultured from 165/1,033 individuals. The isolates were Escherichia coli(n=65), Citrobacter freundii (n=52), Enterobacter cloacae (n=38), Morganella morganii (n=5), Enterobacter aerogenes (n=4), Klebsiella pneumoniae (n=3), Hafnia alvei (n=2), Shigella spp. (n=2), Citrobacter amalonaticus (n=1), Escherichia hermannii (n=1), Kluyvera cryocrescens (n=1), and Pantoea agglomerans (n=1). The following ESBL genes were recovered in 55 isolates originating from 49 of 1,033 (4.7 %) persons: blaCTX-M-1 (n=17), blaCTX-M-15 (n=16), blaCTX-M-14 (n=9), blaCTX-M-2 (n=3), blaCTX-M-3 (n=2), blaCTX-M-24 (n=2), blaCTX-M-27 (n=1), blaCTX-M-32 (n=1), blaSHV-12 (n=2), blaSHV-65 (n=1) and blaTEM-52 (n=1). Plasmidic AmpC (pAmpC) genes were discovered in 6 out of 1,033 (0.6 %) persons. One person carried two different E. coli isolates, one with blaCTX-M-1 and the other with blaCMY-2 and therefore the prevalence of persons carrying Enterobacteriaceae harboring ESBL and/or pAmpC genes was 5.2 %. In eight E. coli isolates the AmpC phenotype was caused by mutations in the AmpC promoter region. No carbapenemase genes were identified. A large variety of E. coli genotypes was found, ST131 and ST10 being most common. Conclusions ESBL/pAmpC genes resembled those from patients in Dutch hospitals, indicating that healthy humans form a reservoir for transmission of these determinants to vulnerable people. The role of poultry in the transmission to humans in the community remains to be elucidated. PMID:26029910

  12. Tensions in antibiotic prescribing.

    PubMed

    Metlay, Joshua P

    2002-05-01

    Since 1999, the Agency for Healthcare Research and Quality has funded seven centers across the country to provide practical guidance to physicians and other health care professionals about the drugs they prescribe. These Centers for Education and Research on Therapeutics (CERTs) develop, translate and disseminate objective information on drugs to improve practice. The University of Pennsylvania's CERTs focuses on developing evidence for optimal treatment strategies for infectious diseases, and promoting the judicious use of antibiotics to combat the problem of antibiotic resistance. This Issue Brief explores one of the fundamental challenges physicians face in optimizing antibiotic use: the potential conflict between what is best for an individual patient, and what is best for society as a whole. PMID:12528744

  13. Antibiotic activity in space.

    PubMed

    Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R

    1986-01-01

    Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon. PMID:3569006

  14. Antibiotic Precautions in Athletes

    PubMed Central

    Fayock, Kristopher; Voltz, Matthew; Sandella, Bradley; Close, Jeremy; Lunser, Matthew; Okon, Joshua

    2014-01-01

    Context: Antibiotics are the mainstay of treatment for bacterial infections in patients of all ages. Athletes who maximally train are at risk for illness and various infections. Routinely used antibiotics have been linked to tendon injuries, cardiac arrhythmias, diarrhea, photosensitivity, cartilage issues, and decreased performance. Evidence Acquisition: Relevant articles published from 1989 to 2012 obtained through searching MEDLINE and OVID. Also, the Food and Drug Administration website was utilized. Study Design: Clinical review. Level of Evidence: Level 3. Results: The team physician should consider alternative medications in place of the drug of choice when adverse drug effects are a concern for an athletes health or performance. If alternative medications cannot be selected, secondary preventative measures, including sunscreen or probiotics, may be needed. Conclusion: Physicians choose medications based on a variety of factors to help ensure infection resolution while limiting potential side effects. Extra precautions are indicated when treating athletes with certain antibiotics. PMID:24982704

  15. Antibiotic prophylaxis in otolaryngologic surgery

    PubMed Central

    Ottoline, Ana Carolina Xavier; Tomita, Shiro; Marques, Marise da Penha Costa; Felix, Felippe; Ferraiolo, Priscila Novaes; Laurindo, Roberta Silveira Santos

    2013-01-01

    Summary Aim: Antibiotic prophylaxis aims to prevent infection of surgical sites before contamination or infection occurs. Prolonged antibiotic prophylaxis does not enhance the prevention of surgical infection and is associated with higher rates of antibiotic-resistant microorganisms. This review of the literature concerning antibiotic prophylaxis, with an emphasis on otolaryngologic surgery, aims to develop a guide for the use of antibiotic prophylaxis in otolaryngologic surgery in order to reduce the numbers of complications stemming from the indiscriminate use of antibiotics. PMID:25991999

  16. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  17. Antibiotics in Animal Products

    NASA Astrophysics Data System (ADS)

    Falco, Amlcar C.

    The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

  18. Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (19982012): emergence of multidrug-resistant clones less susceptible to cephalosporins

    PubMed Central

    2014-01-01

    Background The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. Methods We compared the characteristics of Ng detected during 19982001 (n?=?26) to those detected during 20092012 (n?=?34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. Results The following susceptibility results were obtained (period: % of non-S, MIC90 in mg/L): penicillin (19982001: 42.3%, 3; 20092012: 85.3%, 16), cefixime (19982001: 0%, ?0.016; 20092012: 8.8%, 0.125), ceftriaxone (19982001: 0%, 0.004; 20092012: 0%, 0.047), ciprofloxacin (19982001: 7.7%, 0.006; 20092012: 73.5%, ?32), azithromycin (19982001: 11.5%, 0.25; 20092012: 23.6%, 0.38), tetracycline (19982001: 65.4%, 12; 20092012: 88.2%, 24), spectinomycin (19982001: 0%, 12; 20092012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 19982001 to 70.6% in 20092012. International STs and genogroups (G) emerged during 20092012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). Conclusions The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close. PMID:24568221

  19. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy.

    PubMed

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B H

    2016-04-01

    Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa. PMID:27019964

  20. Immobilization of microbial cells in crosslinked, prepolymerized, linear polyacrylamide gels: antibiotic production by immobilized Streptomyces clavuligerus cells

    SciTech Connect

    Freeman, A.; Aharonowitz, Y.

    1981-12-01

    A mild method for the immobilization of whole microbial cells has been developed. Cells were suspended in a solution of preformed, linear, water-soluble polyacrylamide chains, partially substituted with acylhydrazide groups. The prepolymerized backbone polymer was crosslinked, in the presence of viable cells, by stoichiometric amounts of dialdehydes such as glyoxal, glutardialdehyde, and periodate-oxidized polyvinyl alcohol. The crosslinking reaction, carried out in cold, neutral physiological conditions resulted in cells entrapped in gels with physical properties similar to those of the common polyacrylamide gels. However, cell damage generally caused by the acrylamide monomer was avoided. Resting Streptomyces clavuligerus cells, possessing a high capacity for antibiotic production, were entrapped according to this procedure. These immobilized cells produced cephalosporins continuously for 96 hours with yields similar to those of free resting cells. The same cells, when immobilized by direct polymerization of acrylamide monomers, yielded significantly lower amounts of antibiotics. (Refs. 19).

  1. Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride

    SciTech Connect

    Harvey, R.A.; Alcid, D.V.; Greco, R.S.

    1982-09-01

    Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

  2. [Recombinant cephalosporin-acid synthesase: optimisation of expression in E.coli cells, immobilisation and application for biocatalytic cefazolin synthesis].

    PubMed

    Eldarov, M A; Sklyarenko, A V; Dumina, M V; Medvedeva, N V; Jgoun, A A; Satarova, J E; Sidorenko, A I; Emperian, A S; Yarotsky, S V

    2015-01-01

    Cephalosporin acid synthetase (CASA) is responsible for specific to synthesis of cephalosporin-acids, its expression in Escherichia coli cells is accompanied by accumulation of unprocessed insoluble precursor. In order to optimize conditions of recombinant CASA production we have studied the effects of several parameters of strain cultivation, including growth media composition, temperature, and inoculation dose. Also plasmids for production of CASA variants with the signal sequence of Erwinia carotovora L-asparaginase (ansCASA) and "leaderless" CASA were created in search of more efficient expression constructs. Removal of the N-terminal secretion signal sequence reduced the production of functionally active CASA more than 10-fold and inhibited strain growth. Insertion of the L-asparaginase signal sequence increased the specific enzyme activity in the resultant recombinant strain. The ansCASA producing strain was used to develop the method of immobilization of the recombinant enzyme on an epoxy-activated macroporous acrylic support. The resultant biocatalyst performed effective synthesis of cefazolin from 3-[(5-methyl-1,3,4-thiadiazol-2-il)-thiomethyl]-7- aminocephalosporanic acid (MMTD-7-ACA) and methyl ester of 1(H)-tetrazolilacetic acid (?ETzAA), under mild conditions a transformation level of MMTD-7-ACA to cefazolin of 95% is reached. PMID:26539875

  3. Oriented immobilization and characterization of a poly-lysine-tagged cephalosporin C acylase on glyoxyl agarose support.

    PubMed

    Luo, Hui; Zhao, Huan; Chang, Yanhong; Wang, Qixin; Yu, Huimin; Shen, Zhongyao

    2015-02-01

    Cephalosporin C acylase (CCA), an important industrial enzyme for the production of 7-aminocephalosporanic acid, has very limited and scattered surface lysine residues. A mutant of cephalosporin C acylase (mCCA) has been designed to fuse a poly-lysine tag to the C-terminal of the ?-subunit, which is far away from the active site. The free mCCA showed a near equal specific activity with the wild-type CCA, while a much higher activity recovery was obtained for the mCCA than its wild-type counterpart after immobilization on glyoxyl agarose support (73.3 versus 53.3 %). The mCCA's oriented immobilization enables it to obtain a higher substrate affinity and even a higher thermal stability than the wild-type enzyme. The improvement of stability might be attributed to the multipoint covalent attachment by the oriented enzyme immobilization via the adhered poly-lysine tag, which prevents the dissociation of the ?-subunit of CCA from the support. PMID:25448633

  4. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and in some cases suggest that sensitivity to existing antibiotics may be restored, in otherwise drug resistant organisms. PMID:25458541

  5. Antibiotics before surgery.

    PubMed

    Kaatz, B

    1996-01-01

    The antimicrobial era (along with greater surgical skill and precision) has brought us relative safety for procedures that previously were fraught with danger. Civil War amputation surgeries, for example, had an extraordinarily high incidence of infections and mortality. Staying aware of and avoiding the small, but real, risks associated with surgical antibiotic prophylaxis will help sustain the advances we enjoy today. PMID:8650524

  6. Antibiotic therapy of cholera*

    PubMed Central

    Lindenbaum, John; Greenough, William B.; Islam, M. R.

    1967-01-01

    Recent clinical trials having established the value of tetracycline as an adjunct to fluid and electrolyte replacement in cholera treatment, a controlled trial of antibiotic therapy was conducted in Dacca on 318 adults hospitalized for cholera. The effects of 4 antibiotics orally administered in varying dosage schedules were studied. Cholera therapy with tetracycline or chloramphenicol caused a highly significant reduction in the duration of diarrhoea and of positive culture, in stool volume, and in intravenous fluid requirement as compared with the results in controls who received intravenous fluid therapy only. Streptomycin was also effective, but to a lesser degree; paromomycin was of little value. The severity of dehydration on admission was significantly related to subsequent duration of diarrhoea regardless of whether antibiotics were given. Increasing age was associated with more prolonged purging in patients receiving antibiotics. Increasing the dose of tetracycline to 2 to 3 times that usually administered, or prolonging treatment from 2 to 4 days, did not enhance the therapeutic results. The effect of tetracycline was apparent within a few hours of administration. Bacteriological relapses were seen after discontinuation of therapy in all treatment groups, but were not due to the development of resistant bacteria. PMID:4865453

  7. Mission Critical: Preventing Antibiotic Resistance

    MedlinePLUS

    ... can we do to prevent antibiotic resistance in healthcare settings? Patients, healthcare providers, healthcare facility administrators, and ... hygiene and getting recommended vaccines. View Larger Graphic Healthcare providers can: Prescribe antibiotics correctly – get cultures, ...

  8. Antibiotic-Resistant Gonorrhea (ARG)

    MedlinePLUS

    ... please visit this page: About CDC.gov . Gonorrhea Antibiotic Resistance Basic Information Laboratory Information Resources & References Facts & Brochures ... Page Surveillance Trends and Treatment Challenges Laboratory Issues Antibiotic resistance (AR) is the ability of bacteria to resist ...

  9. Bacterial cheating limits antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

    2012-02-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

  10. De novo Comparative Transcriptome Analysis of Acremonium chrysogenum: High-Yield and Wild-Type Strains of Cephalosporin C Producer

    PubMed Central

    Liu, Yan; Xie, Liping; Gong, Guihua; Zhang, Wei; Zhu, Baoquan; Hu, Youjia

    2014-01-01

    β-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium chrysogenum is an important industrial fungus for the production of CPC, one of the major precursors of β-lactam antibiotics. Although its fermentation yield has been bred significantly over the past decades, little is known regarding molecular changes between the industrial strain and the wild type strain. This limits the possibility to improve CPC production further by molecular breeding. Comparative transcriptome is a powerful tool to understand the molecular mechanisms of CPC industrial high yield producer compared to wild type. A total of 57 million clean sequencing reads with an average length of 100 bp were generated from Illumina sequencing platform. 22,878 sequences were assembled. Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences were assigned to 121 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we compared the transcriptome differences between a high-yield and a wild-type strain during fermentation. A total of 4329 unigenes with significantly different transcription level were identified, among which 1737 were up-regulated and 2592 were down-regulated. 24 pathways were subsequently determined which involve glycerolipid metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the transcription levels of 18 identified genes, including 11 up-regulated genes and 7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR). The results of RT-qPCR were consistent with the Illumina sequencing. In this study, the Illumina sequencing provides the most comprehensive sequences for gene expression profile of Acremonium chrysogenum and allows de novo transcriptome assembly while lacking genome information. Comparative analysis of RNA-seq data reveals the complexity of the transcriptome in the fermentation of different yield strains. This is an important public information platform which could be used to accelerate the research to improve CPC production in Acremonium chrysogenum. PMID:25118715

  11. Mass flow of antibiotics in a wastewater treatment plant focusing on removal variations due to operational parameters.

    PubMed

    Marx, Conrad; Günther, Norbert; Schubert, Sara; Oertel, Reinhard; Ahnert, Markus; Krebs, Peter; Kuehn, Volker

    2015-12-15

    Wastewater treatment plants (WWTPs) are not designed to purposefully eliminate antibiotics and therefore many previous investigations have been carried out to assess their fate in biological wastewater treatment processes. In order to consolidate previous findings regarding influencing factors like the solid and hydraulic retention time an intensive monitoring was carried out in a municipal WWTP in Germany. Over a period of 12months daily samples were taken from the in- and effluent as well as diverse sludge streams. The 14 selected antibiotics and one metabolite cover the following classes: cephalosporins, diaminopyrimidines, fluoroquinolones, lincosamide, macrolides, penicillins, sulfonamides and tetracyclines. Out of the 15 investigated substances, the removal of only clindamycin and ciprofloxacin show significant correlations to SRT, temperature, HRT and nitrogen removal. The dependency of clindamycin's removal could be related to the significant negative removal (i.e. production) of clindamycin in the treatment process and was corrected using the human metabolite clindamycin-sulfoxide. The average elimination was adjusted from -225% to 3% which suggests that clindamycin can be considered as an inert substance during the wastewater treatment process. Based on the presented data, the mass flow analysis revealed that macrolides, clindamycin/clindamycin-sulfoxide and trimethoprim were mainly released with the effluent, while penicillins, cephalosporins as well as sulfamethoxazole were partly degraded in the studied WWTP. Furthermore, levofloxacin and ciprofloxacin are the only antibiotics under investigation with a significant mass fraction bound to primary, excess and digested sludge. Nevertheless, the sludge concentrations are highly inconsistent which leads to questionable results. It remains unclear whether the inconsistencies are due to insufficiencies in sampling and/or analytical determination or if the fluctuations can be considered reasonable for digesters. Hence, future investigations have to address antibiotic's temporal dynamics during the sludge treatment to decide whether or not the widely reported standard deviations of sludge concentrations reflect realistic fluctuations. PMID:26340581

  12. Minocycline: far beyond an antibiotic.

    PubMed

    Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

    2013-05-01

    Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

  13. Minocycline: far beyond an antibiotic

    PubMed Central

    Garrido-Mesa, N; Zarzuelo, A; Glvez, J

    2013-01-01

    Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

  14. The role and types of antibiotics, depending on the injuries of soldiers of IX and X Polish military contingent in Afghanistan.

    PubMed

    Ziemba, Radosław

    2012-01-01

    The frequency of external wounds sustained by soldiers on the modern battlefield is not declining. In particular, this concerns participants in humanitarian and stabilization missions in the third world countries, almost daily attacked with improvised booby-traps and firing missiles or multi-caliber weapons. The wound infection rate is high, which requires often the empirical use of antibiotics, both in local dressings, as well as the overall dose. The knowledge of the probable causative agent of a wound infection, its theoretical susceptibility to the antibiotic and spectrum antibiotics that are currently available, is a factor which is conditional in the success of treatment. In order to investigate, how the supply of PKW Afghanistan in antibiotics and chemotherapeutic drugs is presented and whether this supply range is suitable for medical problems, we analyzed the consumption of these drugs. Data for the years: 2010-2011 were available. The supply structure was dominated by antibiotics penicillin, cephalosporin, amino glycoside and macrolide. It was stated that each year the supply and consumption of antibiotics increased by 127.9%, with a stable number of serving people and a stable number of sustained injuries. Compared to 2010, in 2011 there were purchases of antibiotics used in severe, complicated infections caused by opportunistic multi-drug-resistant pathogens. This proves that the epidemiological situation was deteriorating on the area of PKW Afghanistan service mission. PMID:23285678

  15. The double life of antibiotics.

    PubMed

    Yap, Mee-Ngan F

    2013-01-01

    Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response. PMID:24003650

  16. Prospective audit and feedback on antibiotic prescription in an adult hematology-oncology unit in Singapore.

    PubMed

    Yeo, C-L; Chan, D S-G; Earnest, A; Wu, T-S; Yeoh, S-F; Lim, R; Jureen, R; Fisher, D; Hsu, L-Y

    2012-04-01

    We evaluated the impact of a prospective audit and feedback antimicrobial stewardship program (ASP) on antibiotic prescription and resistance trends in a hematology-oncology unit in a university hospital (National University Cancer Institute, Singapore [NCIS]). A prospective interrupted time-series study comprising 11-month pre-intervention (PIP) and intervention evaluation phases (IEP) flanking a one-month implementation phase was carried out. Outcome measures included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and all antibiotics (encompassing audited and non-audited antibiotics), and the incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital. There were 580 ASP recommendations from 1,276 audits, with a mean monthly compliance of 86.9%. Significant reversal of prescription trends towards reduced prescription of audited (coefficient = -2.621; 95% confidence interval [CI]: -4.923, -0.319; p = 0.026) and all evaluated antibiotics (coefficient = -4.069; 95% CI: -8.075, -0.063; p = 0.046) was observed. No changes were seen for both internal and external controls, except for the reversal of prescription trends for cephalosporins hospital-wide. Antimicrobial resistance did not change over the time period of the study. Adverse outcomes-the majority unavoidable-occurred following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be implemented in the complex setting of hematology-oncology inpatients. PMID:21845470

  17. [Resistance to antibiotics of bacteria involved in respiratory infections (author's transl)].

    PubMed

    Grassi, G G; Bucci, R

    1976-01-01

    The present status of resistance to antibiotics of bacteria involved in respiratory infections is reviewed. Schematically it can outlined as follows. Streptococcus B-haemolyticus as well as Pneumococcus did not change their sensitivity to penicillin, but some strains are now resistant to tetracycline. Streptococcus viridans, Enterococcus and H. influenzae did not change substantially their sensitivity to antibiotics. Staphylococcus aureus is the bacterial species that always poses some problems with regard to antibiotic resistance. Due to the selection of strains penicillinase-producing because of the large use of penicillin, the most part of clinical isolates of staphylococci is now resistant to penicillin. In addition an increased number of strains resistant to the other antibiotics has been registered as soon as they has been introduced in therapy. The resistant strains spread in a particularly rapid way in hospital. The introduction in therapy of penicillinase-resistant penicillins constituted a remarkable advance in therapy of staphylococcal infection. However, there is now a growing number of indications about the emergence of methicillin resistant strains of staphylococci. On the other hand it must be recalled that since 1960 a marked reduction of incidence and mortality in severe staphylococcal infections has been noted. Incidence and mortality of respiratory infections due to Gram-negative bacilli is augmented particularly in connection with a larger use of immunosuppressive and antineoplastic therapies, of particular surgical or reanimation procedures, of intensive courses of antibiotic therapy etc. Emergence of Pseudomonas, Proteus, Serratia, Providencia, etc. infections poses many difficult problems of chemotherapy since these species are scarcely sensitive to antibiotics. Carbenicillin, cephalosporins, sisomicin, tobramycin, amikacin are the more recent drugs that alone or in combination may offer some chances of success in this field. PMID:13744

  18. [Influence of the Parameter "The Rate of Administration" During the Test "Abnormal Toxicity" on Quality Control of Ceftriaxone an Antibiotic of the Cephalosporin Group].

    PubMed

    Sharoykina, M V; Ryabtseva, M S; Kovaleva, E L; Neugodova, N P

    2015-01-01

    The influence of the rate of administration was examined during the test "Abnormal toxicity" on the quality control of ceftriaxone in a comparative experimental study on the basis of the methodologies Rus. Ph. XII and Eur. Ph. Recommendations are issued for conducting study entitled "Abnormal toxicity" for the formulations of ceftriaxone. PMID:26168683

  19. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  20. A Qualitative Review on the Pharmacokinetics of Antibiotics in Saliva: Implications on Clinical Pharmacokinetic Monitoring in Humans.

    PubMed

    Kiang, Tony K L; Ensom, Mary H H

    2016-03-01

    We conducted a systematic search to describe the current state of knowledge regarding the utility of saliva for clinical pharmacokinetic monitoring (CPM) of antibiotics. Although the majority of identified studies lacked sufficient pharmacokinetic data needed to assign an appropriate suitability classification, most aminoglycosides, fluoroquinolones, macrolides, penicillins/cephalosporins, and tetracyclines are likely not suitable for CPM in saliva. No clear pattern of correlation was observed between physiochemical properties that favor drug distribution into saliva and the likelihood of the antibiotic being classified as suitable for CPM in saliva (and vice versa). Insufficient data were available to determine if pathophysiological conditions affected salivary distribution of antibiotics. Additional confirmatory data are required for drugs (especially in patients) that are deemed likely suitable for CPM in saliva because only a few studies were available and many focused only on healthy subjects. All studies identified had relatively small sample sizes and exhibited large variability. Very few studies reported salivary collection parameters (e.g., salivary flow, pH) that could potentially have some impact on drug distribution into saliva. The available data are heavily weighted on healthy subjects, and insufficient data were available to determine if pathophysiology had effects on saliva drug distribution. Some studies also lacked assay sensitivity for detecting antibiotics in saliva. Overall, this review can be useful to clinicians who desire an overview on the suitability of saliva for conducting CPM of specific antibiotics, or for researchers who wish to fill the identified knowledge gaps to move the science of salivary CPM further. PMID:26346776

  1. Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes

    PubMed Central

    Cobos-Trigueros, Nazaret; Solé, Mar; Castro, Pedro; Torres, Jorge Luis; Rinaudo, Mariano; De Lazzari, Elisa; Morata, Laura; Hernández, Cristina; Fernández, Sara; Soriano, Alex; Nicolás, José María; Mensa, Josep; Vila, Jordi; Martínez, José Antonio

    2016-01-01

    Objective To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes. Methods Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters. Results A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5–1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6–1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5–1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7–1.3). Conclusions A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality. PMID:26982807

  2. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed Central

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

  3. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

    PubMed Central

    2014-01-01

    Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Conclusions Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients. PMID:24405683

  4. Prevalence of extended-spectrum cephalosporin-resistant Escherichia coli in a farrowing farm: ST1121 clone harboring IncHI2 plasmid contributes to the dissemination of blaCMY-2

    PubMed Central

    Deng, Hui; Si, Hong-Bin; Zeng, Shu-Yi; Sun, Jian; Fang, Liang-Xing; Yang, Run-Shi; Liu, Ya-Hong; Liao, Xiao-Ping

    2015-01-01

    During a regular monitoring of antimicrobial resistance in a farrowing farm in Southern China, 117 Escherichia coli isolates were obtained from sows and piglets. Compared with the isolates from piglets, the isolates from sows exhibited higher resistance rates to the tested cephalosporins. Correspondingly, the total detection rate of the blaCMY-2/blaCTX-M genes in the sow isolates (34.2%) was also significantly higher than that of the piglet isolates (13.6%; p < 0.05). The blaCMY-2 gene had a relatively high prevalence (11.1%) in the E. coli isolates. MLST and PFGE analysis revealed the clonal spread of ST1121 E. coli in most (7/13) of the blaCMY-2-positive isolates. An indistinguishable IncHI2 plasmid harboring blaCMY-2 was also identified in each of the seven ST1121 E. coli isolates. Complete sequence analysis of this IncHI2 plasmid (pEC5207) revealed that pEC5207 may have originated through recombination of an IncHI2 plasmid with a blaCMY-2-carrying IncA/C plasmid like pCFSAN007427_01. In addition to blaCMY-2, pEC5207 also carried other resistance determinants for aminoglycosides (aacA7), sulfonamides (sul1), as well as heavy metals ions, such as Cu and Ag. The susceptibility testing showed that the pEC5207 can mediate both antibiotic and heavy metal resistance. This highlights the role of pEC5207 in co-selection of blaCMY-2-positive isolates under the selective pressure of heavy metals, cephalosporins, and other antimicrobials. In conclusion, clonal spread of an ST1121 type E. coli strain harboring an IncHI2 plasmid contributed to the dissemination of blaCMY-2 in a farrowing farm in Southern China. We also have determined the first complete sequence analysis of a blaCMY-2-carrying IncHI2 plasmid. PMID:26579110

  5. Enterobacteriaceae resistant to third-generation cephalosporins and quinolones in fresh culinary herbs imported from Southeast Asia.

    PubMed

    Veldman, Kees; Kant, Arie; Dierikx, Cindy; van Essen-Zandbergen, Alieda; Wit, Ben; Mevius, Dik

    2014-05-01

    Since multidrug resistant bacteria are frequently reported from Southeast Asia, our study focused on the occurrence of ESBL-producing Enterobacteriaceae in fresh imported herbs from Thailand, Vietnam and Malaysia. Samples were collected from fresh culinary herbs imported from Southeast Asia in which ESBL-suspected isolates were obtained by selective culturing. Analysis included identification by MALDI-TOF mass spectrometry, susceptibility testing, XbaI-PFGE, microarray, PCR and sequencing of specific ESBL genes, PCR based replicon typing (PBRT) of plasmids and Southern blot hybridization. In addition, the quinolone resistance genotype was characterized by screening for plasmid mediated quinolone resistance (PMQR) genes and mutations in the quinolone resistance determining region (QRDR) of gyrA and parC. The study encompassed fifty samples of ten batches of culinary herbs (5 samples per batch) comprising nine different herb variants. The herbs originated from Thailand (Water morning glory, Acacia and Betel leaf), Vietnam (Parsley, Asian pennywort, Houttuynia leaf and Mint) and Malaysia (Holy basil and Parsley). By selective culturing 21 cefotaxime resistant Enterobacteriaceae were retrieved. Array analysis revealed 18 isolates with ESBL genes and one isolate with solely non-ESBL beta-lactamase genes. Mutations in the ampC promoter region were determined in two isolates with PCR and sequencing. The isolates were identified as Klebsiella pneumoniae (n=9), Escherichia coli (n=6), Enterobacter cloacae complex (n=5) and Enterobacter spp. (n=1). All isolates tested were multidrug resistant. Variants of CTX-M enzymes were predominantly found followed by SHV enzymes. PMQR genes (including aac(6')-1b-cr, qnrB and qnrS) were also frequently detected. In almost all cases ESBL and quinolone resistance genes were located on the same plasmid. Imported fresh culinary herbs from Southeast Asia are a potential source for contamination of food with multidrug resistant bacteria. Because these herbs are consumed without appropriate heating, transfer to human bacteria cannot be excluded. PMID:24607424

  6. Molecular mechanisms of antibiotic resistance.

    PubMed

    Blair, Jessica M A; Webber, Mark A; Baylay, Alison J; Ogbolu, David O; Piddock, Laura J V

    2015-01-01

    Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics. PMID:25435309

  7. Prescribing for children - taste and palatability affect adherence to antibiotics: a review.

    PubMed

    Baguley, Dave; Lim, Emma; Bevan, Amanda; Pallet, Ann; Faust, Saul N

    2012-03-01

    The taste of an antibiotic is often not taken into account by practitioners, although there is significant evidence to show palatability correlates strongly with adherence. Many parents will be familiar with the difficulties of convincing young children to take bitter, unfamiliar medicine. Certain drugs, for example flucloxacillin, are so unpalatable that they should not be prescribed as syrups without prior 'taste testing' in an individual child, while others, such as oral cephalosporins, are accepted very well although they are more expensive with a broader antimicrobial spectrum than may be strictly necessary. Palatability is important in the broader context of global child health as regards the successful treatment of malaria, HIV and dehydration. The hidden cost of poor adherence resulting treatment failure, complications and the development of drug resistance cannot be over emphasised. Prescribing should involve parents, children and practitioners in an open discussion around the most suitable, palatable formulations for successful treatment outcomes. PMID:22088684

  8. Activity of N-formimidoyl thienamycin and cephalosporins against isolates from nosocomially acquired bacteremia.

    PubMed Central

    Gutiérrez-Núñez, J; Harrington, P T; Ramirez-Ronda, C H

    1982-01-01

    The in vitro activity of N-formimidoyl thienamycin was compared with that of seven beta-lactam agents against bacteremic clinical isolates, including gentamicin-resistant, gram-negative bacilli, Staphylococcus aureus, Staphylococcus epidermidis, streptococci, and enterococci. N-formimidoyl thienamycin was the most active antibiotic against all of the gram-positive cocci studied, with the exception of Staphylococcus epidermidis, and the only agent active against the enterococci. N-formimidoyl thienamycin was less active than some of the other agents against Enterobacteriaceae, except for the strains of Serratia and Citrobacter studied. For Pseudomonas aeruginosa, N-formimidoyl thienamycin was the most active agent (4 micrograms/ml was the lowest concentration that inhibited 90% of the strains tested). PMID:6954876

  9. Reviving old antibiotics.

    PubMed

    Theuretzbacher, Ursula; Van Bambeke, Françoise; Cantón, Rafael; Giske, Christian G; Mouton, Johan W; Nation, Roger L; Paul, Mical; Turnidge, John D; Kahlmeter, Gunnar

    2015-08-01

    In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to 're-develop' these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections. PMID:26063727

  10. The Comprehensive Antibiotic Resistance Database

    PubMed Central

    McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

    2013-01-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  11. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  12. Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and humans in the United States 2009

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment and ceftriaxone, an extended-spectrum cephalosporin, is commonly used in both adults and child...

  13. Rapid screening of multiple antibiotic residues in milk using disposable amperometric magnetosensors.

    PubMed

    Conzuelo, F; Ruiz-Valdepeas Montiel, V; Campuzano, S; Gamella, M; Torrente-Rodrguez, R M; Reviejo, A J; Pingarrn, J M

    2014-04-11

    Disposable amperometric magnetosensors, involving a mixture of modified-magnetic beads (MBs), for the multiplex screening of cephalosporins (CPHs), sulfonamides (SAs) and tetracyclines (TCs) antibiotic residues in milk are reported for the first time in this work. The multiplexed detection relies on the use of a mixture of target specific modified magnetic beads (MBs) and application of direct competitive assays using horseradish peroxidase (HRP)-labeled tracers. The amperometric responses measured at -0.20 V vs. the Ag pseudo-reference electrode of screen-printed carbon electrodes (SPCE) upon the addition of H2O2 in the presence of hydroquinone (HQ) as redox mediator, were used to monitor the extent of the different affinity reactions. The developed methodology, involving a simple and short pretreatment, allowed discrimination between no contaminated UHT and raw milk samples and samples containing antibiotic residues at the maximum residue limits (MRLs). The usefulness of the multiplexed magnetosensor was demonstrated by analyzing spiked milk samples in only 5 min. The results demonstrated that a clear discrimination of milk samples contaminated with antibiotics at their MRL level or their mixtures, allowing the identification of milk not complying with current legislation. These features make the developed methodology a promising alternative in the development of user-friendly devices for on-site analysis to ensure quality control for dairy products. PMID:24745735

  14. Determination of veterinary antibiotics in bovine urine by liquid chromatography-tandem mass spectrometry.

    PubMed

    Chiesa, Luca; Nobile, Maria; Arioli, Francesco; Britti, Domenico; Trutic, Natasa; Pavlovic, Radmila; Panseri, Sara

    2015-10-15

    A follow-up of antibiotics (tetracyclines, fluoroquinolones, cephalosporins, penicillins and amphenicols) in the bovine urine is important for two reasons: to understand if they are still present in organism, and whether their occurrence in urine might be considered as an environmental risk. A validated HPLC-MS/MS method (Decision 2002/657/EC) for antibiotics determination in bovine urine was developed. CCα and CCβ were in the range of 0.58-0.83 and 0.55-1.1 ng mL(-1), respectively. Recoveries were 92-108%, with inter-day repeatability below 12%. Analysis of bovine urine revealed frequent presence of tetracyclines, which was related with animal's age. The cause, most presumably, might be found in different therapeutic protocols applied for veal calves and young bulls enrolled in this study. Most abundant was oxytetracycline with highest level in veal calves (1718 ng mL(-1)) vs. young bulls (2.8 ng mL(-1)). Our results indicate the necessity of antibiotics monitoring in bovine urine before animals undergo further processing in the food industry. PMID:25952835

  15. Comparative in vitro activity of the new oral cephalosporin Bay v 3522 against aerobic and anaerobic bacteria.

    PubMed

    Rylander, M; Nord, C E; Norrby, S R

    1990-10-01

    The in vitro activity of the new oral cephalosporin Bay v 3522 against 229 aerobic and 330 anaerobic clinical isolates was determined using the agar dilution technique. For comparison, amoxicillin, amoxicillin/clavulanate, cefaclor, cefadroxil, cefuroxime, cephalexin, ciprofloxacin, clindamycin, co-trimoxazole, doxycycline, erythromycin and metronidazole (only anaerobic bacteria) were tested. Bay v 3522 was found to have high activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, anaerobic cocci, Propionibacterium acnes, Clostridium perfringens and fusobacteria. When tested against a higher inoculum or using the broth dilution technique, the activity of Bay v 3522 showed little dependence on inoculum size and the bactericidal activity was similar to inhibitory activity in most bacterial groups. Bay v 3522 may be useful in the treatment of skin, soft tissue and respiratory tract infections. Clinical studies are thus warranted. PMID:2261923

  16. Mutations in β-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins

    PubMed Central

    Berrazeg, M.; Jeannot, K.; Ntsogo Enguéné, Véronique Yvette; Broutin, I.; Loeffert, S.; Fournier, D.

    2015-01-01

    Mutation-dependent overproduction of intrinsic β-lactamase AmpC is considered the main cause of resistance of clinical strains of Pseudomonas aeruginosa to antipseudomonal penicillins and cephalosporins. Analysis of 31 AmpC-overproducing clinical isolates exhibiting a greater resistance to ceftazidime than to piperacillin-tazobactam revealed the presence of 17 mutations in the β-lactamase, combined with various polymorphic amino acid substitutions. When overexpressed in AmpC-deficient P. aeruginosa 4098, the genes coding for 20/23 of these AmpC variants were found to confer a higher (2-fold to >64-fold) resistance to ceftazidime and ceftolozane-tazobactam than did the gene from reference strain PAO1. The mutations had variable effects on the MICs of ticarcillin, piperacillin-tazobactam, aztreonam, and cefepime. Depending on their location in the AmpC structure and their impact on β-lactam MICs, they could be assigned to 4 distinct groups. Most of the mutations affecting the omega loop, the R2 domain, and the C-terminal end of the protein were shared with extended-spectrum AmpCs (ESACs) from other Gram-negative species. Interestingly, two new mutations (F121L and P154L) were predicted to enlarge the substrate binding pocket by disrupting the stacking between residues F121 and P154. We also found that the reported ESACs emerged locally in a variety of clones, some of which are epidemic and did not require hypermutability. Taken together, our results show that P. aeruginosa is able to adapt to efficacious β-lactams, including the newer cephalosporin ceftolozane, through a variety of mutations affecting its intrinsic β-lactamase, AmpC. Data suggest that the rates of ESAC-producing mutants are ≥1.5% in the clinical setting. PMID:26248364

  17. Mutations in β-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins.

    PubMed

    Berrazeg, M; Jeannot, K; Ntsogo Enguéné, Véronique Yvette; Broutin, I; Loeffert, S; Fournier, D; Plésiat, P

    2015-10-01

    Mutation-dependent overproduction of intrinsic β-lactamase AmpC is considered the main cause of resistance of clinical strains of Pseudomonas aeruginosa to antipseudomonal penicillins and cephalosporins. Analysis of 31 AmpC-overproducing clinical isolates exhibiting a greater resistance to ceftazidime than to piperacillin-tazobactam revealed the presence of 17 mutations in the β-lactamase, combined with various polymorphic amino acid substitutions. When overexpressed in AmpC-deficient P. aeruginosa 4098, the genes coding for 20/23 of these AmpC variants were found to confer a higher (2-fold to >64-fold) resistance to ceftazidime and ceftolozane-tazobactam than did the gene from reference strain PAO1. The mutations had variable effects on the MICs of ticarcillin, piperacillin-tazobactam, aztreonam, and cefepime. Depending on their location in the AmpC structure and their impact on β-lactam MICs, they could be assigned to 4 distinct groups. Most of the mutations affecting the omega loop, the R2 domain, and the C-terminal end of the protein were shared with extended-spectrum AmpCs (ESACs) from other Gram-negative species. Interestingly, two new mutations (F121L and P154L) were predicted to enlarge the substrate binding pocket by disrupting the stacking between residues F121 and P154. We also found that the reported ESACs emerged locally in a variety of clones, some of which are epidemic and did not require hypermutability. Taken together, our results show that P. aeruginosa is able to adapt to efficacious β-lactams, including the newer cephalosporin ceftolozane, through a variety of mutations affecting its intrinsic β-lactamase, AmpC. Data suggest that the rates of ESAC-producing mutants are ≥1.5% in the clinical setting. PMID:26248364

  18. Whole-genome phylogenomic heterogeneity of Neisseria gonorrhoeae isolates with decreased cephalosporin susceptibility collected in Canada between 1989 and 2013.

    PubMed

    Demczuk, Walter; Lynch, Tarah; Martin, Irene; Van Domselaar, Gary; Graham, Morag; Bharat, Amrita; Allen, Vanessa; Hoang, Linda; Lefebvre, Brigitte; Tyrrell, Greg; Horsman, Greg; Haldane, David; Garceau, Richard; Wylie, John; Wong, Tom; Mulvey, Michael R

    2015-01-01

    A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some N. gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic penA alleles, followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections. PMID:25378573

  19. Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

    PubMed Central

    Lynch, Tarah; Martin, Irene; Van Domselaar, Gary; Graham, Morag; Bharat, Amrita; Allen, Vanessa; Hoang, Linda; Lefebvre, Brigitte; Tyrrell, Greg; Horsman, Greg; Haldane, David; Garceau, Richard; Wylie, John; Wong, Tom; Mulvey, Michael R.

    2014-01-01

    A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some N. gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic penA alleles, followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections. PMID:25378573

  20. Rationalizing antibiotic use to limit antibiotic resistance in India+

    PubMed Central

    2011-01-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  1. Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012

    PubMed Central

    van der Steen, Matthijs; Leenstra, Tjalling; Kluytmans, Jan A. J. W.; van der Bij, Akke K.

    2015-01-01

    We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from different patient settings in The Netherlands from 20082012. E. coli and K. pneumoniae isolates from blood and urine samples of patients > = 18 years were selected from the Dutch Infectious Disease Surveillance System-Antimicrobial Resistance (ISIS-AR) database. We used multivariable Poisson regression to study the rate per year of blood stream infections by susceptible and resistant isolates, and generalized estimating equation (GEE) log-binomial regression for trends in the proportion of extended-spectrum cephalosporin-resistant isolates. Susceptibility data of 197,513 E. coli and 38,244 K. pneumoniae isolates were included. The proportion of extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates from urine and blood samples increased in all patient settings, except for K. pneumoniae isolates from patients admitted to intensive care units. For K. pneumoniae, there was a different time trend between various patient groups (p<0.01), with a significantly higher increase in extended-spectrum cephalosporin-resistant isolates from patients attending a general practitioner than in isolates from hospitalized patients. For E. coli, the increasing time trends did not differ among different patient groups. This nationwide study shows a general increase in extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates. However, differences in trends between E. coli en K. pneumoniae underline the importance of E. coli as a community-pathogen and its subsequent influence on hospital resistance level, while for K. pneumoniae the level of resistance within the hospital seems less influenced by the resistance trends in the community. PMID:26381746

  2. Predicting Antibiotic Resistance to Community-Acquired Pneumonia Antibiotics in Culture-Positive Patients With Healthcare-Associated Pneumonia

    PubMed Central

    Madaras-Kelly, Karl J.; Remington, Richard E.; Fan, Vincent S.; Sloan, Kevin L.

    2016-01-01

    OBJECTIVE To develop and validate a model to predict resistance to community-acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare-associated pneumonia (HCAP), and to compare the model’s predictive performance to a model including only guideline-defined criteria for HCAP. DESIGN Retrospective cohort study. SETTING Six Veterans Affairs Medical Centers in the northwestern United States. PATIENTS Culture-positive inpatients with HCAP. MEASUREMENTS Patients were identified based upon guideline-defined criteria for HCAP. Relevant cultures obtained within 48 hours of admission were assessed to determine bacteriology and antibiotic susceptibility. Medical records for the year preceding admission were assessed to develop predictive models of CAP-resistance with logistic regression. The predictive performance of cohort-developed and guideline-defined models was compared. RESULTS CAP-resistant organisms were identified in 118 of 375 culture-positive patients. Of guideline-defined criteria, CAP-resistance was associated (odds ratio (OR) [95% confidence interval (CI)]) with: admission from nursing home (2.6 [1.6–4.4]); recent antibiotic exposure (1.7 [1.0–2.8]); and prior hospitalization (1.6 [1.0–2.6]). In the cohort-developed model, CAP-resistance was associated with: admission from nursing home or recent nursing home discharge (2.3 [1.4–3.8]); positive methicillin-resistant Staphylococcus aureus (MRSA) history within 90 days of admission (6.4 [2.6–17.8]) or 91–365 days (2.3 [0.9–5.9]); cephalosporin exposure (1.8 [1.1–2.9]); recent infusion therapy (1.9 [1.0–3.5]); diabetes (1.7 [1.0–2.8]); and intensive care unit (ICU) admission (1.6 [1.0–2.6]). Area under the receiver operating characteristic curve (aROC [95% CI]) for the cohort-developed model (0.71 [0.65–0.77]) was significantly higher than for the guideline-defined model (0.63 [0.57–0.69]) (P = 0.01). CONCLUSIONS Select guideline-defined criteria predicted CAP-resistance. A cohort-developed model based primarily on prior MRSA history, nursing home residence, and specific antibiotic exposures provided improved prediction of CAP-resistant organisms in HCAP. PMID:22038859

  3. The erratic antibiotic susceptibility patterns of bacterial pathogens causing urinary tract infections

    PubMed Central

    Ahmed, Iftkhar; Sajed, Muhammad; Sultan, Aneesa; Murtaza, Iram; Yousaf, Sohail; Maqsood, Bushra; Vanhara, Petr; Anees, Mariam

    2015-01-01

    Increasing trend of antibiotic resistance and expression of Extended Spectrum Beta Lactamases (ESBLs) are serious threats for public health as they render the treatment ineffective. Present study was designed to elucidate the antibiotic-susceptibility patterns of ESBL and non-ESBL producing E. coli and K. pneumoniae causing urinary tract infections so that the ineffective antibiotics could be removed from the line of treatment. The bacterial isolates obtained from the urine of patients visiting a tertiary health care facility were cultured for strain identification using API20E. Antimicrobial susceptibility and ESBL detection were done by Kirby-bauer diffusion technique. Almost 53.4 % isolates of E. coli and 24.5 % isolates of K. pneumoniae were found to be ESBL producers. The ESBL producing bacteria were found to be more resistant towards various antibiotics. The most effective drugs against E. coli ESBL isolates were imipenem (99.54 %), ampicillin-sulbactam (97.48 %), piperacillin-tazobactam (96.86 %), fosfomycin (94.51 %), amikacin (92.26 %) and nitrofurantoin (90.68 %). The most effective drugs against K. pneumoniae ESBL isolates were imipenem (97.62 %), piperacillin-tazobactam (95.35 %), ampicillin-sulbactam (90.48 %) and amikacin (88.37 %). The antibiotics having the highest resistance, particularly by the ESBL producers were amoxicillin clavulanic acid, sulphamethoxalzole/ trimethoprim, cefuroxime, cefpirome, ceftriaxone and ciprofloxacin. Most of the isolates showed multi drug resistance (MDR). High frequency of ESBL producing E. coli and K. pneumoniae were observed as compared to previous data. Penicillins, cephalosporins and some representatives of fluoroquinolones were least effective against the common UTIs and are recommended to be removed from the line of treatment. PMID:26648826

  4. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    PubMed

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. PMID:24919144

  5. The erratic antibiotic susceptibility patterns of bacterial pathogens causing urinary tract infections.

    PubMed

    Ahmed, Iftkhar; Sajed, Muhammad; Sultan, Aneesa; Murtaza, Iram; Yousaf, Sohail; Maqsood, Bushra; Vanhara, Petr; Anees, Mariam

    2015-01-01

    Increasing trend of antibiotic resistance and expression of Extended Spectrum Beta Lactamases (ESBLs) are serious threats for public health as they render the treatment ineffective. Present study was designed to elucidate the antibiotic-susceptibility patterns of ESBL and non-ESBL producing E. coli and K. pneumoniae causing urinary tract infections so that the ineffective antibiotics could be removed from the line of treatment. The bacterial isolates obtained from the urine of patients visiting a tertiary health care facility were cultured for strain identification using API20E. Antimicrobial susceptibility and ESBL detection were done by Kirby-bauer diffusion technique. Almost 53.4 % isolates of E. coli and 24.5 % isolates of K. pneumoniae were found to be ESBL producers. The ESBL producing bacteria were found to be more resistant towards various antibiotics. The most effective drugs against E. coli ESBL isolates were imipenem (99.54 %), ampicillin-sulbactam (97.48 %), piperacillin-tazobactam (96.86 %), fosfomycin (94.51 %), amikacin (92.26 %) and nitrofurantoin (90.68 %). The most effective drugs against K. pneumoniae ESBL isolates were imipenem (97.62 %), piperacillin-tazobactam (95.35 %), ampicillin-sulbactam (90.48 %) and amikacin (88.37 %). The antibiotics having the highest resistance, particularly by the ESBL producers were amoxicillin clavulanic acid, sulphamethoxalzole/ trimethoprim, cefuroxime, cefpirome, ceftriaxone and ciprofloxacin. Most of the isolates showed multi drug resistance (MDR). High frequency of ESBL producing E. coli and K. pneumoniae were observed as compared to previous data. Penicillins, cephalosporins and some representatives of fluoroquinolones were least effective against the common UTIs and are recommended to be removed from the line of treatment. PMID:26648826

  6. Degradation kinetics and mechanism of ?-lactam antibiotics by the activation of H2O2 and Na2S2O8 under UV-254nm irradiation.

    PubMed

    He, Xuexiang; Mezyk, Stephen P; Michael, Irene; Fatta-Kassinos, Despo; Dionysiou, Dionysios D

    2014-08-30

    The extensive production and usage of antibiotics have led to an increasing occurrence of antibiotic residuals in various aquatic compartments, presenting a significant threat to both ecosystem and human health. This study investigated the degradation of selected ?-lactam antibiotics (penicillins: ampicillin, penicillin V, and piperacillin; cephalosporin: cephalothin) by UV-254nm activated H2O2 and S2O8(2-) photochemical processes. The UV irradiation alone resulted in various degrees of direct photolysis of the antibiotics; while the addition of the oxidants improved significantly the removal efficiency. The steady-state radical concentrations were estimated, revealing a non-negligible contribution of hydroxyl radicals in the UV/S2O8(2-) system. Mineralization of the ?-lactams could be achieved at high UV fluence, with a slow formation of SO4(2-) and a much lower elimination of total organic carbon (TOC). The transformation mechanisms were also investigated showing the main reaction pathways of hydroxylation (+16Da) at the aromatic ring and/or the sulfur atom, hydrolysis (+18Da) at the ?-lactam ring and decarboxylation (-44Da) for the three penicillins. Oxidation of amine group was also observed for ampicillin. This study suggests that UV/H2O2 and UV/S2O8(2-) advanced oxidation processes (AOPs) are capable of degrading ?-lactam antibiotics decreasing consequently the antibiotic activity of treated waters. PMID:25086235

  7. A Response Regulator from a Soil Metagenome Enhances Resistance to the β-Lactam Antibiotic Carbenicillin in Escherichia coli

    PubMed Central

    Allen, Heather K.; An, Ran; Handelsman, Jo; Moe, Luke A.

    2015-01-01

    Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16) harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins), rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs) that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology. PMID:25782011

  8. A response regulator from a soil metagenome enhances resistance to the β-lactam antibiotic carbenicillin in Escherichia coli.

    PubMed

    Allen, Heather K; An, Ran; Handelsman, Jo; Moe, Luke A

    2015-01-01

    Functional metagenomic analysis of soil metagenomes is a method for uncovering as-yet unidentified mechanisms for antibiotic resistance. Here we report an unconventional mode by which a response regulator derived from a soil metagenome confers resistance to the β-lactam antibiotic carbenicillin in Escherichia coli. A recombinant clone (βlr16) harboring a 5,169 bp DNA insert was selected from a metagenomic library previously constructed from a remote Alaskan soil. The βlr16 clone conferred specific resistance to carbenicillin, with limited increases in resistance to other tested antibiotics, including other β-lactams (penicillins and cephalosporins), rifampin, ciprofloxacin, erythromycin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin. Resistance was more pronounced at 24°C than at 37°C. Zone-of-inhibition assays suggested that the mechanism of carbenicillin resistance was not due to antibiotic inactivation. The DNA insert did not encode any genes known to confer antibiotic resistance, but did have two putative open reading frames (ORFs) that were annotated as a metallopeptidase and a two-component response regulator. Transposon mutagenesis and subcloning of the two ORFs followed by phenotypic assays showed that the response regulator gene was necessary and sufficient to confer the resistance phenotype. Quantitative reverse transcriptase PCR showed that the response regulator suppressed expression of the ompF porin gene, independently of the small RNA regulator micF, and enhanced expression of the acrD, mdtA, and mdtB efflux pump genes. This work demonstrates that antibiotic resistance can be achieved by the modulation of gene regulation by heterologous DNA. Functional analyses such as these can be important for making discoveries in antibiotic resistance gene biology and ecology. PMID:25782011

  9. The complex clinical picture of beta-lactam hypersensitivity: penicillins, cephalosporins, monobactams, carbapenems, and clavams.

    PubMed

    Torres, Maria J; Blanca, Miguel

    2010-07-01

    Beta-lactam antibiotics are the drugs most frequently involved in drug hypersensitivity reactions that are mediated by specific immunologic mechanisms. In addition to benzylpenicillin, several chemical structures belonging to 5 major subgroups can induce reactions. The most relevant structure is that of the amoxicillin molecule. Reactions belong to the 4 major mechanisms described by Coombs and Gell, whereby type IV reactions have recently been further subclassified. The most frequent reactions are type I, which are IgE mediated, and type IV, which are nonimmediate and T-cell dependent. IgE-specific antibodies may recognize the benzylpenicilloyl structure or another part of the molecule, such as the side chain, as antigenic determinants. Depending on specific recognition, subjects can be either cross-reactors or selective responders. A variety of entities exist in T-cell reactions, ranging from mild exanthema to life-threatening, severe reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Diagnostic tests for IgE-mediated reactions can be done in vivo by testing skin with different penicillin determinants or in vitro by quantitating specific IgE antibodies. For nonimmediate reactions, there are also in vitro and in vivo tests, with variable degrees of sensitivity and specificity. The natural history of IgE-mediated reactions indicates that the count of specific IgE antibodies decreases over time and that results of diagnostic tests can become negative. PMID:20609864

  10. Antibiotic resistance in pediatric urology

    PubMed Central

    Copp, Hillary L.

    2014-01-01

    Antibiotics are a mainstay in the treatment of bacterial infections, though their use is a primary risk factor for the development of antibiotic resistance. Antibiotic resistance is a growing problem in pediatric urology as demonstrated by increased uropathogen resistance. Lack of urine testing, nonselective use of prophylaxis, and poor empiric prescribing practices exacerbate this problem. This article reviews antibiotic utilization in pediatric urology with emphasis on modifiable practice patterns to potentially help mitigate the growing rates of antibiotic resistance. This includes urine testing to only treat when indicated and tailor broad-spectrum therapy as able; selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis with counseling regarding the importance of compliance; and using local antiobiograms, particularly pediatric-specific antiobiograms, with inpatient versus outpatient data. PMID:24688601

  11. [Monitoring antibiotic resistance in Argentina. The WHONET program, 1995-1996].

    PubMed

    Rossi, A; Tokumoto, M; Galas, M; Soloaga, R; Corso, A

    1999-10-01

    The World Health Organization has implemented a surveillance program for antimicrobial resistance that is known as WHONET. In Argentina the program was developed through a network of 23 public and private hospitals that participate in national and international quality-control programs. Between January 1995 and December 1996, the antimicrobial susceptibility of 16,073 consecutive clinical isolates was determined, using the recommended standards of the National Committee for Clinical Laboratory Standards of the United States of America. More than half of the Escherichia coli urinary isolates were resistant to ampicillin and more than 30% to trimethoprim/sulfamethoxazole (SXT). When the percentage of resistant isolates from outpatients (OPs) was compared to that observed in hospitalized patients (HPs), a marked difference in antimicrobial activity was noted in the case of gentamicin (2% from OPs resistant vs. 8% from HPs resistant), norfloxacin (2% vs. 6%), and third-generation cephalosporins (7% vs. 15%). Of the Klebsiella pneumoniae isolates recovered from blood cultures, 71% and 60% showed resistance to third-generation cephalosporins and to gentamicin, respectively. The overall rate of oxacillin resistance in Staphylococcus aureus was 39%. Around half of the Enterococcus spp. isolates showed high resistance to aminoglycosides, but resistance to glycopeptides was not found. In Argentina, ampicillin and SXT were not suitable for treating diarrhea. Shigella flexneri had a higher number of isolates resistant to both of those drugs (87% and 74%, respectively) than Sh. sonnei did (47% and 71%, respectively). About 40% of the Salmonella spp. isolated in pediatric hospitals were resistant to third-generation cephalosporins. When microorganisms causing bacterial meningitis were examined, Streptococcus pneumoniae showed a resistance rate of 18% to penicillin and Haemophilus influenzae a resistance rate of 19% to ampicillin. These rates are within the intermediate range reported for other countries of the Americas and for Europe. PMID:10572473

  12. Liquid antibiotics in bone cement

    PubMed Central

    Chang, Y. H.; Tai, C. L.; Hsu, H. Y.; Hsieh, P. H.; Lee, M. S.; Ueng, S. W. N.

    2014-01-01

    Objectives The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246–51. PMID:25104836

  13. [Pathways for surgical antibiotic prophylaxis].

    PubMed

    Maio, Patrizia

    2003-09-01

    Surgical site infections (SSIs) are a notable cause of hospital morbidity and mortality. Antibiotic prophylaxis has demonstrated a significant reduction in infection rate in clean-contaminated surgery and in clean surgery to a limited extent. To make antibiotic prophylaxis effective it is necessary to choose the right antibiotic, to administer it preoperatively and maintain sufficient serum and tissue levels through the operation. Open issues remain: antibiotic prophylaxis duration in prosthetic surgery, its use in hernia repair, breast surgery and mini-invasive surgery. PMID:14985643

  14. Applications of medical informatics in antibiotic therapy.

    PubMed

    Evans, R S; Pestotnik, S L

    1994-01-01

    The Infectious Disease Society of America is concerned about the excessive and inappropriate use of antibiotics in U.S. hospitals. Applications of Medical Informatics can help improve the use of antibiotics and help improve patient care by monitoring and managing enormous amounts of patient information. Monitoring the duration of every antibiotic ordered in the hospital or keeping tract of the antibiotic susceptibilities for five years are examples of tasks better performed by computers. The impact of computers in medicine is seen by some as disappointing. The computer revolution has not had the impact in medicine experienced by other areas. The acceptance and use of computers by medicine will be evolutionary rather than revolutionary. In 1979, the MYCIN project demonstrated that the computer could aid physicians in the selection of antibiotics. However, MYCIN was never clinically used because physicians were require to enter all patient information into the computer. The development of computerized medical records is an essential step to further the development and implementation of computer-aided decision support. The science of Medical Informatics is still relatively new but is emerging as a distinct academic field. A few hospitals are now installing information systems and have determined that these systems will play an essential role in their ability to survive into the next century. The telephone and the automobile have been recognized as two of the most important tools for improving medical care during the past 100 years. People could more readily get medical care and the time to transmit medical information was greatly reduced through physician use of the telephone and automobile. The computer is a tool that can be used to help physicians manage the great amount of medical information being generated every day. The computer can also alert the physician of patient conditions that need attention. However, it is the physician who must use and apply the computer provided information. Thus, the computer will assist but not replace physicians in providing medical care. PMID:8209811

  15. New Antibiotic Dosing

    PubMed Central

    Pineda, Leslie C.; Watt, Kevin M.

    2015-01-01

    Infection is common in premature infants and can cause significant morbidity and mortality. To prevent these devastating consequences, most infants admitted to the neonatal intensive care unit (NICU) are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. Despite legislation promoting and, in some cases, requiring pediatric drug studies, infants remain therapeutic orphans who often receive drugs "off-label" without data from clinical trials. Pharmacokinetic (PK) studies in premature infants have been scarce due to low study consent rates; limited blood volume available to conduct PK studies; difficulty in obtaining blood from infants; limited use of sensitive, low-volume drug concentration assays; and a lack of expertise in pediatric modeling and simulation. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, PK modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, PK data and dosing regimens for infants are now available for antibiotics commonly used in the NICU, including ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam. The discrepancy between previous dosing recommendations extrapolated from adult data and newer dosing regimens based on infant PK studies highlights the need to conduct PK studies in premature infants. PMID:25678003

  16. Antibiotic resistance of biofilms.

    PubMed

    Foley, I; Gilbert, P

    1996-01-01

    Microbial biofilms are notably recalcitrant towards treatment with antibiotics, biocides or disinfectants that would adequately control the same organisms growing in planktonic mode. Much of this resistance has been attributed to an organisation of the biofilm cells within exopolymer matrices. Whilst such exopolymers are unlikely to hinder the diffusion and access of antimicrobial agents to the underlying cells, they will chemically quench reactive biocides such as chlorine and peroxygens, and bind highly charged antibiotics, such as tobramycin and gentamycin, thereby providing some protection to the more deep lying cells. Extracellular enzymes, bound within the glycocalyx and able to degrade the treatment agents, will further reduce the access of susceptible compounds. Diffusion limitation however, is unlikely to be the sole moderator of the resistance properties of microbial biofilms. In addition, gradients of oxygen and nutrients established across the biofilm community will cause growth rates to be much reduced at points remoted from the accessible nutrient. Slow growth rates, and the associated induction of stringent responses further contribute towards this resistance. Finally, there have been recent demonstrations that attachment of microorganisms to surfaces promotes the expression of genes that are not normally expressed in planktonic culture. Whether or not the expression of such genes alters the phenotype in a manner which alters the response of the cells to antimicrobial agents remains to be demonstrated. PMID:22115185

  17. Antibiotic production in space

    NASA Astrophysics Data System (ADS)

    Klaus, David; Brown, Robert; Cierpik, Kim

    1998-01-01

    A wide variety of previous experiments have indicated that the space flight environment has a positive influence on the proliferation of microorganisms. Based on this premise, it was hypothesized that the production of secondary metabolites (specifically antibiotics) would also be increased as a consequence of the enhanced growth. Pilot studies performed onboard two shuttle missions to date have indicated that microbial antibiotic production was significantly increased in space grown colonies relative to comparable, matched ground controls. The practical application of these preliminary findings is being investigated. The empirical data are being analyzed in an attempt to establish specific gravity-dependent cause and effect relationships. An analytical model is being developed to further establish how physical principles might give rise to the various physiological responses observed to be altered in space. The envisioned commercial applications stemming from the unique knowledge of how gravity affects natural processes range from developing methods for increasing terrestrial pharmaceutic production efficiency to, ultimately perhaps, the design of economically feasible, space-borne fermentation and bioprocessing platforms.

  18. Counteraction of antibiotic production and degradation stabilizes microbial communities.

    PubMed

    Kelsic, Eric D; Zhao, Jeffrey; Vetsigian, Kalin; Kishony, Roy

    2015-05-28

    A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity, and in particular how antibiotic-producing, -sensitive and -resistant species coexist. While cyclic rockpaperscissors interactions can stabilize communities in spatial environments, coexistence in unstructured environments remains unexplained. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on three-way interactions in which an antibiotic-degrading species attenuates the inhibitory interactions between two other species. These interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by cheating species that cease to produce or degrade antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamic behaviours ranging from stable fixed points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatially structured and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity. PMID:25992546

  19. Counteraction of antibiotic production and degradation stabilizes microbial communities

    PubMed Central

    Kelsic, Eric D.; Zhao, Jeffrey; Vetsigian, Kalin; Kishony, Roy

    2015-01-01

    Summary A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity1-8, and in particular how antibiotic producing, sensitive and resistant species coexist9-15. While cyclic “rock-paper-scissors” interactions can stabilize communities in spatial environments9-11, coexistence in unstructured environments remains an enigma12,16. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on 3-way interactions where an antibiotic degrading species attenuates the inhibitory interactions between two other species. These 3-way interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by “cheating” species that cease producing or degrading antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamical behaviors ranging from stable fixed-points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatial and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity. PMID:25992546

  20. Role of antibiotic stewardship in extending the age of modern medicine.

    PubMed

    Mendelson, M

    2015-05-01

    Antibiotic resistance is threatening modern medicine. Overuse and misuse of antibiotics is driving resistance to such an extent that we have entered the post-antibiotic era, where some multidrug- and pandrug-resistant bacterial infections are no longer treatable. If the situation is not reversed,10 million people will die annually of drug-resistant infections by 2050. More than just a question of mortality, such infections are causing the closure of wards, cancellation of operations, and interference with other common medical procedures that rely on antibiotics for their success. The response to this crisis requires co-ordinated international action with increased surveillance of bacterial resistance, infection prevention, and antibiotic stewardship, i.e. access to affordable, quality-assured antibiotics prescribed appropriately. This review describes antibiotic stewardship at the individual patient and programmatic level, which must be adopted by every prescriber if we are to preserve modern medicine for future generations. PMID:26242674

  1. Antibiotic use in livestock production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic usage is a useful and commonly implemented practice in livestock and production agriculture that has progressively gained attention in recent years from consumers of animal products due to concerns about human and environmental health. Sub-therapeutic usage of antibiotics has led to a con...

  2. Biotherapeutics as alternatives to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

  3. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how

  4. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  5. Influence of therapeutic ceftiofur treatments of feedlot cattle on fecal and hide prevalences of commensal Escherichia coli resistant to expanded-spectrum cephalosporins, and molecular characterization of resistant isolates.

    PubMed

    Schmidt, John W; Griffin, Dee; Kuehn, Larry A; Brichta-Harhay, Dayna M

    2013-04-01

    In the United States, the blaCMY-2 gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum-cephalosporin-resistant (ESC(r)) Escherichia coli strains from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in cattle may increase the prevalence of ESC(r) E. coli. We report that herd ESC(r) E. coli fecal and hide prevalences throughout the residency of cattle at a feedlot, including during the period of greatest ceftiofur use at the feedlot, were either not significantly different (P ? 0.05) or significantly less (P < 0.05) than the respective prevalences at arrival. Longitudinal sampling of cattle treated with ceftiofur demonstrated that once the transient increase of ESC(r) E. coli shedding that follows ceftiofur injection abated, ceftiofur-injected cattle were no more likely than untreated members of the same herd to shed ESC(r) E. coli. Pulsed-field gel electrophoresis (PFGE) genotyping, antibiotic resistance phenotyping, screening for presence of the blaCMY-2 gene, and plasmid replicon typing were performed on 312 ESC(r) E. coli isolates obtained during six sampling periods spanning the 10-month residence of cattle at the feedlot. The identification of only 26 unique PFGE genotypes, 12 of which were isolated during multiple sampling periods, suggests that clonal expansion of feedlot-adapted blaCMY-2 E. coli strains contributed more to the persistence of blaCMY-2 than horizontal transfer of IncA/C plasmids between E. coli strains at this feedlot. We conclude that therapeutic use of ceftiofur at this cattle feedlot did not significantly increase the herd prevalence of ESC(r) E. coli. PMID:23354706

  6. [Antibiotic resistance: A global crisis].

    PubMed

    Als, Juan-Ignacio

    2015-12-01

    The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics. PMID:25475657

  7. Antibiotics from neglected bacterial sources.

    PubMed

    Pidot, Sacha J; Coyne, Sbastien; Kloss, Florian; Hertweck, Christian

    2014-01-01

    The current crop of antibiotics in clinical use are either natural products or their derivatives. However, the rise of a multitude of different antibiotic resistant human pathogens has meant that new antibiotics are urgently needed. Unfortunately, the search for new antibiotics from traditional bacterial sources often results in a high rediscovery rate of known compounds and a low chance of identifying truly novel chemical entities. To overcome this, previously unexplored (or under investigated) bacterial sources are being tapped for their potential to produce novel compounds with new activities. Here, we review a number of antibiotic compounds identified from bacteria of the genera Burkholderia, Clostridium, Lysobacter, Pantoea and Xenorhabdus and describe the potential of organisms and their associated metabolites in future drug discovery efforts. PMID:24120363

  8. A call for antibiotic alternatives research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The persistence and spread of antibiotic resistance and decreased profitability of new antibiotics have created the dangerous prospect of ineffective therapies against bacterial diseases. The discovery, development, and application of effective antibiotic alternatives, especially in agriculture, sho...

  9. Danger of Antibiotic Overuse (For Parents)

    MedlinePLUS

    ... against them. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires higher doses of ... to even the most powerful antibiotics available today. Antibiotic resistance is a widespread problem, and one that the ...

  10. Danger of Antibiotic Overuse (For Parents)

    MedlinePLUS

    ... Bullies Pregnant? What to Expect The Danger of Antibiotic Overuse KidsHealth > Parents > Flu Center > Treatment > The Danger ... by not reaching for the prescription pad. How Antibiotics Work Antibiotics, first used in the 1940s, are ...

  11. Community-Onset Escherichia coli Infection Resistant to Expanded-Spectrum Cephalosporins in Low-Prevalence Countries

    PubMed Central

    Ingram, Paul R.; Runnegar, Naomi; Pitman, Matthew C.; Freeman, Joshua T.; Athan, Eugene; Havers, Sally M.; Sidjabat, Hanna E.; Jones, Mark; Gunning, Earleen; De Almeida, Mary; Styles, Kaylene; Paterson, David L.

    2014-01-01

    By global standards, the prevalence of community-onset expanded-spectrum-cephalosporin-resistant (ESC-R) Escherichia coli remains low in Australia and New Zealand. Of concern, our countries are in a unique position, with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbors with high ESC-R E. coli rates. We aimed to characterize the risks and dynamics of community-onset ESC-R E. coli infection in our low-prevalence region. A case-control methodology was used. Patients with ESC-R E. coli or ESC-susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary care hospitals in Australia and New Zealand. Epidemiological data were prospectively collected, and bacteria were retained for analysis. In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R among E. coli strains, including birth on the Indian subcontinent (odds ratio [OR] = 11.13, 95% confidence interval [95% CI] = 2.17 to 56.98, P = 0.003), urinary tract infection in the past year (per-infection OR = 1.430, 95% CI = 1.13 to 1.82, P = 0.003), travel to southeast Asia, China, the Indian subcontinent, Africa, and the Middle East (OR = 3.089, 95% CI = 1.29 to 7.38, P = 0.011), prior exposure to trimethoprim with or without sulfamethoxazole and with or without an expanded-spectrum cephalosporin (OR = 3.665, 95% CI = 1.30 to 10.35, P = 0.014), and health care exposure in the previous 6 months (OR = 3.16, 95% CI = 1.54 to 6.46, P = 0.02). Among our ESC-R E. coli strains, the blaCTX-M ESBLs were dominant (83% of ESC-R E. coli strains), and the worldwide pandemic ST-131 clone was frequent (45% of ESC-R E. coli strains). In our low-prevalence setting, ESC-R among community-onset E. coli strains may be associated with both export from health care facilities into the community and direct import into the community from high-prevalence regions. PMID:24468775

  12. Cephalosporin C production by a highly productive Cephalosporium acremonium strain in an airlift tower loop reactor with static mixers.

    PubMed

    Zhou, W; Holzhauer-Rieger, K; Bayer, T; Schgerl, K

    1993-04-01

    The production of cephalosporin C (CPC) and its precursors penicillin N (PEN N), deacetoxycephalosporin C (DAOC) and deacetylcephalosporin C (DAC), with a highly productive strain of Cephalosporin acremonium, was investigated in an 80-1 airlift tower loop reactor with four static mixer modules (Type SMV, Sulzer) (ATLRM) on a complex medium containing 50 g l-1 peanut flour (PF). The most important key parameters such as glucose concentration and cell mass concentration were monitored during a fed-batch cultivation process. The concentrations of products CPC, PEN N, DAOC an DAC were determined on line by HPLC. The influences of four motionless mixers on the dissolved oxygen concentration (DOC), oxygen transfer rate, the cell growth and the CPC production, as well as the reactor performance, were evaluated. The results were compared with the performance of an airlift tower loop reactor (ATLR) without static mixers as well as with a stirred tank reactor (STR). A comparison of cultivations in the ATLRM and ATLR with 50 g l-1 PF indicates that the obtained maximal CPC concentration and the (CPC + DAC + DAOC) concentration were 7% and 22% higher in the ATLRM (4.96 and 7.46 g l-1) than in the ATLR (4.63 and 6.13 g l-1) respectively. The maximal CPC volumetric productivity in the ATLRM (55.1 mg l-1 h-1) was also considerably higher than that in the ATLR (48.5 mg l-1 h-1). The specific power input was reduced from 2.36 to 1.5 kW m-3, the specific productivity pertaining to the power input was improved from 1.96 to 3.31 g W-1. On the other hand, cultivation in the ATLRM had a lower maximum CPC concentration and volumetric productivity than those in STR (7.2 g l-1 and 71.2 mg l-1 h-1) with the same medium due to the lower shear stress levels and the lower specific power input (1.5 vs. 3.0 kW m-3); but the specific power imput-based yield coefficient was in the ATLRM (3.31 g W-1) higher than in the STR (2.40 g W-1). By increasing the amount of PF, it was possible to enhance the CPC concentration and volumetric productivity in the STR. However, the performance of the ATLRM was limited to using a medium containing maximal 50 g l-1 PF because of the high viscosity of the medium, the limited energy input and thus the limited oxygen supply. PMID:7763560

  13. Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance

    PubMed Central

    Yap, Polly Soo Xi; Yiap, Beow Chin; Ping, Hu Cai; Lim, Swee Hua Erin

    2014-01-01

    For many years, the battle between humans and the multitudes of infection and disease causing pathogens continues. Emerging at the battlefield as some of the most significant challenges to human health are bacterial resistance and its rapid rise. These have become a major concern in global public health invigorating the need for new antimicrobial compounds. A rational approach to deal with antibiotic resistance problems requires detailed knowledge of the different biological and non-biological factors that affect the rate and extent of resistance development. Combination therapy combining conventional antibiotics and essential oils is currently blooming and represents a potential area for future investigations. This new generation of phytopharmaceuticals may shed light on the development of new pharmacological regimes in combating antibiotic resistance. This review consolidated and described the observed synergistic outcome between essential oils and antibiotics, and highlighted the possibilities of essential oils as the potential resistance modifying agent. PMID:24627729

  14. [The physician, patient and antibiotics].

    PubMed

    Pechre, Jean-Claude

    2004-01-01

    More than 3.000 randomized patients, who received an antibiotic course for a mild respiratory infection in the last 2 months have been interviewed in 4 European countries about their perceptions of antibiotic therapy and the doctor's skills. Six attitudinal dimensions related to the doctor identified 4 patients type: Involved (30 %), Deferents (23%), Ignored (13%) and Critical (17%). Involved and Deferent patients knew better the rules of good antibiotic use (p<0,01), were more compliant (p<0,01), and received more accurater information from the doctor (p<0,01). Ignored patients keep left over antibiotics for uncontrolled further use most often (p<0,01). A large majority of patients, whatever the category, believed that a flu should be treated with an antibiotic. Germany includes more involved patients, the highest rate of confidence in physician's skills, who was the most informative, but they also had less people knowing the uselessness of antibiotics in flu. Spaniards had more propensity to expect antibiotics from their doctor, showed the lesser level of confidence in their physician's skill, and were the most prone to claim for the benign character of their infection. Critical patients were mostly recruited in France and Italy which also includes the highest rate of ignored patients. French patients were by far the less likely to receive accurate information from their physician. In conclusion, an actual educational deficit has been found in the patients regarding antibiotic use. The physician is in the best position for correcting the deficit. By implicating more the patients in the medical decision, he or she will deflate the ignored category, the most likely to misuse antibiotics, and hence to produce antibiotic resistance. PMID:15918656

  15. Antibiotic-resistant bacteria: a challenge for the food industry.

    TOXLINE Toxicology Bibliographic Information

    Capita R; Alonso-Calleja C

    2013-01-01

    Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed.

  16. Antibiotic-resistant bacteria: a challenge for the food industry.

    PubMed

    Capita, Rosa; Alonso-Calleja, Carlos

    2013-01-01

    Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed. PMID:23035919

  17. New uses of older antibiotics.

    PubMed

    Klein, N C; Cunha, B A

    2001-01-01

    Despite the development of extended-spectrum penicillins, cephalosporins, and quinolones, the older antimicrobial agents, doxycycline, minocycline, TMP-SMX, clindamycin, and metronidazole, still play an important role in the treatment of infectious diseases. All of these older drugs are well absorbed by the oral route, attaining serum levels equivalent to those achieved by parenteral administration. The availability of generic forms of the older drugs reduces their cost. Besides traditional uses, some older drugs have become the preferred therapy for newly recognized infectious diseases. Doxycycline is the preferred drug for rickettsial tickborne diseases, ehrlichiosis and early Lyme disease. TMP-SMX is the preferred drug for I. belli and Cyclospora. Minocycline has been used to treat MRSA and MRSE infections. Clindamycin or metronidazole combined with a quinolone is an excellent oral regimen for polymicrobial infections. [table: see text] PMID:11190348

  18. Cephalosporin-sensitive penicillin-binding proteins of Staphylococcus aureus and Bacillus subtilis active in the conversion of [14C]penicillin G to [14C]phenylacetylglycine.

    PubMed

    Waxman, D J; Strominger, J L

    1979-12-10

    Breakdown of the covalent complex formed between [14C]penicillin G and higher molecular weight, cephalosporin-sensitive penicillin-binding proteins was studied using mixtures of the purified proteins isolated from membranes of Staphylococcus aureus and Bacillus subtilis. These penicillin-binding proteins were found to release the bound 14C label in a first order process characterized by half-lives of 10 to 300 min at 37 degrees C. Denaturation of the penicilloyl.penicillin-binding proctein complex prevented this release, indicating that the process is enzyme-catalyzed. [14C]Phenylacetylglycine was identified as the major labeled fragmentation product, indicating that these cephalosporin-sensitive penicillin-binding proteins, for which no in vitro transpeptidase or carboxypeptidase activity has been found, catalyze the same fragmentation of the bound penicilloyl moiety previously described for several penicillin-sensitive D-alanine carboxypeptidases. PMID:115876

  19. A longitudinal field trial assesing the impact of feeding waste milk containing antibiotic residues on the prevalence of ESBL-producing Escherichia coli in calves.

    PubMed

    Brunton, L A; Reeves, H E; Snow, L C; Jones, J R

    2014-11-15

    A longitudinal field trial was carried out on a farm known to harbour cefotaximase (CTX-M)-positive Escherichia coli, in order to assess the impact of feeding waste milk containing antibiotic residues (WM+AR) on the prevalence of these bacteria in the faeces of calves. Fifty calves were alternately assigned to one of two groups at birth and fed either milk replacer (control group) or WM+AR (treatment group). Faecal samples were collected from all calves daily for the first week after enrolment, twice weekly until weaning, then weekly for a further six weeks. Environmental samples from the calf housing were collected weekly. WM+AR and powdered milk samples were examined for antibiotic residues and CTX-M-positive E. coli. Total E. coli and CTX-M-positive E. coli in faecal samples were enumerated using selective media. Regression analyses were performed on the bacterial count data using a population-averaged approach based on generalised estimating equations (GEE) to account for repeated measurements on individual calves over time. Cefquinome, a fourth generation cephalosporin, was detected in 87% of WM+AR samples at a mean concentration of 0.746 mg/l. All environmental sampling locations yielded CTX-M-positive E. coli. Significantly more pen floor samples were positive in the treatment group. Calves in the treatment group shed greater numbers of CTX-M-positive E. coli than calves in the control group throughout the study, and shedding decreased at a slower rate in the treatment group. CTX-M-positive E. coli persisted in a larger number of calves fed WM+AR compared with calves fed milk replacer where the prevalence in the treatment group declined significantly slower over time. There was no difference between calves fed WM+AR or calves fed milk replacer in the proportion of E. coli isolates that were CTX-M-positive. These findings indicate that feeding WM+AR increased the amount of resistant bacteria shed in the faeces. Shedding of CTX-M-positive E. coli persisted for longer in calves fed WM+AR, and persisted after weaning. PMID:25172121

  20. Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe

    PubMed Central

    de Kraker, Marlieke E. A.; Davey, Peter G.; Grundmann, Hajo

    2011-01-01

    Background The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS). Methods and Findings The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future. Conclusions Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern. Please see later in the article for the Editors' Summary PMID:22022233

  1. A computational model of antibiotic-resistance mechanisms in methicillin-resistant Staphylococcus aureus (MRSA).

    PubMed

    Murphy, James T; Walshe, Ray; Devocelle, Marc

    2008-09-21

    An agent-based model of bacteria-antibiotic interactions has been developed that incorporates the antibiotic-resistance mechanisms of Methicillin-Resistant Staphylococcus aureus (MRSA). The model, called the Micro-Gen Bacterial Simulator, uses information about the cell biology of bacteria to produce global information about population growth in different environmental conditions. It facilitates a detailed systems-level investigation of the dynamics involved in bacteria-antibiotic interactions and a means to relate this information to traditional high-level properties such as the Minimum Inhibitory Concentration (MIC) of an antibiotic. The two main resistance strategies against beta-lactam antibiotics employed by MRSA were incorporated into the model: beta-lactamase enzymes, which hydrolytically cleave antibiotic molecules, and penicillin-binding proteins (PBP2a) with reduced binding affinities for antibiotics. Initial tests with three common antibiotics (penicillin, ampicillin and cephalothin) indicate that the model can be used to generate quantitatively accurate predictions of MICs for antibiotics against different strains of MRSA from basic cellular and biochemical information. Furthermore, by varying key parameters in the model, the relative impact of different kinetic parameters associated with the two resistance mechanisms to beta-lactam antibiotics on cell survival in the presence of antibiotics was investigated. PMID:18577389

  2. A method for determining the free (unbound) concentration of ten beta-lactam antibiotics in human plasma using high performance liquid chromatography with ultraviolet detection.

    PubMed

    Briscoe, Scott E; McWhinney, Brett C; Lipman, Jeffrey; Roberts, Jason A; Ungerer, Jacobus P J

    2012-10-15

    With the clinical imperative to further research in the area of optimising antibiotic dosing in the intensive care setting, a simple high performance liquid chromatography method was developed and validated for routinely determining the free (unbound) concentration of ten beta-lactam antibiotics in 200 ?L of human plasma. Antibiotics determined include three cephalosporins (ceftriaxone, cephazolin and cephalotin); two carbapenems (meropenem and ertapenem); and five penicillins (ampicillin, piperacillin, benzylpenicillin, flucloxacillin and dicloxacillin). There was a single common sample preparation method involving ultracentrifugation and stabilisation. Chromatography was performed on a Waters XBridge C18 column with, depending on analytes, one of four acetonitrile-phosphate buffered mobile phases. Peaks of interest were detected via ultraviolet absorbance at 210, 260 and 304 nm. The method has been validated and used in a pathology laboratory for therapeutic drug monitoring in critically ill patients. The significant variability in the level of protein binding that is common with antibiotics traditionally considered to have high protein binding (e.g. ceftriaxone, cephazolin, ertapenem, flucloxacillin and dicloxacillin) suggests that this assay should be preferred for measuring the pharmacologically active concentration of beta-lactam antibiotics in a therapeutic drug monitoring programme. PMID:23026224

  3. Determination of endotoxin in injectable antibiotic preparations by the chromogenic assay method using a Limulus reagent (Tachypleus hemocyte lysate) and a chromogenic substrate.

    PubMed Central

    Yano, S; Hotta, Y; Takahashi, S

    1986-01-01

    The effects of 50 antibiotics on the detection and determination of bacterial endotoxins by the chromogenic method using a Limulus reagent (Tachypleus hemocyte lysate) and a chromogenic substrate of p-nitroaniline derivatives were tested, and the antibiotic concentration for 50% inhibition of the chromogenic reaction in the presence of 0.5 ng of endotoxin (Escherichia coli 0111:B4) per ml was estimated. All the antibiotic preparations were depyrogenized by ultrafiltration treatment before they were subjected to the test. The reaction was conducted in the presence of a high concentration (0.5 M) of Tris buffer to constantly maintain the pH of the reaction mixture, and liberated p-nitroaniline was determined by high-pressure liquid chromatography. Several aminoglycosides (amikacin, bekanamycin, kanamycin, and streptomycin sulfate), bleomycin hydrochloride, and fosfomycin disodium showed no inhibition of the reaction up to 20 mg/ml. However, other antibiotics, including penicillins, cephalosporins, macrolides, and tetracyclines, inhibited the reaction concentration dependently. Polymyxin B sulfate was the most potent inhibitor, with less than 8 micrograms/ml for 50% inhibition. It was concluded that the chromogenic method can be applied to the detection and determination of endotoxin in most of the antibiotic preparations. An application of this method to carbenicillin disodium preparations was exemplified. PMID:3700595

  4. Putrescine Reduces Antibiotic-Induced Oxidative Stress as a Mechanism of Modulation of Antibiotic Resistance in Burkholderia cenocepacia

    PubMed Central

    El-Halfawy, Omar M.

    2014-01-01

    Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic-resistant bacterium Burkholderia cenocepacia protects less-resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sublethal concentrations of PmB and other bactericidal antibiotics induces reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS, such as superoxide ion and hydrogen peroxide, was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild-type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sublethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine-synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study reveals BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections. PMID:24820075

  5. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    PubMed Central

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

    2013-01-01

    Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

  6. New valid spectrofluorimetric method for determination of selected cephalosporins in different pharmaceutical formulations using safranin as fluorophore

    NASA Astrophysics Data System (ADS)

    Derayea, Sayed M.; Ahmed, Hytham M.; Abdelmageed, Osama H.; Haredy, Ahmed M.

    2016-01-01

    A new validated spectrofluorimetric method has been developed for the determination of some cephalosporins namely; cefepime, cefaclor, cefadroxil, cefpodoxime and cefexime. The method was based on the reaction of these drugs with safranin in slightly alkaline medium (pH 8.0), to form ion-association complexes. The fluorescent products were extracted into chloroform and their fluorescence intensities were measured at 544-565 nm after excitation at 518-524 nm. The reaction conditions influencing the product formation and stability were investigated and optimized. The relative fluorescence intensity was proportional to the drug concentration in the linear ranges of 0.15-1.35, 0.35-1.25, 0.35-1.25, 0.20-1.44 and 0.20-1.25 μg/mL for cefepime, cefaclor, cefadroxil, cefpodoxime proxetil and cefexime, respectively. The detection limits were 40, 100, 100, 60 and 70 ng/mL, respectively. The performance of the developed method was evaluated in terms of Student's t-test and variance ratio F-test to find out the significance of proposed methods over the reference spectrophotometric method. Various pharmaceutical formulations were successfully analyzed using the proposed method and the results were in good agreement with those of the previously reported methods.

  7. Outer Membrane Profiles of Clonally Related Klebsiella pneumoniae Isolates from Clinical Samples and Activities of Cephalosporins and Carbapenems

    PubMed Central

    Ardanuy, Carmen; Liñares, Josefina; Domínguez, María Angeles; Hernández-Allés, Santiago; Benedí, Vicente J.; Martínez-Martínez, Luis

    1998-01-01

    Fifteen isolates of Klebsiella pneumoniae producing extended-spectrum β-lactamases (ESBLs) isolated during a nosocomial outbreak were studied. The strains belonged to the same clonal type, as shown by pulsed-field gel electrophoretic analysis of chromosomal DNA. All the isolates were resistant to extended-spectrum cephalosporins, aztreonam, gentamicin, and fluoroquinolones and were susceptible to carbapenems, tobramycin, netilmicin, and amikacin. None of the isolates expressed the OmpK36 porin. Eight isolates, for which the MICs of cefoxitin were ≥64 μg/ml, showed a diminished level or no expression of a 35-kDa porin. The MICs of meropenem, cefotaxime, and cefpirome were three to eight times higher for porin-deficient isolates than for isolates expressing the 35-kDa porin, but the MICs of imipenem increased two times for porin-deficient isolates compared to those for isolates expressing the porin. This MIC increase reverted to a level similar to that for the parental strain when porin-deficient isolates were transformed with the gene coding for the K. pneumoniae porin OmpK36. It is concluded that the high level of resistance to cefoxitin and the increase in the MICs of meropenem, cefotaxime, and cefpirome for the ESBL-producing K. pneumoniae isolates studied are associated with porin deficiency. PMID:9660996

  8. Acquisition of extended-spectrum cephalosporin- and colistin-resistant Salmonella enterica subsp. enterica serotype Newport by pilgrims during Hajj.

    PubMed

    Olaitan, Abiola Olumuyiwa; Dia, Ndye Mry; Gautret, Philippe; Benkouiten, Samir; Belhouchat, Khadidja; Drali, Tassadit; Parola, Philippe; Brouqui, Philippe; Memish, Ziad; Raoult, Didier; Rolain, Jean-Marc

    2015-06-01

    Gatherings like the Hajj involving many people who travel from different parts of the world represent a risk for the acquisition and dissemination of infectious diseases. In this study, acquisition of multidrug-resistant (MDR) Salmonella spp. in 2013 Hajj pilgrims from Marseille, France, was investigated. In total, 267 rectal swabs were collected from 129 participants before their departure and after their return from the pilgrimage as well as during the pilgrimage from patients with diarrhoea. Samples were screened for the presence of Salmonella using quantitative real-time PCR and culture. Whole-genome sequencing was performed to characterise one of the isolates, and the mechanism leading to colistin resistance was investigated. Six post-Hajj samples and one sample collected during a diarrhoea episode in Hajj were positive for Salmonella by real-time PCR, with five Salmonella enterica belonging to several serotypes recovered by culture, whereas no pre-Hajj sample was positive. Two of the isolates belonged to the epidemic Newport serotype, were resistant to cephalosporins, gentamicin and colistin, and harboured the bla(CTX-M-2) gene and a 12-nucleotide deletion in the pmrB gene leading to colistin resistance. This study shows that pilgrims acquired Salmonella bacteria, including a novel MDR clone, during the Hajj pilgrimage. This calls for more improved public health surveillance during Hajj because Salmonella is one of the most common diarrhoea-causing bacteria worldwide. Therefore, returning pilgrims could disseminate MDR bacteria worldwide upon returning to their home countries. PMID:25769786

  9. Antibiotic-resistant Klebsiella pneumoniae and Escherichia coli high-risk clones and an IncFII(k) mosaic plasmid hosting Tn1 (blaTEM-4) in isolates from 1990 to 2004.

    PubMed

    Rodríguez, Irene; Novais, Ângela; Lira, Felipe; Valverde, Aránzazu; Curião, Tânia; Martínez, José Luis; Baquero, Fernando; Cantón, Rafael; Coque, Teresa M

    2015-05-01

    We describe the genetic background of bla(TEM-4) and the complete sequence of pRYC11::bla(TEM-4), a mosaic plasmid that is highly similar to pKpQIL-like variants, predominant among TEM-4 producers in a Spanish hospital (1990 to 2004), which belong to Klebsiella pneumoniae and Escherichia coli high-risk clones responsible for the current spread of different antibiotic resistance genes. Predominant populations of plasmids and host adapted clonal lineages seem to have greatly contributed to the spread of resistance to extended-spectrum cephalosporins. PMID:25691645

  10. Antibiotic-Resistant Klebsiella pneumoniae and Escherichia coli High-Risk Clones and an IncFIIk Mosaic Plasmid Hosting Tn1 (blaTEM-4) in Isolates from 1990 to 2004

    PubMed Central

    Rodríguez, Irene; Novais, Ângela; Lira, Felipe; Valverde, Aránzazu; Curião, Tânia; Martínez, José Luis; Baquero, Fernando; Cantón, Rafael

    2015-01-01

    We describe the genetic background of blaTEM-4 and the complete sequence of pRYC11::blaTEM-4, a mosaic plasmid that is highly similar to pKpQIL-like variants, predominant among TEM-4 producers in a Spanish hospital (1990 to 2004), which belong to Klebsiella pneumoniae and Escherichia coli high-risk clones responsible for the current spread of different antibiotic resistance genes. Predominant populations of plasmids and host adapted clonal lineages seem to have greatly contributed to the spread of resistance to extended-spectrum cephalosporins. PMID:25691645

  11. Occurrences and fate of selected human antibiotics in influents and effluents of sewage treatment plant and effluent-receiving river Yamuna in Delhi (India).

    PubMed

    Mutiyar, Pravin K; Mittal, Atul K

    2014-01-01

    Antibiotics consumption has increased worldwide, and their residues are frequently reported in aquatic environments. It is believed that antibiotics reach aquatic water bodies through sewage. Medicine consumed for healthcare practices are often released into sewage, and after sewage treatment plant, it reaches the receiving water bodies of lakes or rivers. In the present study, we determined the fate of some commonly used antibiotics in a sewage treatment plant (STP) located in Delhi and the environmental concentration of these antibiotics in the Yamuna River, which receives the sewage and industrial effluent of Delhi. There are many reports on antibiotics occurrences in STP and river water worldwide, but monitoring data from the Indian subcontinent is sparse. Samples were taken from a STP and from six sampling sites on the Yamuna River. Several antibiotics were tested for using offline solid-phase extraction followed by high-performance liquid chromatography equipped with photodiode array analysis. Recoveries varied from 25.5-108.8 %. Ampicillin had the maximum concentration in wastewater influents (104.2 ± 98.11 μg l(-1)) and effluents (12.68 ± 8.38 μg l(-1)). The fluoroquinolones and cephalosporins had the lower concentrations. Treatment efficiencies varied between 55 and 99 %. Significant amounts of antibiotics were discharged in effluents and were detected in the receiving water body. The concentration of antibiotics in the Yamuna River varied from not detected to 13.75 μg l(-1) (ampicillin) for the compounds investigated. PMID:24085621

  12. Validation of a microbiological method: the STAR protocol, a five-plate test, for the screening of antibiotic residues in milk.

    PubMed

    Gaudin, V; Maris, P; Fuselier, R; Ribouchon, J-L; Cadieu, N; Rault, A

    2004-05-01

    The results of an in-house laboratory validation of a microbiological method for the screening of antibiotic residues in milk are presented. The sensitivity of this five-plate test, called Screening Test for Antibiotic Residues (STAR), was established by the analysis of milk samples spiked with 66 antibiotics at eight different concentrations. Ten different groups of antibiotics were studied: macrolides, aminoglycosides, cephalosporins, penicillins, quinolones, tetracyclines, sulphonamides, lincosamides, phenicolated and miscellaneous drugs. It was shown that 21 antibiotics were detected by the STAR protocol at or below the maximum residue limit (MRL), and that a further 27 drugs could be detected at levels from the MRL up to four times the MRL. The sensitivity of the STAR protocol was at or below the MRL for three macrolides, one tetracycline, two aminoglycosides, some sulphonamides, half of the beta-lactams, quinolones, lincosamides, trimethoprim and baquiloprim. Moreover, the STAR protocol was at least twice as sensitive as conventional methods for macrolides, quinolones and tetracyclines. The other antibiotics had limits of detection between four and 150 times the MRL. Each plate was preferentially sensitive for one or two families of antibacterials: the plate Bacillus cereus for tetracyclines, the plate Escherichia coli for quinolones, the plate Basillus subtilis for aminoglycosides, the plate Kocuria varians for macrolides, and the plate Bacillus stearothermophilus for sulphonamides and beta-lactams. This method has been used routinely on a day-to-day basis to direct the physicochemical confirmation towards one or two families of antibiotics. Considering the high cost of liquid chromatography coupled with tandem mass spectrometry detection analyses, the reduction of the range of antibiotics to test for confirmation is a significant gain in time and money. PMID:15204543

  13. [Strategies to avoid antibiotic resistance].

    PubMed

    Kees, M G

    2013-03-01

    Antibiotics are used very frequently in critically ill patients as a causal and often life-saving treatment; however, the high density of use of broad spectrum antibiotics contributes to a further deterioration in resistance trends, which makes a rational prescription behavior mandatory. This particularly includes measures which lead to the reduction of antibiotic use, i.e. rigorous indications, targeted de-escalation and limited duration. For optimal efficacy of a necessary treatment the integration of pharmacokinetic and pharmacodynamic principles can be helpful. PMID:23344520

  14. Antibiotic Treatment of Hidradenitis Suppurativa.

    PubMed

    Bettoli, Vincenzo; Join-Lambert, Olivier; Nassif, Aude

    2016-01-01

    Although hidradenitis suppurativa (HS) is not primarily an infectious disease, antibiotics are widely used to treat HS. Recent microbiological data show that HS suppurating lesions are associated with a polymorphous anaerobic flora, including actinomycetes and milleri group streptococci, and can therefore be considered as polymicrobial soft tissue and skin infections. Analysis of the literature provides little information on the efficacy of antibiotics in HS but suggests a beneficial effect of certain antimicrobial treatments, depending on the clinical severity of the disease. Patients must be informed and should agree with the treatment strategy before starting antibiotic treatments. PMID:26617361

  15. Antibiotic resistance in wild birds

    PubMed Central

    Bonnedahl, Jonas

    2014-01-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

  16. Systemic antibiotic therapy in periodontics

    PubMed Central

    Kapoor, Anoop; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak

    2012-01-01

    Systemic antibiotics in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy. PMID:23559912

  17. [Production of hydrolases by lactic acid bacteria and bifidobacteria and their antibiotic resistance].

    PubMed

    Novik, G I; Astanovich, N I; Riabaia, N E

    2007-01-01

    It was demonstrated that bifidobacteria and lactic acid bacteria B. adolescentis and Lactobacillus sp. synthesized extracellular enzymes cleaving glycoside bonds in the molecules of dextran, pectic acid, and soluble starch. The maximal production of extracellular beta-galactosidase by B. adolescentis 91-BIM and 94-BIM at a rate of 0.08 and 0.03 U/mg h was observed during the exponential growth phase at 5 and 12 h of cultivation, respectively. The cultures of bifidobacteria retained 60-70% of beta-galactosidase and alpha-amylase activities after six months of storage. The bifidobacterium strains studied were resistant to amphotericin and aminoglycosides (gentamicin, kanamycin, and netromycin). The lactam antibiotics (ampicillin, benzylpenicillin, bicillin 3, bicillin 5, and carbenicillin), the preparations inhibiting protein synthesis at the level of ribosomes (lincomycin), RNA polymerase inhibitors (rifampin), cephalosporin, and Maxipime inhibited the growth of bifidobacteria. Rifampin, erythromycin, amphotericin, Maxipime, Fortum, doxycycline, levomycetin, streptomycin, and the aminoglycosides netromycin, gentamicin, and kanamycin did not have an effect on the growth of Lactobacillus sp., whereas semisynthetic derivatives of penicillin, carbenicillin and ampicillin, inhibited its growth as well as Oxamp and lincomycin. The lactam antibiotics benzylpenicillin, bicillin 3, and bicillin 5 inhibited the growth of lactic acid bacilli by 30-90%. PMID:17476804

  18. In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.

    PubMed

    Clendennen, T E; Hames, C S; Kees, E S; Price, F C; Rueppel, W J; Andrada, A B; Espinosa, G E; Kabrerra, G; Wignall, F S

    1992-02-01

    Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines. PMID:1605592

  19. Effect on the human normal microflora of oral antibiotics for treatment of urinary tract infections.

    PubMed

    Edlund, C; Nord, C E

    2000-09-01

    Oral administration of antibiotics for treatment of urinary tract infections (UTIs) can cause ecological disturbances in the normal intestinal microflora. Poorly absorbed drugs can reach the colon in active form, suppress susceptible microorganisms and disturb the ecological balance. Suppression of the normal microflora may lead to reduced colonization resistance with subsequent overgrowth of pre-existing, naturally resistant microorganisms, such as yeasts and Clostridium difficile. New colonization by resistant potential pathogens may also occur and may spread within the body or to other patients and cause severe infections. It is therefore important to learn more about the ecological effects of antibacterial agents on the human microflora. The impact on intestinal microorganisms of oral antibiotics used for the treatment of UTIs is reviewed here. Ampicillin, amoxycillin and co-amoxiclav suppress both the aerobic and anaerobic intestinal microflora with overgrowth of ampicillin-resistant Enterobacteriaceae. Pivmecillinam also affects the intestinal microflora, suppressing Escherichia coli, but does not have a major effect on the anaerobic microflora. Several orally administered cephalosporins, such as cefixime, cefpodoxime, cefprozil and ceftibuten, reduce the number of Enterobacteriaceae and increase the number of enterococci. Colonization with C. difficile has also been observed. Fluoroquinolones eliminate or strongly suppress intestinal Enterobacteriaceae, but affect enterococci and anaerobic bacteria only slightly. When antimicrobial agents are prescribed for the treatment of UTIs, not only the antimicrobial spectrum of the agent but also the potential ecological disturbances, including the risk of emergence of resistant strains, should be considered. PMID:11051623

  20. Effect on the human normal microflora of oral antibiotics for treatment of urinary tract infections.

    PubMed

    Edlund; Nord

    2000-08-01

    Oral administration of antibiotics for treatment of urinary tract infections (UTIs) can cause ecological disturbances in the normal intestinal microflora. Poorly absorbed drugs can reach the colon in active form, suppress susceptible microorganisms and disturb the ecological balance. Suppression of the normal microflora may lead to reduced colonization resistance with subsequent overgrowth of pre-existing, naturally resistant microorganisms, such as yeasts and Clostridium difficile. New colonization by resistant potential pathogens may also occur and may spread within the body or to other patients and cause severe infections. It is therefore important to learn more about the ecological effects of antibacterial agents on the human microflora. The impact on intestinal microorganisms of oral antibiotics used for the treatment of UTIs is reviewed here. Ampicillin, amoxycillin and co-amoxiclav suppress both the aerobic and anaerobic intestinal microflora with overgrowth of ampicillin-resistant Enterobacteriaceae. Pivmecillinam also affects the intestinal microflora, suppressing Escherichia coli, but does not have a major effect on the anaerobic microflora. Several orally administered cephalosporins, such as cefixime, cefpodoxime, cefprozil and ceftibuten, reduce the number of Enterobacteriaceae and increase the number of enterococci. Colonization with C. difficile has also been observed. Fluoroquinolones eliminate or strongly suppress intestinal Enterobacteriaceae, but affect enterococci and anaerobic bacteria only slightly. When antimicrobial agents are prescribed for the treatment of UTIs, not only the antimicrobial spectrum of the agent but also the potential ecological disturbances, including the risk of emergence of resistant strains, should be considered. PMID:10969051

  1. [Resistance to "last resort" antibiotics in Gram-positive cocci: The post-vancomycin era].

    PubMed

    Rincn, Sandra; Panesso, Diana; Daz, Lorena; Carvajal, Lina P; Reyes, Jinnethe; Munita, Jos M; Arias, Csar A

    2014-04-01

    New therapeutic alternatives have been developed in the last years for the treatment of multidrug-resistant Gram-positive infections. Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are considered a therapeutic challenge due to failures and lack of reliable antimicrobial options. Despite concerns related to the use of vancomycin in the treatment of severe MRSA infections in specific clinical scenarios, there is a paucity of solid clinical evidence that support the use of alternative agents (when compared to vancomycin). Linezolid, daptomycin and tigecycline are antibiotics approved in the last decade and newer cephalosporins (such as ceftaroline and ceftobiprole) and novel glycopeptides (dalvavancin, telavancin and oritavancin) have reached clinical approval or are in the late stages of clinical development. This review focuses on discussing these newer antibiotics used in the "post-vancomycin" era with emphasis on relevant chemical characteristics, spectrum of antimicrobial activity, mechanisms of action and resistance, as well as their clinical utility. PMID:24968051

  2. Ferrate(VI) oxidation of ?-lactam antibiotics: reaction kinetics, antibacterial activity changes, and transformation products.

    PubMed

    Karlesa, Anggita; De Vera, Glen Andrew D; Dodd, Michael C; Park, Jihye; Espino, Maria Pythias B; Lee, Yunho

    2014-09-01

    Oxidation of ?-lactam antibiotics by aqueous ferrate(VI) was investigated to determine reaction kinetics, reaction sites, antibacterial activity changes, and transformation products. Apparent second-order rate constants (kapp) were determined in the pH range 6.0-9.5 for the reaction of ferrate(VI) with penicillins (amoxicillin, ampicillin, cloxacillin, and penicillin G), a cephalosporin (cephalexin), and several model compounds. Ferrate(VI) shows an appreciable reactivity toward the selected ?-lactams (kapp for pH 7 = 110-770 M(-1) s(-1)). The pH-dependent kapp could be well explained by considering species-specific reactions between ferrate(VI) and the ?-lactams (with reactions occurring at thioether, amine, and/or phenol groups). On the basis of the kinetic results, the thioether is the main reaction site for cloxacillin and penicillin G. In addition to the thioether, the amine is a reaction site for ampicillin and cephalexin, and amine and phenol are reaction sites for amoxicillin. HPLC/MS analysis showed that the thioether of ?-lactams was transformed to stereoisomeric (R)- and (S)-sulfoxides and then to a sulfone. Quantitative microbiological assay of ferrate(VI)-treated ?-lactam solutions indicated that transformation products resulting from the oxidation of cephalexin exhibited diminished, but non-negligible residual activity (i.e., ?24% as potent as the parent compound). For the other ?-lactams, the transformation products showed much lower (<5%) antibacterial potencies compared to the parent compounds. Overall, ferrate(VI) oxidation appears to be effective as a means of lowering the antibacterial activities of ?-lactams, although alternative approaches may be necessary to achieve complete elimination of cephalosporin activities. PMID:25073066

  3. Genome sequencing of a Neisseria gonorrhoeae isolate of a successful international clone with decreased susceptibility and resistance to extended-spectrum cephalosporins.

    PubMed

    Hess, David; Wu, Abel; Golparian, Daniel; Esmaili, Sarah; Pandori, Will; Sena, Emilee; Klausner, Jeffrey D; Barry, Pennan; Unemo, Magnus; Pandori, Mark

    2012-11-01

    The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150 coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient. PMID:22908152

  4. Genome Sequencing of a Neisseria gonorrhoeae Isolate of a Successful International Clone with Decreased Susceptibility and Resistance to Extended-Spectrum Cephalosporins

    PubMed Central

    Wu, Abel; Golparian, Daniel; Esmaili, Sarah; Pandori, Will; Sena, Emilee; Klausner, Jeffrey D.; Barry, Pennan; Unemo, Magnus; Pandori, Mark

    2012-01-01

    The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150 coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient. PMID:22908152

  5. Multiscale Models of Antibiotic Probiotics

    PubMed Central

    Kaznessis, Yiannis N.

    2014-01-01

    The discovery of antibiotics is one of the most important advances in the history of humankind. For eighty years human life expectancy and standards of living improved greatly thanks to antibiotics. But bacteria have been fighting back, developing resistance to our most potent molecules. New, alternative strategies must be explored as antibiotic therapies become obsolete because of bacterial resistance. Mathematical models and simulations guide the development of complex technologies, such as aircrafts, bridges, communication systems and transportation systems. Herein, models are discussed that guide the development of new antibiotic technologies. These models span multiple molecular and cellular scales, and facilitate the development of a technology that addresses a significant societal challenge. We argue that simulations can be a creative source of knowledge. PMID:25313349

  6. Antibiotic Resistance Questions and Answers

    MedlinePLUS

    ... has been called one of the world's most pressing public health problems. Antibiotic resistance can cause illnesses ... resistant through mutation of their genetic material. The Food and Drug Administration's (FDA's) Center for Veterinary Medicine ( ...

  7. Resistance-induced antibiotic substitution.

    PubMed

    Howard, David H

    2004-06-01

    In many cases, physicians prescribe antibiotics without knowing whether an individual patient is infected with a susceptible or resistant pathogen. As the proportion of resistant organisms in a community increases, physicians substitute away from older-inexpensive drugs to newer, more expensive agents as first line therapy. This paper explores the implications of resistance-induced antibiotic substitution for epidemiological models to predict future resistance levels, efforts to measure the health care costs associated with resistance, and policies to improve physicians' antibiotic prescribing decisions. The extent of resistance-induced substitution in outpatient settings is documented using a data set consisting of observations on initial physician office visits for otitis media in the US controlling for new product introductions and price increases, per prescription antibiotic spending increased by 22% between 1980 and 1996, corresponding to a steep increase in resistance levels over the same period. PMID:15185388

  8. The Double Life of Antibiotics

    PubMed Central

    Yap, Mee-Ngan F.

    2013-01-01

    Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response. The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant.~Alexander Fleming PMID:24003650

  9. β-Lactam Antibiotics Renaissance

    PubMed Central

    Qin, Wenling; Panunzio, Mauro; Biondi, Stefano

    2014-01-01

    Since the 1940s β-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of β-lactam resistance has reached the point where many marketed β-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel β-lactam antibiotics and β-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel β-lactam antibiotics and β-lactamase inhibitors.

  10. Heat inactivation of beta-lactam antibiotics in milk.

    PubMed

    Zorraquino, M A; Roca, M; Fernandez, N; Molina, M P; Althaus, R

    2008-06-01

    The presence of residues of antimicrobial substances in milk is one of the main concerns of the milk industry, as it poses a risk of toxicity to public health, and can seriously influence the technological properties of milk and dairy products. Moreover, the information available on the thermostability characteristics of these residues, particularly regarding the heat treatments used in control laboratories and the dairy industry, is very scarce. The aim of the study was, therefore, to analyze the effect of different heat treatments (40 degrees C for 10 min, 60 degrees C for 30 min, 83 degrees C for 10 min, 120 degrees C for 20 min, and 140 degrees C for 10 s) on milk samples fortified with three concentrations of nine beta-lactam antibiotics (penicillin G: 3, 6, and 12 microg/liter; ampicillin: 4, 8, and 16 microg/liter; amoxicillin: 4, 8, and 16 microg/liter; cloxacillin: 60, 120, and 240 microg/liter; cefoperazone: 55, 110, and 220 microg/liter; cefquinome: 100, 200, and 400 microg/liter; cefuroxime: 65, 130, and 260 microg/liter; cephalexin: 80, 160, and 220 microg/ liter; and cephalonium: 15, 30, and 60 microg/liter). The method used was a bioassay based on the inhibition of Geobacillus stearothermophilus var. calidolactis. The results showed that heating milk samples at 40 degrees C for 10 min hardly produced any heat inactivation at all, while the treatment at 83 degrees C for 10 min caused a 20% loss in penicillin G, 27% in cephalexin, and 35% in cefuroxime. Of the three dairy industry heat treatments studied in this work, low pasteurization (60 degrees C for 30 min) and treatment at 140 degrees C for 10 s only caused a small loss of antimicrobial activity, whereas classic sterilization (120 degrees C for 20 min) showed a high level of heat inactivation of over 65% for penicillins and 90% for cephalosporins. PMID:18592745

  11. Diverse Antibiotic Resistance Genes in Dairy Cow Manure

    PubMed Central

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-01-01

    ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

  12. Potential impacts of aquatic pollutants: sub-clinical antibiotic concentrations induce genome changes and promote antibiotic resistance

    PubMed Central

    Chow, Louise; Waldron, Liette; Gillings, Michael R.

    2015-01-01

    Antibiotics are disseminated into aquatic environments via human waste streams and agricultural run-off. Here they can persist at low, but biologically relevant, concentrations. Antibiotic pollution establishes a selection gradient for resistance and may also raise the frequency of events that generate resistance: point mutations; recombination; and lateral gene transfer. This study examined the response of bacteria to sub-inhibitory levels of antibiotics. Pseudomonas aeruginosa and Pseudomonas protegens were exposed kanamycin, tetracycline or ciprofloxacin at 1/10 the minimal inhibitory concentration (MIC) in a serial streaking experiment over 40 passages. Significant changes in rep-PCR fingerprints were noted in both species when exposed to sub-inhibitory antibiotic concentrations. These changes were observed in as few as five passages, despite the fact that the protocols used sample less than 0.3% of the genome, in turn suggesting much more widespread alterations to sequence and genome architecture. Experimental lines also displayed variant colony morphologies. The final MICs were significantly higher in some experimental lineages of P. protegens, suggesting that 1/10 the MIC induces de-novo mutation events that generate resistance phenotypes. The implications of these results are clear: exposure of the environmental microbiome to antibiotic pollution will induce similar changes, including generating newly resistant species that may be of significant concern for human health. PMID:26300869

  13. Antibiotics in third molar surgery.

    PubMed

    Vlcek, Daniel; Razavi, Amir; Kuttenberger, Johannes J

    2014-01-01

    The aim of this survey was to assess the knowledge and practice of Swiss dentists focusing on the use of antibiotics in prophylactic surgical removal of lower wisdom teeth. A postal survey was conducted among all 3288 dentists who are members of the Swiss Dental Society (SSO) representing nearly all dentists in Switzerland. The questionnaire consisted of 13 questions with mostly multiple-choice answers. Demographic profile, surgical experience, the use of antibiotics, and wound management, i.e. wound closure and the use of mouth rinse were assessed. A response rate of 55% was obtained. Most Swiss dentists perform surgical extractions in their practices. Of all dentists, 18.6% used antibiotics routinely, but a large variation was found comparing the three linguistic regions of Switzerland with the highest prescription rate of 48% in the French-speaking south-west of Switzerland. Fifty-two percent of dentists prescribed amoxicillin in a dose of 750 mg. Most often three daily doses were prescribed (47%). A postoperative regime was prescribed by 54.4% of dentists. French language (p=0.003), graduation from the university of Geneva (p=0.007), foreign diplomas (p<0.001), and dentists with diplomas awarded from 2001-2006 (p=0.004) showed a highly significant correlation with the use of antibiotics. In Switzerland, prophylactic antibiotics are used in third molar surgery. Antibiotic prescription however largely depends on geographical situation and dentist profiles. The assessment of antibiotic use in private practices is important in the light of growing evidence that antibiotic overuse may lead to development of multiresistant bacterial strains. In a second part results regarding wound management and mouth rinse will be presented. PMID:24671748

  14. The determinants of the antibiotic resistance process

    PubMed Central

    Franco, Beatriz Espinosa; Altagracia Martnez, Marina; Snchez Rodrguez, Martha A; Wertheimer, Albert I

    2009-01-01

    Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words determinants, antibiotic, and antibiotic resistance to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

  15. Assessing the combined effects from two kinds of cephalosporins on green alga (Chlorella pyrenoidosa) based on response surface methodology.

    PubMed

    Guo, Ruixin; Xie, Weishu; Chen, Jianqiu

    2015-04-01

    The present work evaluated the combined effects of cefradine and ceftazidime on the green alga Chlorella pyrenoidosa using response surface methodologies (RSM). After a 48 h-exposure, the population growth rate (PGR), the chlorophyll-a content and the SOD content of the alga increased with increased concentrations of two antibiotics. However, the three responses did not continue to demonstrate significant increases once antibiotic concentrations exceed a moderate level. Three two order polynomial regression equations were obtained to describe well the relationship between the responses of the alga and the two antibiotics' concentration (R(2) = 0.9997, 0.9292 and 0.9039, respectively). Three 3 D-surface graphs and their contour plots showed directly the changing trends of the alga under the combined effects of two antibiotics. This study for the first time employed the RSM in ecotoxicology, which indicated that the RSM should be placed under a feasible and a potential application prospect in toxicity assessment. PMID:25684417

  16. Parallel Mapping of Antibiotic Resistance Alleles in Escherichia coli.

    PubMed

    Weiss, Sophie J; Mansell, Thomas J; Mortazavi, Pooneh; Knight, Rob; Gill, Ryan T

    2016-01-01

    Chemical genomics expands our understanding of microbial tolerance to inhibitory chemicals, but its scope is often limited by the throughput of genome-scale library construction and genotype-phenotype mapping. Here we report a method for rapid, parallel, and deep characterization of the response to antibiotics in Escherichia coli using a barcoded genome-scale library, next-generation sequencing, and streamlined bioinformatics software. The method provides quantitative growth data (over 200,000 measurements) and identifies contributing antimicrobial resistance and susceptibility alleles. Using multivariate analysis, we also find that subtle differences in the population responses resonate across multiple levels of functional hierarchy. Finally, we use machine learning to identify a unique allelic and proteomic fingerprint for each antibiotic. The method can be broadly applied to tolerance for any chemical from toxic metabolites to next-generation biofuels and antibiotics. PMID:26771672

  17. Parallel Mapping of Antibiotic Resistance Alleles in Escherichia coli

    PubMed Central

    Mortazavi, Pooneh; Knight, Rob; Gill, Ryan T.

    2016-01-01

    Chemical genomics expands our understanding of microbial tolerance to inhibitory chemicals, but its scope is often limited by the throughput of genome-scale library construction and genotype-phenotype mapping. Here we report a method for rapid, parallel, and deep characterization of the response to antibiotics in Escherichia coli using a barcoded genome-scale library, next-generation sequencing, and streamlined bioinformatics software. The method provides quantitative growth data (over 200,000 measurements) and identifies contributing antimicrobial resistance and susceptibility alleles. Using multivariate analysis, we also find that subtle differences in the population responses resonate across multiple levels of functional hierarchy. Finally, we use machine learning to identify a unique allelic and proteomic fingerprint for each antibiotic. The method can be broadly applied to tolerance for any chemical from toxic metabolites to next-generation biofuels and antibiotics. PMID:26771672

  18. [Changes in antibiotic resistance of Pseudomonas aeruginosa isolates over the past 11 years in Turkey: a meta-analysis].

    PubMed

    Aykan, ?adiye Berna; iftci, ?hsan Hakk?

    2015-07-01

    The increased antibiotic resistance and diversity of resistance mechanisms in clinical isolates of Pseudomonas aeruginosa lead to serious problems in treatment. Bacterial resistance against antibiotics can be influenced by patient characteristics, antibiotic usage policy depending on the country, region, hospital, clinics and even may vary during treatment. In this meta-analysis study, we aimed to evaluate the trends in P.aeruginosa antibiotic resistance over the past 11 years. The study was planned and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the literature search method, criteria for inclusion and exclusion, evaluation of publications, data collection, and statistical analysis were performed. To identify relevant publications, two national databases (ULAKBIM and TURK MEDLINE) and one international database (PubMed) were searched. Published manuscripts were evaluated for exclusion criteria, after the study data were collected, and statistical analyses were performed. The data obtained from the literature were assessed under a common unit. The calculations made in the 95% confidence interval value of p?0.05 was considered statistically significant. As a result of exclusion criteria, meta-analysis was performed for 48 studies published between 2003 and 2013. For the evaluation of the changes in antibiotic resistance of P.aeruginosa isolates over time, studies were divided into three groups according to the year of publication. The number of publications was relatively consistent over the course of the study period with 17 studies published in 2003-2006; 14 in 2007-2009, and 17 in 2010-2013. There were significant changes in antibiotic resistance results within years however, none of these differences were statistically significant (p>0.05). Carbapenem resistance, especially imipenem resistance, increased between 2007 and 2009, however, the changes were not statistically significant for either imipenem or meropenem (p=0.254, p=0.499, respectively). Through the 11-year period, the resistance rates for imipenem and meropenem were 29.4% and 32.1%, respectively. In the last 4 years of the study period, notable decrease were reported in antibiotic groups except for cefepime from cephalosporins and monobactam; the resistance rates for cephalosporins remained unchanged during this time period. The reported resistance rates for cefepime and ceftazidime were 41.4% and 43.9%, respectively. Similar decreases in resistance to aminoglycoside antibiotics, including amikacin, gentamicin, netilmicin, and tobramycin, were also seen, however, these changes were not statistically significant (p>0.05). The current data suggested that antibiotic resistance in P.aeruginosa has a tendency to decrease in our country. Though being at the bottom of the ladder, it can be expressed that rational and restricted use of antibiotics policy, contributed to the strength of the decrease; however for the decline of resistance to a reasonable level, new and sustainable policy is necessary to be implemented. PMID:26313277

  19. MULTIRESIDUE DETERMINATION OF FLUOROQUINOLONE ANTIBIOTICS IN EGGS USING LIQUID CHROMATOGRAPHY-FLUORESCENCE-MASS SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluoroquinolone antibiotics are currently used in both medical and veterinary applications. Use of these antibiotics in food animals has generated concern as the presence of these residues in food may contribute to increased microbial resistance in humans. Effective methods for analysis of fluoroq...

  20. Clonally related Neisseria gonorrhoeae isolates with decreased susceptibility to the extended-spectrum cephalosporin cefotaxime in Amsterdam, the Netherlands.

    PubMed

    Heymans, Raymond; Bruisten, Sylvia M; Golparian, Daniel; Unemo, Magnus; de Vries, Henry J C; van Dam, Alje P

    2012-03-01

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 ?g/ml (group A), 54 with a cefotaxime MIC of 0.125 ?g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 ?g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial. PMID:22214779

  1. Clonally Related Neisseria gonorrhoeae Isolates with Decreased Susceptibility to the Extended-Spectrum Cephalosporin Cefotaxime in Amsterdam, the Netherlands

    PubMed Central

    Heymans, Raymond; Bruisten, Sylvia M.; Golparian, Daniel; Unemo, Magnus; de Vries, Henry J. C.

    2012-01-01

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 μg/ml (group A), 54 with a cefotaxime MIC of 0.125 μg/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 μg/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial. PMID:22214779

  2. Comparison of broad-spectrum cephalosporin-resistant Escherichia coli isolated from dogs and humans in Hokkaido, Japan.

    PubMed

    Okubo, Torahiko; Sato, Toyotaka; Yokota, Shin-ichi; Usui, Masaru; Tamura, Yutaka

    2014-04-01

    Resistance to broad-spectrum cephalosporins (BSCs) in Enterobacteriaceae in companion animals has become a great concern for public health. To estimate the dissemination of BSC-resistant bacteria between dog and human, we examined the BSC-resistance determinants of and genetic similarities between 69 BSC-resistant Escherichia coli isolates derived from canine rectal swabs (n=28) and human clinical samples (n=41). Some E.coli isolates possessed blaTEM-1b (14 canine and 16 human isolates), blaCTx-M-2 (6 human isolates), blaCTx-M-14 (3 canine and 14 human isolates), blaCTx-M-27 (1 canine and 15 human isolates), and blaCMY-2 (11 canine and 3 human isolates). The possession of CTX-M-type ?-lactamases was significantly more frequent in human isolates, whereas CMY-2 was more common in canine isolates. Bacterial typing methods (phylogenetic typing, O-antigen serotyping, and pulsed-field gel electrophoresis) showed little clonal relationship between canine isolates and human isolates. Plasmid analysis and Southern blotting indicated that the plasmids encoding CMY-2 were similar among canine and human isolates. Based on the differences in the major ?-lactamase and the divergence of bacterial types between canine and human isolates, it seems that clonal dissemination of BSC-resistant E.coli between canines and humans is limited. The similarity of the CMY-2-encoding plasmid suggests that plasmid-mediated ?-lactamase gene transmission plays a role in interspecies diffusion of BSC-resistant E.coli between dog and human. PMID:24709044

  3. Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of Enterococcus faecium from the Intestinal Epithelium

    PubMed Central

    Top, Janetta; Bayjanov, Jumamurat R.; Kemperman, Hans; Rogers, Malbert R. C.; Paganelli, Fernanda L.; Bonten, Marc J. M.; Willems, Rob J. L.

    2015-01-01

    ABSTRACT The microbiota of the mammalian gastrointestinal tract is a complex ecosystem of bacterial communities that continuously interact with the mucosal immune system. In a healthy host, the mucosal immune system maintains homeostasis in the intestine and prevents invasion of pathogenic bacteria, a phenomenon termed colonization resistance. Antibiotics create dysbiosis of microbiota, thereby decreasing colonization resistance and facilitating infections caused by antibiotic-resistant bacteria. Here we describe how cephalosporin antibiotics create dysbiosis in the mouse large intestine, allowing intestinal outgrowth of antimicrobial-resistant Enterococcus faecium. This is accompanied by a reduction of the mucus-associated gut microbiota layer, colon wall, and Muc-2 mucus layer. E. faecium agglutinates intraluminally in an extracellular matrix consisting of secretory IgA (sIgA), polymeric immunoglobulin receptor (pIgR), and epithelial cadherin (E-cadherin) proteins, thereby maintaining spatial segregation of E. faecium from the intestinal wall. Addition of recombinant E-cadherin and pIgR proteins or purified IgA to enterococci in vitro mimics agglutination of E. faecium in vivo. Also, the Ca2+ levels temporarily increased by 75% in feces of antibiotic-treated mice, which led to deformation of E-cadherin adherens junctions between colonic intestinal epithelial cells and release of E-cadherin as an extracellular matrix entrapping E. faecium. These findings indicate that during antibiotic-induced dysbiosis, the intestinal epithelium stays separated from an invading pathogen through an extracellular matrix in which sIgA, pIgR, and E-cadherin are colocalized. Future mucosal vaccination strategies to control E. faecium or other opportunistic pathogens may prevent multidrug-resistant infections, hospital transmission, and outbreaks. PMID:26556272

  4. Prolonged antibiotic use induces intestinal injury in mice that is repaired after removing antibiotic pressure: implications for empiric antibiotic therapy

    PubMed Central

    Romick-Rosendale, Lindsey E.; Legomarcino, Anne; Patel, Neil B.; Morrow, Ardythe L.

    2015-01-01

    Metabolic profiling of urine and fecal extracts, histological investigation of intestinal ilea, and fecal metagenomics analyses were used to investigate effects of prolonged antibiotic use in mice. The study provides insight into the effects of extended empiric antibiotic therapy in humans. Mice were administered a broad-spectrum antibiotic for four consecutive days followed by oral gavage with Clostridium butyricum, an opportunistic gram-positive pathogenic bacteria commonly isolated in fecal and blood cultures of necrotizing enterocolitis patients. Metagenomics data indicated loss of bacterial diversity after 4 days on antibiotics that was restored after removing antibiotic pressure. Histological analyses indicated damage to ileal villi after antibiotic treatment that underwent repair after lifting antibiotic pressure. Metabolic profiling confirmed intestinal injury in antibiotic-treated mice indicated by increased urinary trans-4-hydroxy-l-proline, a breakdown product of collagen present in connective tissue of ileal villi that may serve as a biomarker for antibiotic-induced injury in at risk populations. PMID:26273236

  5. Organic or antibiotic-free labeling does not impact the recovery of enteric pathogens and antimicrobial-resistant Escherichia coli from fresh retail chicken.

    PubMed

    Mollenkopf, Dixie F; Cenera, Johana K; Bryant, Erin M; King, Christy A; Kashoma, Isaac; Kumar, Anand; Funk, Julie A; Rajashekara, Gireesh; Wittum, Thomas E

    2014-12-01

    We investigated the implied health benefits of retail chicken breast labeled as "organic" or "antibiotic-free" when compared to conventional products based on frequency of contamination by Salmonella spp., Campylobacter spp., and coliform bacteria resistant to fluoroquinolones, extended-spectrum cephalosporins, or carbapenems. We purchased 231 prepackaged chicken breasts from 99 grocery stores representing 17 retail chains in Ohio, Michigan, and Pennsylvania from June to September 2012. Ninety-six (41.5%) packages were labeled "antibiotic free" and 40 (17.3%) were labeled "organic," with the remaining 95 (41.1%) making neither label claim. Salmonella were recovered from 56 (24.2%) packages, and the recovery rate was not different between product types. Five percent of packages contained Salmonella carrying the extended-spectrum cephalosporin resistance gene bla(CMY-2), representing 21.4% of Salmonella isolates. Campylobacter spp. were recovered from 10.8% of packages, with observed recovery rates similar for the three product types. Using selective media, we recovered Escherichia coli harboring bla(CMY-2) from over half (53.7%) of packages, with similar recovery rates for all product types. In addition, we recovered E. coli carrying bla(CTX-M) from 6.9% of packages, and E. coli with QRDR mutations from 8.2% of packages. Fluoroquinolone-resistant E. coli recovered using selective media were more common (p<0.05) in conventional (18.9%) compared to organic (0) and antibiotic-free (2.1%) packages. Our results indicate that, regardless of product type, fresh retail chicken breast is commonly contaminated with enteric pathogens associated with foodborne illness and commensal bacteria harboring genes conferring resistance to critically important antimicrobial drugs. PMID:25405393

  6. WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics

    PubMed Central

    2012-01-01

    Summary Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians. PMID:22958542

  7. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    EPA Science Inventory

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  8. Background antibiotic resistance patterns in antibiotic-free pastured poultry production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

  9. Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study.

    PubMed

    Erdem, Hakan; Ulu-Kilic, Aysegl; Kilic, Selim; Karahocagil, Mustafa; Shehata, Ghaydaa; Eren-Tulek, Necla; Yetkin, Funda; Celen, Mustafa Kemal; Ceran, Nurgul; Gul, Hanefi Cem; Mert, Gurkan; Tekin-Koruk, Suda; Dizbay, Murat; Inal, Ayse Seza; Nayman-Alpat, Saygin; Bosilkovski, Mile; Inan, Dilara; Saltoglu, Nese; Abdel-Baky, Laila; Adeva-Bartolome, Maria Teresa; Ceylan, Bahadir; Sacar, Suzan; Turhan, Vedat; Yilmaz, Emel; Elaldi, Nazif; Kocak-Tufan, Zeliha; Ugurlu, Kenan; Dokuzoguz, Basak; Yilmaz, Hava; Gundes, Sibel; Guner, Rahmet; Ozgunes, Nail; Ulcay, Asim; Unal, Serhat; Dayan, Saim; Gorenek, Levent; Karakas, Ahmet; Tasova, Yesim; Usluer, Gaye; Bayindir, Yasar; Kurtaran, Behice; Sipahi, Oguz Resat; Leblebicioglu, Hakan

    2012-03-01

    No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 2.47 months in P1, 6.52 4.15 months in P2, and 5.18 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol. PMID:22155822

  10. Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

    PubMed Central

    Ulu-Kilic, Ay?egl; Kilic, Selim; Karahocagil, Mustafa; Shehata, Ghaydaa; Eren-Tulek, Necla; Yetkin, Funda; Celen, Mustafa Kemal; Ceran, Nurgul; Gul, Hanefi Cem; Mert, Gurkan; Tekin-Koruk, Suda; Dizbay, Murat; Inal, Ayse Seza; Nayman-Alpat, Sayg?n; Bosilkovski, Mile; Inan, Dilara; Saltoglu, Nese; Abdel-Baky, Laila; Adeva-Bartolome, Maria Teresa; Ceylan, Bahad?r; Sacar, Suzan; Turhan, Vedat; Y?lmaz, Emel; Elaldi, Nazif; Kocak-Tufan, Zeliha; U?urlu, Kenan; Dokuzo?uz, Ba?ak; Y?lmaz, Hava; Gundes, Sibel; Guner, Rahmet; Ozgunes, Nail; Ulcay, Asim; Unal, Serhat; Dayan, Saim; Gorenek, Levent; Karakas, Ahmet; Tasova, Yesim; Usluer, Gaye; Bayindir, Yasar; Kurtaran, Behice; Sipahi, Oguz Resat; Leblebicioglu, Hakan

    2012-01-01

    No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 2.47 months in P1, 6.52 4.15 months in P2, and 5.18 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol. PMID:22155822

  11. [Use of antibiotics during pregnancy].

    PubMed

    Nordeng, Stina; Nordeng, Hedvig; Høye, Sigurd

    2016-02-01

    BACKGROUND Antibiotics are the most widely used medication on prescription in pregnancy. It is therefore important to investigate whether antibiotic use in pregnancy can harm the foetus. During the last decade the availability of data from national registries has made it possible to conduct large-scale epidemiological studies. In this article we aimed to review recent studies on the risk of congenital anomalies and miscarriage resulting from the use of antibiotics in pregnancy.METHOD A literature search was conducted in MedLine, Embase and PubMed for the period 1 December 2005 - 1 December 2015. We identified 1 316 articles, of which 23 met the inclusion criteria.RESULTS Recent epidemiological studies have focused on investigating the risks of malformations and pyloric stenosis after exposure to macrolides, nitrofurantoin, penicillins and trimethoprim-sulphamethoxazole. In nine of ten studies that included in total more than 38 000 patients exposed to macrolides, and two studies with more than 7 000 exposed to nitrofurantoin, no significantly increased risk of malformations was discovered. There are some contradictory findings for certain groups of antibiotics with regard to the risk of miscarriage, heart defects and pyloric stenosis.INTERPRETATION Recent studies indicate that erythromycin and nitrofurantoin can be used as second-line drugs in the first trimester. The results from recent studies concur with the recommendations for pregnant women in national guidelines regarding antibiotic use in the primary health service. PMID:26905846

  12. Conjugative transfer of plasmid-located antibiotic resistance genes within the gastrointestinal tract of lesser mealworm larvae, Alphitobius diaperinus (Coleoptera: Tenebrionidae).

    PubMed

    Crippen, Tawni L; Poole, Toni L

    2009-09-01

    The frequency of conjugative transfer of antimicrobial resistance plasmids between bacteria within the gastrointestinal tract of lesser mealworm larvae, a prevalent pest in poultry production facilities, was determined. Lesser mealworm larvae were exposed to a negative bacterial control, a donor Salmonella enterica serotype Newport strain, a recipient Escherichia coli, or both donor and recipient to examine horizontal gene transfer of plasmids. Horizontal gene transfer was validated post external disinfection, via a combination of selective culturing, testing of indole production by spot test, characterization of incompatibility plasmids by polymerase chain reaction, and profiling antibiotic susceptibility by a minimum inhibitory concentration (MIC) assay. Transconjugants were produced in all larvae exposed to both donor and recipient bacteria at frequencies comparable to control in vitro filter mating conjugation studies run concurrently. Transconjugants displayed resistance to seven antibiotics in our MIC panel and, when characterized for incompatibility plasmids, were positive for the N replicon and negative for the A/C replicon. The transconjugants did not display resistance to expanded-spectrum cephalosporins, which were associated with the A/C plasmid. This study demonstrates that lesser mealworm larvae, which infest poultry litter, are capable of supporting the horizontal transfer of antibiotic resistance genes and that this exchange can occur within their gastrointestinal tract and between different species of bacteria under laboratory conditions. This information is essential to science-based risk assessments of industrial antibiotic usage and its impact on animal and human health. PMID:19425825

  13. Prophylactic antibiotics for cardiac pacemaker implantation. A prospective trail.

    PubMed Central

    Muers, M F; Arnold, A G; Sleight, P

    1981-01-01

    A prospective trial was conducted to assess the value of prophylactic antibiotic treatment in preventing postoperative infection of permanent transvenous pacemaker systems. Four hundred and thirty-one patients were randomly allocated to treatment (234) or no-treatment (197) groups. Treated patients received systemic benzylpenicillin and flucloxacillin just before operation and one and six hours afterwards. Nine primary generator pocket infections occurred without evidence of wound dehiscence or skin erosion. Seven infections were in untreated patients and two in treated patients. Antibiotic prophylaxis diminishes the risk of infection after pacemaker implantations. PMID:7317219

  14. Consolidating and Exploring Antibiotic Resistance Gene Data Resources.

    PubMed

    Xavier, Basil Britto; Das, Anupam J; Cochrane, Guy; De Ganck, Sandra; Kumar-Singh, Samir; Aarestrup, Frank Møller; Goossens, Herman; Malhotra-Kumar, Surbhi

    2016-04-01

    The unrestricted use of antibiotics has resulted in rapid acquisition of antibiotic resistance (AR) and spread of multidrug-resistant (MDR) bacterial pathogens. With the advent of next-generation sequencing technologies and their application in understanding MDR pathogen dynamics, it has become imperative to unify AR gene data resources for easy accessibility for researchers. However, due to the absence of a centralized platform for AR gene resources, availability, consistency, and accuracy of information vary considerably across different databases. In this article, we explore existing AR gene data resources in order to make them more visible to the clinical microbiology community, to identify their limitations, and to propose potential solutions. PMID:26818666

  15. Antibiotics, the pill, and pregnancy.

    PubMed Central

    Mastrantonio, M; Minhas, H; Gammon, A

    1999-01-01

    OBJECTIVES: To establish if advice concerning risks of pregnancy when taking oral contraceptive pill and antibiotics is being offered. METHOD: A retrospective audit of notes of 100 female patients aged 15-39 who were prescribed antibiotics. RESULTS: Documentation of use of contraception was noted in 3% of patients. Advice concerning risks and further precautions was noted in this 3% but not in any other records. CONCLUSION: The audit identified a gap in documentation and/or clinical practice in advising women of childbearing age of the risk of conceiving when using oral contraceptive pill and antibiotics. Recommendations are given as to how this may be addressed. Images Figure 1 Figure 2 PMID:10417934

  16. [Alliance against MDRO: safeguarding antibiotics].

    PubMed

    Carlet, J; Rambaud, C; Pulcini, C

    2012-09-01

    Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the 5 next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practitioners, and veterinarians. PMID:22925945

  17. Antibiotic dosing in critical illness.

    PubMed

    McKenzie, Cathrine

    2011-04-01

    Early and effective antibiotic therapy is essential in the management of infection in critical illness. The loading dose is probably the most important dose and is a function of the volume of distribution of the drug and the desired plasma concentration but independent of renal function. Antibiotics are classified in a number of ways that have implications for dosing. Doses of hydrophilic agents such as β-lactams should be increased in the early stages of sepsis as the extravascular space increases. For lipophilic agents such as macrolides, the inflammatory process is less important, although factors such as obesity will affect dosing. Classification can also be based on pharmacodynamic properties. Concentration-dependent antibiotics such as aminoglycosides should be administered by extended interval regimens, which maximize bactericidal effect, minimize nephrotoxicity and allow time between doses for the post-antibiotic effect. The critical factor for time-dependent agents, such as β-lactams, is time above the MIC. Ideally administration of these agents should be continuous, although vascular access availability can restrict infusion time to between 4 and 6 h, which is probably adequate. As well as antibiotic factors, patient factors such as hepatic and renal failure will affect dosing. Hepatic failure will affect antibiotic metabolism, although it is most important in end-stage failure. Renal failure and support will affect drug elimination. Knowledge of these factors is essential. Patient safety and prevention of unnecessary harm is a weighty consideration in critical illness. To ensure effective treatment and minimize adverse effects, therapy should be reviewed daily and adjusted in the light of changes in patient organ function and underlying pathology. PMID:21398304

  18. Antibiotic resistance in acne treatment.

    PubMed

    Humphrey, S

    2012-10-01

    Propionibacterium acnes (P. acnes) is an anaerobic bacteria implicated in the pathogenesis of acne. The last 30 years have witnessed an alarming increase in resistance to antibiotics commonly employed to treat acne. Antibiotic resistance in acne represents a significant international public health concern because resistance can occur in more pathogenic bacteria than P. acnes, and an increase in pathogenic P. acnes has been reported. Current treatment guidelines offer strategies to limit the potential for resistance while achieving optimal outcome in the management of inflammatory and non-inflammatory acne. PMID:23032935

  19. Increase in Resistance to Extended-Spectrum Cephalosporins in Salmonella Isolated from Retail Chicken Products in Japan

    PubMed Central

    Noda, Tamie; Murakami, Koichi; Etoh, Yoshiki; Okamoto, Fuyuki; Yatsuyanagi, Jun; Sera, Nobuyuki; Furuta, Munenori; Onozuka, Daisuke; Oda, Takahiro; Asai, Tetsuo; Fujimoto, Shuji

    2015-01-01

    Extended-spectrum β-lactamase (ESBL)-producing Salmonella are one of the most important public health problems in developed countries. ESBL-producing Salmonella strains have been isolated from humans in Asian countries neighboring Japan, along with strains harboring the plasmid-mediated extended-spectrum cephalosporin (ESC)-resistance gene, ampC (pAmpC). However, only a few studies have investigated the prevalence of ESC-resistant Salmonella in chicken products in Japan, which are the main vehicle of Salmonella transmission. The aim of this study was to investigate the prevalence of ESBL-producing, pAmpC-harboring, or carbapenem-resistant Salmonella in chicken products in Japan. In total, 355 out of 779 (45.6%) chicken product samples collected from 1996–2010 contained Salmonella, resulting in 378 distinct isolates. Of these isolates, 373 were tested for resistance to ESCs, cephamycins, or carbapenems. Isolates that showed resistance to one or more of these antimicrobials were then examined by PCR and DNA sequence analysis for the presence of the blaCMY, blaCTX-M, blaTEM, and blaSHV resistance genes. Thirty-five resistant isolates were detected, including 26 isolates that contained pAmpC (blaCMY-2), and nine ESBL-producing isolates harboring blaCTX-M (n = 4, consisting of two blaCTX-M-2 and two blaCTX-M-15 genes), blaTEM (n = 4, consisting of one blaTEM-20 and three blaTEM-52 genes), and blaSHV (n = 1, blaSHV-12). All pAmpC-harboring and ESBL-producing Salmonella isolates were obtained from samples collected after 2005, and the percentage of resistant isolates increased significantly from 0% in 2004 to 27.9% in 2010 (P for trend = 0.006). This increase was caused in part by an increase in the number of Salmonella enterica subsp. enterica serovar Infantis strains harboring an approximately 280-kb plasmid containing blaCMY-2 in proximity to ISEcp1. The dissemination of ESC-resistant Salmonella containing plasmid-mediated blaCMY-2 in chicken products indicates the need for the development of continuous monitoring strategies in the interests of public health. PMID:25642944

  20. Assessment of anaerobic bacterial diversity and its effects on anaerobic system stability and the occurrence of antibiotic resistance genes.

    PubMed

    Aydin, Sevcan; Ince, Bahar; Ince, Orhan

    2016-05-01

    This study evaluated the link between anaerobic bacterial diversity and, the biodegradation of antibiotic combinations and assessed how amending antibiotic combination and increasing concentration of antibiotics in a stepwise fashion influences the development of resistance genes in anaerobic reactors. The biodegradation, sorption and occurrence of the known antibiotic resistance genes (ARGs) of erythromycin and tetracycline were investigated using the processes of UV-HPLC and qPCR analysis respectively. Ion Torrent sequencing was used to detect microbial community changes in response to the addition of antibiotics. The overall results indicated that changes in the structure of a microbial community lead to changes in biodegradation capacity, sorption of antibiotics combinations and occurrence of ARGs. The enhanced biodegradation efficiency appeared to generate variations in the structure of the bacterial community. The results suggested that controlling the ultimate Gram-negative bacterial community, especially Acinetobacter-related populations, may promote the successful biodegradation of antibiotic combinations and reduce the occurrence of ARGs. PMID:26897411

  1. Transport of sulfonamide antibiotics in small fields during monsoon season

    NASA Astrophysics Data System (ADS)

    Park, J. Y.; Huwe, B.; Kolb, A.; Tenhunen, J.

    2012-04-01

    Transport and fate of 3 sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) were studied in small agricultural land during monsoon period. The experiment has been conducted in 2 typical sandy loam potato fields of South Korea after application of the veterinary antibiotics and bromide. Precipitation was measured by AWS (Automatic Weather Station) near the fields during the whole monsoon season. Runoff generation was estimated by multislot divisors in combination with pressure sensor. Concentration of the target antibiotics and the conservative tracer in runoff, soil-water and soil was determined using HPLC-MS-MS and Br selected electrode. Transport simulation has been performed with Hydrus-2D program which can consider soil characteristics, climate condition, adsorption/desorption and degradation. Results from the measurements and modeling focus on the role of heavy rainfall, of related the ratio of runoff and infiltration in terms of the selected antibiotics distribution and fate. Bromide on topsoil was moved into soil as increasing rainfall loading. On the contrary, the sulfonamides were relatively retarded in upper soil layer owing to adsorption onto soil particles. Different patterns of runoff were observed, and slope and rain intensity was representative factor in this study. Distribution of target pharmaceuticals was strongly dependent on constitution of furrow and ridge in the agricultural fields. Modeling results positively matched with background studies that describe physico-chemical properties of the sulfonamides, interaction between soil and the antibiotic group, solute transport through vadose zone and runoff induction by storm events.

  2. Antibiotics prescribing practices in oral implantology among jordanian dentists. A cross sectional, observational study

    PubMed Central

    2011-01-01

    Background In oral implantology, there is no consensus on the most appropriate regimen for antibiotics prescribing, the decision to prescribe antibiotic is usually based on procedure, patient and clinician related factors. The aim of this study was to investigate the rationale of antibiotic prescribing among Jordanian clinicians who practice oral implantology. Findings The target sample for the study was the 250 Jordan Dental Implant Group members. A five page questionnaire contained 41 questions, both closed and open questions were used to collect data. Statistical analysis was performed using SPSS Windows 16.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were generated. The response rate was (70.4%) 176/250. Mean age was 37.2 yrs, 49.4% always prescribe antibiotics mainly oral amoxicillin and amoxicillin with clavulinic acid. Antibiotics prescribing increased with flap raising, multiple implants and sinus or bone augmentation. Patient medical condition, periodontitis and oral hygiene were the most important clinical factors in antibiotic prescribing, non-clinical factors were; reading scientific materials, courses and lectures, knowledge gained during training, and the effectiveness and previous experience with the drug. Conclusions Wide variations in antibiotics types, routes, dose and duration of administration were found. Recommendations on antibiotic prescribing are needed to prevent antibiotic overprescribing and misuse. PMID:21798040

  3. Dissemination of health information through social networks: Twitter and antibiotics

    PubMed Central

    Scanfeld, Vanessa; Larson, Elaine L.

    2010-01-01

    Background This study reviewed Twitter status updates mentioning antibiotic(s) to determine overarching categories and explore evidence of misunderstanding or misuse of antibiotics. Methods One thousand Twitter status updates mentioning antibiotic(s) were randomly selected for content analysis and categorization. To explore cases of potential misunderstanding or misuse, these status updates were mined for co-occurrence of the following terms: cold + antibiotic(s), extra antibiotic(s), flu + antibiotic(s), leftover antibiotic(s), and share antibiotic(s) and reviewed to confirm evidence of misuse or misunderstanding. Results Of the 1,000 status updates, 971 were categorized into 11 groups: General Use (n=289), Advice/Information (n=157), Side Effects/Negative Reactions (n=113), Diagnosis (n=102), Resistance (n=92), Misunderstanding and/or Misuse (n=55), Positive Reactions (n=48), Animals (n=46), Other (n=42), Wanting/Needing (n=19), and Cost (n=8). Cases of misunderstanding or abuse were identified for the following combinations: flu + antibiotic(s) (n=345), cold + antibiotic(s) (n=302), leftover antibiotic(s) (n=23), share antibiotic(s) (n=10), and extra antibiotic(s) (n=7). Conclusions Social media sites offer means of health information sharing. Further study is warranted to explore how such networks may provide a venue to identify misuse or misunderstanding of antibiotics, promote positive behavior change, disseminate valid information, and explore how such tools can be used to gather real-time health data. PMID:20347636

  4. Antibiotic resistance: a geopolitical issue.

    PubMed

    Carlet, J; Pulcini, C; Piddock, L J V

    2014-10-01

    Antimicrobial resistance (AMR), associated with a lack of new antibiotics, is a major threat. Some countries have been able to contain resistance, but in most countries the numbers of antibiotic-resistant bacteria continue to increase, along with antibiotic consumption by humans and animals. AMR is a global issue, and concerns all decision-makers worldwide. Some initiatives have been undertaken in the last 15 years, in particular by the WHO, the European Centre for Disease Prevention and Control, and the CDC, but those initiatives were partial and poorly implemented, without coordination. Very recently, some important initiatives have been implemented by the WHO. Since 2009, a US and European joint task force, the Trans-Atlantic Task Force on Antibiotic Resistance, has been working on common recommendations. At a national level, some important initiatives have been implemented, in particular in European countries and in the USA. The Chennai declaration, in India, is also a good example of a multidisciplinary and national initiative that was highly political. Finally, several non-governmental non-profit organizations are also very active, and have helped to raise awareness about the problem of AMR. In the future, this global issue will need political involvement and strong cooperation between countries and between international agencies. PMID:25040923

  5. Antibodies: an alternative for antibiotics?

    PubMed

    Berghman, L R; Abi-Ghanem, D; Waghela, S D; Ricke, S C

    2005-04-01

    In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases. PMID:15844826

  6. Spatial mapping of antibiotic resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A serious concern for modern animal production is the fear that feed antimicrobials, such as monensin, increase the potential for high levels of antibiotic resistant (AR) gene prevalence in the manure, which may subsequently be shared with soil communities and eventually be taken up by human pathoge...

  7. Antibiotics and the burn patient.

    PubMed

    Ravat, Franois; Le-Floch, Ronan; Vinsonneau, Christophe; Ainaud, Pierre; Bertin-Maghit, Marc; Carsin, Herv; Perro, Grard

    2011-02-01

    Infection is a major problem in burn care and especially when it is due to bacteria with hospital-acquired multi-resistance to antibiotics. Moreover, when these bacteria are Gram-negative organisms, the most effective molecules are 20 years old and there is little hope of any new product available even in the distant future. Therefore, it is obvious that currently available antibiotics should not be misused. With this aim in mind, the following review was conducted by a group of experts from the French Society for Burn Injuries (SFETB). It examined key points addressing the management of antibiotics for burn patients: when to use or not, time of onset, bactericidia, combination, adaptation, de-escalation, treatment duration and regimen based on pharmacokinetic and pharmacodynamic characteristics of these compounds. The authors also considered antibioprophylaxis and some other key points such as: infection diagnosis criteria, bacterial inoculae and local treatment. French guidelines for the use of antibiotics in burn patients have been designed up from this work. PMID:20510518

  8. Alliance for the Prudent Use of Antibiotics

    MedlinePLUS

    ... Prudent Use of Antibiotics. Launched at the World Economic Forum in Davos, Switzerland, this declaration formally cites ... the author of groundbreaking models to address the economic challenge of developing new antibiotics. Together with his ...

  9. Antibiotic Resistance Could Threaten Surgery, Chemo Patients

    MedlinePLUS

    ... affects all of us," Laxminarayan said. Concern over antibiotic-resistant bacteria is growing. Earlier this year, the Obama ... 2 million people a year become infected by antibiotic-resistant bacteria, and at least 23,000 die from ...

  10. Antibiotics May Not Help After 'Complicated' Appendectomy

    MedlinePLUS

    ... traditional teaching is that all patients with complicated appendicitis receive post-operative antibiotics to reduce the risk ... may not be necessary following surgery for complicated appendicitis." He explained that "antibiotics are not without risks, ...

  11. Unraveling the physiological complexities of antibiotic lethality.

    PubMed

    Dwyer, Daniel J; Collins, James J; Walker, Graham C

    2015-01-01

    We face an impending crisis in our ability to treat infectious disease brought about by the emergence of antibiotic-resistant pathogens and a decline in the development of new antibiotics. Urgent action is needed. This review focuses on a less well-understood aspect of antibiotic action: the complex metabolic events that occur subsequent to the interaction of antibiotics with their molecular targets and play roles in antibiotic lethality. Independent lines of evidence from studies of the action of bactericidal antibiotics on diverse bacteria collectively suggest that the initial interactions of drugs with their targets cannot fully account for the antibiotic lethality and that these interactions elicit the production of reactive oxidants including reactive oxygen species that contribute to bacterial cell death. Recent challenges to this concept are considered in the context of the broader literature of this emerging area of research. Possible ways that this new knowledge might be exploited to improve antibiotic therapy are also considered. PMID:25251995

  12. Antibiotics Often Enough for Kids' Appendicitis

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_156267.html Antibiotics Often Enough for Kids' Appendicitis For early, uncomplicated ... WEDNESDAY, Dec. 16, 2015 (HealthDay News) -- Treatment with antibiotics alone can be a safe and effective alternative ...

  13. What Can Be Done about Antibiotic Resistance?

    MedlinePLUS

    ... Us General Background: What can be done about Antibiotic Resistance? What can I do? Are antibacterial agents, such as antibacterial soaps, a solution? Are antibiotics regulated? Is there any international action on the ...

  14. Antibiotics Might Cause Weight Gain in Kids

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_155294.html Antibiotics Might Cause Weight Gain in Kids Study finds ... 2015 THURSDAY, Oct. 22, 2015 (HealthDay News) -- Repeated antibiotic use is linked to greater weight gains in ...

  15. When and How to Take Antibiotics

    MedlinePLUS

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

  16. Antibiotic-Resistant Gonorrhea: a Growing Threat

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Antibiotic Resistance Recent Health News Related MedlinePlus Health Topics Antibiotic Resistance Gonorrhea About MedlinePlus Site Map FAQs Contact Us ...

  17. Origins and Evolution of Antibiotic Resistance

    PubMed Central

    Davies, Julian; Davies, Dorothy

    2010-01-01

    Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

  18. Certain Antibiotic Might Combat Children's Wheezing Episodes

    MedlinePLUS

    ... news/fullstory_155766.html Certain Antibiotic Might Combat Children's Wheezing Episodes Kids given azithromycin were less likely ... like the common cold. But for especially vulnerable children, one antibiotic in particular -- azithromycin -- might thwart more ...

  19. Collective antibiotic tolerance: Mechanisms, dynamics, and intervention

    PubMed Central

    Meredith, Hannah R.; Srimani, Jaydeep K.; Lee, Anna J.; Lopatkin, Allison J.; You, Lingchong

    2016-01-01

    Bacteria have developed resistance against every antibiotic at an alarming rate, considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics, and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. In contrast, a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming, and inter-population interactions. These strategies can enable rapid population recovery after antibiotic treatment, and provide a time window for otherwise susceptible bacteria to acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy. PMID:25689336

  20. Antibiotic susceptibilities of Listeria: in vitro studies.

    PubMed

    Espaze, E P; Reynaud, A E

    1988-01-01

    Although Listeria is a rather susceptible bacterium, most antibiotics exert a bacteriostatic effect on Listeria monocytogenes. Except for fosfomycin, antibiotic susceptibilities are similar among the species of the genus Listeria. In vitro, bactericidal effect is often achieved by the use of antibiotic combinations. The most commonly used combinations are ampicillin with aminoglycosides. Up until now, there has been no trend towards reduced susceptibility of Listeria to antibiotics. PMID:3047066

  1. Clinical usefulness of the 2010 clinical and laboratory standards institute revised breakpoints for cephalosporin use in the treatment of bacteremia caused by Escherichia coli or Klebsiella spp.

    PubMed

    Ku, Nam Su; Chung, Hae-Sun; Choi, Jun Yong; Yong, Dongeun; Lee, Kyungwon; Kim, June Myung; Chong, Yunsop

    2015-01-01

    We investigated the clinical usefulness of the revised 2010 Clinical and Laboratory Standards Institute (CLSI) breakpoints for Escherichia coli and Klebsiella spp. Of 2,623 patients with bacteremia caused by E. coli or Klebsiella spp., 573 who had been treated appropriately with cephalosporin based on the CLSI 2009 guidelines were enrolled. There were no differences in the rates of treatment failure or mortality between the appropriately and inappropriately treated groups according to the CLSI 2010 guidelines. Additionally, in the matched case-control analysis, the treatment failure rate was higher in bacteremic patients with extended-spectrum ?-lactamase- (ESBL-) producing but cephalosporin-susceptible organisms than in those with ESBL-nonproducing isolates when patients with urinary tract infections were excluded (44% and 0%, resp., P = 0.026). In patients with bacteremia caused by E. coli or Klebsiella spp., the revised CLSI 2010 guidelines did not lead to poorer outcomes. However, ESBL production appeared to be associated with poor clinical outcomes in patients with bacteremia from sources other than the urinary tract. PMID:25793209

  2. A two-protein component 7 alpha-cephem-methoxylase encoded by two genes of the cephamycin C cluster converts cephalosporin C to 7-methoxycephalosporin C.

    PubMed

    Coque, J J; Enguita, F J; Martín, J F; Liras, P

    1995-04-01

    Two genes, cmcI and cmcJ, corresponding to open reading frames 7 and 8 (ORF7 and ORF8) of the cephamycin C cluster of Nocardia lactamdurans encode enzymes that convert cephalosporin C to 7-methoxycephalosporin C. Proteins P7 and P8 (the products of ORF7 and ORF8 expressed in Streptomyces lividans) introduce the methoxyl group at C-7 of the cephem nucleus. Efficient hydroxylation at C-7 and transfer of the methyl group from S-adenosylmethionine require both proteins P7 and P8, although P7 alone shows weak C-7 hydroxylase activity and strong cephalosporin-dependent NADH oxidase activity. Both P7 and P8 appear to be synthesized in a coordinated form by translational coupling of cmcI and cmcJ. Protein P7 contains domains that correspond to conserved sequences in cholesterol 7 alpha-monooxygenases and to the active center of O-methyltransferases by comparison with the crystal structure of catechol-O-methyltransferase. Protein P8 may act as a coupling protein for efficient hydroxylation at C-7 in a form similar to that of the two-component system of Pseudomonas putida p-hydroxyphenylacetate-3-hydroxylase. PMID:7721717

  3. Amino Acid Substitutions at Ambler Position Gly238 in the SHV-1 ?-Lactamase: Exploring Sequence Requirements for Resistance to Penicillins and Cephalosporins

    PubMed Central

    Hujer, Andrea M.; Hujer, Kristine M.; Helfand, Marion S.; Anderson, Vernon E.; Bonomo, Robert A.

    2002-01-01

    Site saturation mutagenesis of the 238 position in the SHV ?-lactamase was performed to identify the complete sequence requirements needed for the extended spectrum ?-lactamase (ESBL) phenotype. MICs (in micrograms per milliliter) in an isogenic background, Escherichia coli DH10B, demonstrated that the Gly238Ala mutation conferred the most resistance to penicillins and cephalosporins. The absolute increase in resistance was greatest against cefotaxime for the Gly238Ala mutant (0.06 to 8 ?g/ml). Except for the strain possessing the Gly238Pro ?-lactamase, ceftazidime MICs were also elevated. None of the mutant SHV ?-lactamases were expressed in as great an amount as the wild-type ?-lactamase. Kinetic analysis of the Gly238Ala mutant revealed that penicillin and cephalosporin substrates have a lower Km for the enzyme because of this mutation. Ampicillin and piperacillin MICs were inversely proportional to the side chain volume of the amino acid in cases larger than Ser, suggesting that steric considerations may be a primary requirement for penicillin resistance. Secondary structural effects explain increased resistance to oxyiminocephalosporins. Based upon this study, we anticipate that additional mutations of Gly238 in the SHV ?-lactamase will continue to be discovered with an ESBL (ceftazidime or cefotaxime resistant) phenotype. PMID:12435703

  4. Antibiotic susceptibility and molecular epidemiology of Acinetobacter calcoaceticusbaumannii complex strains isolated from a referral hospital in northern Vietnam

    PubMed Central

    Van, Trang Dinh; Dinh, Quynh-Dao; Vu, Phu Dinh; Nguyen, Trung Vu; Pham, Ca Van; Dao, Trinh Tuyet; Phung, Cam Dac; Hoang, Ha Thu Thi; Tang, Nga Thi; Do, Nga Thuy; Nguyen, Kinh Van; Wertheim, Heiman

    2014-01-01

    Acinetobacter calcoaceticusbaumannii complex is a common cause of hospital-acquired infections (HAIs) globally, remarkable for its high rate of antibiotic resistance, including to carbapenems. There are few data on the resistance of A. baumannii in Vietnam, which are essential for developing evidence-based treatment guidelines for HAIs. Antibiotic susceptibility testing was conducted by VITEK2, and pulsed-field gel electrophoresis (PFGE) was performed on 66 clinical A. baumannii complex isolates recovered during 2009 at the National Hospital of Tropical Diseases (NHTD), a referral hospital in Hanoi, Vietnam. Basic demographic and clinical data were collected and analysed using descriptive statistics. Most isolates came from lower respiratory tract specimens (59; 89.4%) from intensive care unit (ICU) patients [64/65 (98.5%) with available data] who had been admitted to NHTD for ?2 days [42/46 (91.3%) with available data]. More than 90% of the isolates were resistant to the tested ?-lactamase/?-lactamase inhibitors, cephalosporins, carbapenems, fluoroquinolones and trimethoprim/sulfamethoxazole. Moreover, 25.4% (16/63) were resistant to all tested ?-lactams, quinolones and aminoglycosides. All isolates remained sensitive to colistin and 58.7% were susceptible to tigecycline. Of the 66 isolates, 49 could be classified into eight PFGE types (AH). Every PFGE type, except D, had cluster(s) of three or more isolates with a temporal relationship. In conclusion, these data suggest a significant rise in A. baumannii antibiotic resistance in Vietnam. Clustering within PFGE types supports cross-transmission of A. baumannii within the ICU at NHTD. Increased research and resources in optimising treatment, infection control and antibiotic stewardship are needed. PMID:25540720

  5. Is Clostridium difficile associated with the ‘4C’ antibiotics? A retrospective observational study in diabetic foot ulcer patients

    PubMed Central

    Collier, A; McLaren, J; Godwin, J; Bal, A

    2014-01-01

    Aims Clostridium difficile is an anaerobic cytotoxin-producing bacterium that can cause infectious diarrhoea, pseudomembranous colitis and toxic megacolon. The major risk factors for developing C. difficile infection include recent or current antimicrobial use, diabetes, age over 65, proton pump inhibitor use, immunosuppression and previous infection with C. difficile. Most diabetic foot ulcers are polymicrobial. Methods As a result guidelines advise treatment with broad spectrum antibiotics which include the ‘4C's’ (clindamycin, cephalosporins, co-amoxiclav and ciprofloxacin) which are associated with a higher risk of C. difficile infection. Retrospective observational data (June 2008 to January 2012) for the diabetes foot ulcers were gathered from the Diabetes/Podiatry Clinic database in NHS Ayrshire and Arran and cross-matched with the NHS Ayrshire and Arran Microbiology database. There were 111 patients with mean age 59 years (range 24–94 years), 33 type 1 patients, 78 type 2 patients, mean duration of diabetes 16 years (6 months–37 years) and mean HbA1c 67 mmol/mol (54–108 mmol/mol) [8.3% (7.1–12%)]. Results The total number of days antimicrobials prescribed for all patients was 7938 (mean number of antimicrobial days per patient = 71.5 days). There was one case of C. difficile infection of 111 patients giving an incidence of 1.25 cases per 10,000 patient-days of antibiotics/1 case per 209 foot ulcers. Conclusions Large doses, numbers and greater duration of antibiotic therapy all result in a greater degree of normal gut flora depletion. It is possible that the alterations in gut flora in diabetic foot ulcer patients protect them from antibiotic-induced C. difficile overgrowth. PMID:24499256

  6. Predicting In-Hospital Treatment Failure (≤7 days) in Patients with COPD Exacerbation Using Antibiotics and Systemic Steroids.

    PubMed

    Crisafulli, Ernesto; Torres, Antoni; Huerta, Arturo; Guerrero, Mónica; Gabarrús, Albert; Gimeno, Alexandra; Martinez, Raquel; Soler, Néstor; Fernández, Laia; Wedzicha, Jadwiga A; Menéndez, Rosario

    2016-02-01

    Although pharmacological treatment of COPD exacerbation (COPDE) includes antibiotics and systemic steroids, a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure. The aim of our study was to determine in-hospital predictors of treatment failure (≤ 7 days). Prospective data on 110 hospitalized COPDE patients, all treated with antibiotics and systemic steroids, were collected; on the seventh day of hospitalization, patients were divided into treatment failure (n = 16) or success (n = 94). Measures of inflammatory serum biomarkers were recorded at admission and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, were also recorded. Patients with treatment failure had a worse lung function, with higher serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), interleukin (IL) 8, and IL-10 at admission, and CRP and IL-8 at day 3. Longer length of hospital stay and duration of antibiotic therapy, higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group. In the multivariate analysis, +1 mg/dL of CRP at admission (OR, 1.07; 95% CI, 1.01 to 1.13) and use of penicillins or cephalosporins (OR, 5.63; 95% CI, 1.26 to 25.07) were independent variables increasing risk of treatment failure, whereas cough at admission (OR, 0.20; 95% CI, 0.05 to 0.75) reduces risk of failure. In hospitalized COPDE patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure, while presence of cough has a protective role. PMID:26451913

  7. Do topical antibiotics help corneal epithelial trauma?

    PubMed Central

    King, J. W.; Brison, R. J.

    1993-01-01

    Topical antibiotics are routinely used in emergency rooms to treat corneal trauma, although no published evidence supports this treatment. In a noncomparative clinical trial, 351 patients with corneal epithelial injuries were treated without antibiotics. The infection rate was 0.7%, suggesting that such injuries can be safely and effectively managed without antibiotics. A comparative clinical trial is neither warranted nor feasible. PMID:8268742

  8. New business models for antibiotic innovation.

    PubMed

    So, Anthony D; Shah, Tejen A

    2014-05-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards. PMID:24646116

  9. When and How to Take Antibiotics

    MedlinePLUS

    ... you may have to make return office and pharmacy visits to find the right drug to kill the germ. For more serious infections ... Background About bacteria & antibiotics About antibiotic resistance Multi-drug ... Cost of Resistance Science of Resistance Ecology Antibiotics in ...

  10. Overcoming the current deadlock in antibiotic research.

    PubMed

    Schäberle, Till F; Hack, Ingrid M

    2014-04-01

    Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward. PMID:24698433

  11. Pipeline of Known Chemical Classes of Antibiotics

    PubMed Central

    d’Urso de Souza Mendes, Cristina; de Souza Antunes, Adelaide Maria

    2013-01-01

    Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides.

  12. Get Smart: Know When Antibiotics Work - Urinary Tract Infection

    MedlinePLUS

    ... Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  13. Get Smart: Know When Antibiotics Work - What You Can Do

    MedlinePLUS

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  14. Get Smart: Know When Antibiotics Work - Influenza (Flu)

    MedlinePLUS

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  15. Get Smart: Know When Antibiotics Work - What Everyone Should Know

    MedlinePLUS

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work ...

  16. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

    PubMed

    Brown, David

    2015-12-01

    Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation. PMID:26493767

  17. Surface modeling of soil antibiotics.

    PubMed

    Shi, Wen-Jiao; Yue, Tian-Xiang; Du, Zheng-Ping; Wang, Zong; Li, Xue-Wen

    2016-02-01

    Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0μg/kg, 102.8μg/kg, 106.3μg/kg and 108.7μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2μg/kg (88.6μg/kg, 20.4μg/kg and 39.2μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints. PMID:26613514

  18. Infection, antibiotics, and preterm delivery.

    PubMed

    Locksmith, G; Duff, P

    2001-10-01

    The relationship between genital tract infection and preterm delivery has been established on the basis of biochemical, microbiological, and clinical evidence. In theory, pathogenic bacteria may ascend from the lower reproductive tract into the uterus, and the resulting inflammation leads to preterm labor, rupture of the membranes, and birth. A growing body of evidence suggests that preterm labor and/rupture of the membranes are triggered by micro-organisms in the genital tract and by the host response to these organisms, ie, elaboration of cytokines and proteolytic enzymes. Epidemiologic and in vitro studies do not prove a cause-and-effect relationship between infection and preterm birth. However, the preponderance of evidence indicates that treatment of asymptomatic bacteriuria and symptomatic lower genital tract infections such as bacterial vaginosis (BV), trichomoniasis, gonorrhea, and chlamydia will lower the risk of preterm delivery. Based on current evidence, pregnant women who note an abnormal vaginal discharge should be tested for BV, trichomonas, gonorrhea, and chlamydia. Those who test positive should be treated appropriately. A 3- to 7-day course of antibiotic treatment for asymptomatic bacteriuria during pregnancy is clinically indicated to reduce the risk of pyelonephritis and preterm delivery. Routine screening for chlamydia and gonorrhea should be performed for women at high risk of acquiring sexually transmitted diseases. The practice of routine screening for BV in asymptomatic women who are at low risk for preterm delivery cannot be supported based on evidence from the literature. Routine screening for asymptomatic bacteriuria during pregnancy is cost-effective, particularly in high-prevalence populations. The results of antibiotic trials for the treatment of preterm labor have been inconsistent. In the absence of reasonable evidence that antimicrobial therapy leads to significant prolongation of pregnancy in the setting of preterm labor, antibiotics should be used only for protecting the neonate from group B streptococci sepsis. They should not be used for the purpose of prolonging pregnancy. Multiple investigations have shown that, in patients with preterm premature rupture of the membranes, prophylactic antibiotics are of value in prolonging the latent period between rupture of the membranes and onset of labor and in reducing the incidence of maternal and neonatal infection. The most extensively tested effective antibiotic regimen for prophylaxis involves erythromycin alone or in combination with ampicilln. Controversy still exists regarding the appropriate length and route of antibiotic prophylaxis. PMID:11707017

  19. Metabolic engineering of an industrial polyoxin producer for the targeted overproduction of designer nucleoside antibiotics.

    PubMed

    Qi, Jianzhao; Liu, Jin; Wan, Dan; Cai, You-Sheng; Wang, Yinghu; Li, Shunying; Wu, Pan; Feng, Xuan; Qiu, Guofu; Yang, Sheng-Ping; Chen, Wenqing; Deng, Zixin

    2015-09-01

    Polyoxin and nikkomycin are naturally occurring peptidyl nucleoside antibiotics with potent antifungal bioactivity. Both exhibit similar structural features, having a nucleoside skeleton and one or two peptidyl moieties. Combining the refactoring of the polyoxin producer Streptomyces aureochromogenes with import of the hydroxypyridylhomothreonine pathway of nikkomycin allows the targeted production of three designer nucleoside antibiotics designated as nikkoxin E, F, and G. These structures were determined by NMR and/or high resolution mass spectrometry. Remarkably, the introduction of an extra copy of the nikS gene encoding an ATP-dependent ligase significantly enhanced the production of the designer antibiotics. Moreover, all three nikkoxins displayed improved bioactivity against several pathogenic fungi as compared with the naturally-occurring antibiotics. These data provide a feasible model for high efficiency generation of nucleoside antibiotics related to polyoxins and nikkomycins in a polyoxin cell factory via synthetic biology strategy. PMID:25827606

  20. Antibiotic Treatment Suppresses Rotavirus Infection and Enhances Specific Humoral Immunity

    PubMed Central

    Uchiyama, Robin; Chassaing, Benoit; Zhang, Benyue; Gewirtz, Andrew T.

    2014-01-01

    Background.?Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries. We hypothesized that the gut microbiota might modulate rotavirus infection and/or antibody response and thus potentially play a role in such regional differences. Methods.?The microbiota was ablated via germ-free or antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcription polymerase chain reaction. Diarrhea was scored visually. Humoral responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent spot assay. Results.?Microbiota elimination delayed infection and reduced infectivity by 42%. Antibiotics did not alter ratios of positive-sense to negative-sense strands, suggesting that entry rather than replication was influenced. Antibiotics reduced the diarrhea incidence and duration, indicating that the reduction in the level of rotavirus antigen was biologically significant. Despite lowered antigen level, antibiotics resulted in a more durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody response durability correlated with increased small intestinal rotavirus-specific, immunoglobulin Aproducing antibody-secreting cell concentration in antibiotic-treated mice. Conversely, DSS treatment impaired generation of rotavirus-specific antibodies. Conclusions.?Microbiota ablation resulted in reduced rotavirus infection/diarrhea and a more durable rotavirus antibody response, suggesting that antibiotic administration before rotavirus vaccination could raise low seroconversion rates that correlate with the vaccine's inefficacy in developing regions. PMID:24436449

  1. Methicillin-resistant Staphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration

    PubMed Central

    Franks, Zechariah; Campbell, Robert A.; de Abreu, Adriana Vieira; Holloway, Jeffrey T.; Marvin, James E.; Kraemer, Bjoern F.; Zimmerman, Guy A.; Weyrich, Andrew S.; Rondina, Matthew T.

    2013-01-01

    Summary Methicillin-resistant Staphylococcus aureus (MRSA) induces a pro-thrombotic and pro-inflammatory milieu. Although timely antibiotic administration in MRSA sepsis may improve outcomes by arresting bacterial growth, the effects of antibiotics on mitigating injurious thrombo-inflammatory cellular responses remains unexplored. Using a newly developed human whole blood model and an in vivo mouse model of MRSA infection, we examined how antibiotics inhibit MRSA induced thrombo-inflammatory pathways. Human whole blood was inoculated with MRSA. Thrombin generation and inflammatory cytokine synthesis was measured in the presence or absence of linezolid and vancomycin. C57BL/6 mice were injected with MRSA and the effect of vancomycin administration was examined. MRSA accelerated thrombin generation in a time- and concentration-dependent manner and induced the release of cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1. The increase in thrombin generation and inflammatory responses was mediated through the synthesis of tissue factor and cytokines, respectively, and the release of microparticles. The early administration of antibiotics restored normal thrombin generation patterns and significantly reduced the synthesis of cytokines. In contrast, when antibiotic administration was delayed, thrombin generation and cytokine synthesis were not significantly reduced. In mice infected with MRSA, early antibiotic administration reduced thrombin anti-thrombin complexes and cytokine synthesis, whereas delayed antibiotic administration did not. These data provide novel mechanistic evidence of the importance of prompt antibiotic administration in infectious syndromes. PMID:23348831

  2. Antibiotics induce redox-related physiological alterations as part of their lethality

    PubMed Central

    Dwyer, Daniel J.; Belenky, Peter A.; Yang, Jason H.; MacDonald, I. Cody; Martell, Jeffrey D.; Takahashi, Noriko; Chan, Clement T. Y.; Lobritz, Michael A.; Braff, Dana; Schwarz, Eric G.; Ye, Jonathan D.; Pati, Mekhala; Vercruysse, Maarten; Ralifo, Paul S.; Allison, Kyle R.; Khalil, Ahmad S.; Ting, Alice Y.; Walker, Graham C.; Collins, James J.

    2014-01-01

    Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. PMID:24803433

  3. Antibiotics induce redox-related physiological alterations as part of their lethality.

    PubMed

    Dwyer, Daniel J; Belenky, Peter A; Yang, Jason H; MacDonald, I Cody; Martell, Jeffrey D; Takahashi, Noriko; Chan, Clement T Y; Lobritz, Michael A; Braff, Dana; Schwarz, Eric G; Ye, Jonathan D; Pati, Mekhala; Vercruysse, Maarten; Ralifo, Paul S; Allison, Kyle R; Khalil, Ahmad S; Ting, Alice Y; Walker, Graham C; Collins, James J

    2014-05-20

    Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. PMID:24803433

  4. Biofilm-specific antibiotic resistance.

    PubMed

    Mah, Thien-Fah

    2012-09-01

    Bacterial biofilms are the basis of many persistent diseases. The persistence of these infections is primarily attributed to the increased antibiotic resistance exhibited by the cells within the biofilms. This resistance is multifactorial; there are multiple mechanisms of resistance that act together in order to provide an increased overall level of resistance to the biofilm. These mechanisms are based on the function of wild-type genes and are not the result of mutations. This article reviews the known mechanisms of resistance, including the ability of the biofilm matrix to prevent antibiotics from reaching the cells and the function of individual genes that are preferentially expressed in biofilms. Evidence suggests that these mechanisms have been developed as a general stress response of biofilms that enables the cells in the biofilm to respond to all of the changes in the environment that they may encounter. PMID:22953707

  5. [Antimicrobial peptides and peptide antibiotics].

    PubMed

    Bals, R

    2000-09-15

    Antimicrobial peptides are naturally occurring antibiotics. As part of the innate immune system of vertebrates they have direct antimicrobial function. Further, they can act as mediators of inflammation. Their antimicrobial spectrum covers gram-positive and -negative bacteria as well as fungi and certain viruses.