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Sample records for generation cephalosporin antibiotic

  1. 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. 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

  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. Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008

    PubMed Central

    2010-01-01

    Introduction The objective of the present study was to analyse secular trends in antibiotic consumption and resistance data from a network of 53 intensive care units (ICUs). Methods The study involved prospective unit and laboratory-based surveillance in 53 German ICUs from 2001 through 2008. Data were calculated on the basis of proportions of nonduplicate resistant isolates, resistance densities (that is, the number of resistant isolates of a species per 1,000 patient-days) and an antimicrobial usage density (AD) expressed as daily defined doses (DDD) and normalised per 1,000 patient-days. Results Total mean antibiotic use remained stable over time and amounted to 1,172 DDD/1,000 patient-days (range 531 to 2,471). Carbapenem use almost doubled to an AD of 151 in 2008. Significant increases were also calculated for quinolone (AD of 163 in 2008) and third-generation and fourth-generation cephalosporin use (AD of 117 in 2008). Aminoglycoside consumption decreased substantially (AD of 86 in 2001 and 24 in 2008). Resistance proportions were as follows in 2001 and 2008, respectively: methicillin-resistant Staphylococcus aureus (MRSA) 26% and 20% (P = 0.006; trend test showed a significant decrease), vancomycin-resistant enterococcus (VRE) faecium 2.3% and 8.2% (P = 0.008), third-generation cephalosporin (3GC)-resistant Escherichia. coli 1.2% and 19.7% (P < 0.001), 3GC-resistant Klebsiella pneumoniae 3.8% and 25.5% (P < 0.001), imipenem-resistant Acinetobacter baumannii 1.1% and 4.5% (P = 0.002), and imipenem-resistant K. pneumoniae 0.4% and 1.1%. The resistance densities did not change for MRSA but increased significantly for VRE faecium and 3GC-resistant E. coli and K. pneumoniae. In 2008, the resistance density for MRSA was 3.73, 0.48 for VRE, 1.39 for 3GC-resistant E. coli and 0.82 for K. pneumoniae. Conclusions Although total antibiotic use did not change over time in German ICUs, carbapenem use doubled. This is probably due to the rise in 3GC-resistant E. coli and

  4. Use of fluoroquinolones and third-generation cephalosporins in the emergency department: an 11-year survey.

    PubMed

    Montassier, Emmanuel; Corvec, Stephane; Hardouin, Jean-Benoit; Potel, Gilles; Batard, Eric

    2014-12-01

    Fluoroquinolones and third-generation cephalosporins are particularly prone to select bacterial resistance to antibiotics. We aimed to assess the temporal trends of antibiotic use in the emergency department adults unit of an academic hospital between 2002 and 2012. Antibiotic use was converted in defined daily doses (DDD). The total antibiotic consumption tended to decrease, from 53.1±8.5 to 48.6±11.9 DDD/1000 patient visits (estimate decrease per year, -0.9±0.5 DDD/1000 visits, P=0.07). Use of third-generation cephalosporins increased significantly, from 9.7% of total antibiotic use to 22.6% (estimate per year, 1.2±0.2%, P<0.0001), whereas use of fluoroquinolones decreased from 19.5 to 12.3% (estimate per year, -0.7±0.2%, P<0.003). Given their ability to select bacterial resistance, especially extended-spectrum β-lactamases, particular attention should be paid to increasing use of third-generation cephalosporins in the emergency department. PMID:24487125

  5. In vitro activity, pharmacokinetics, clinical efficacy, safety and pharmacoeconomics of ceftriaxone compared with third and fourth generation cephalosporins: review.

    PubMed

    Bijie, H; Kulpradist, S; Manalaysay, M; Soebandrio, A

    2005-02-01

    Due to their wide spectrum of activity, good pharmacokinetics, established clinical efficacy and high tolerability, cephalosporins are among the most widely used antibiotics worldwide. The third and fourth generation cephalosporins are predominantly parenteral agents, administered two or three times daily, used in the treatment of a wide range of moderate to severe infections. Ceftriaxone, a third generation cephalosporin, is unique in exhibiting an unusually long elimination half-life that allows for once-daily administration. Among third generation cephalosporins, ceftazidime and cefoperazone are unusual among cephalosporins in possessing activity, albeit moderate, against Pseudomonas aeruginosa. However, both of these agents also exhibit marked loss of activity against Gram-negative organisms producing high levels of Class A or C beta-lactamases. Sulperazone, a 1:1 combination of cefoperazone and the beta-lactamase inhibitor sulbactam, is more resistant to attack by Class A beta-lactamases but remains vulnerable to isolates producing Class C beta-lactamases. Ceftriaxone exhibits the widest antibacterial spectrum of third generation cephalosporins and this is reflected in clinical responses. Cefoperazone and sulperazone exhibit the poorest clinical responses. Although the fourth generation cephalosporins cefpirome and cefepime exhibit enhanced stability to bacterial beta-lactamases and marginally enhanced in vitro antibacterial activity over ceftriaxone, there is no clinical advantage in terms of clinical or bacteriological success. The cephalosporins are well tolerated, with few and generally transient adverse effects; the major exception being haematological abnormalities including blood coagulation disorders associated with cefoperazone. Several pharmacoeconomic studies indicate that the once-daily dosing regimen required for ceftriaxone is the major factor responsible for its cost-effectiveness over third and fourth generation cephalosporins. PMID:15828439

  6. Increasing use of third-generation cephalosporins for pneumonia in the emergency department: may some prescriptions be avoided?

    PubMed

    Goffinet, N; Lecadet, N; Cousin, M; Peron, C; Hardouin, J-B; Batard, E; Montassier, E

    2014-07-01

    Third-generation cephalosporins are used to treat inpatients with community-acquired pneumonia. Some of these prescriptions may be avoided, i.e. replaced by agents less likely to promote ESBL-mediated resistance. Our objectives were to assess the recent trend of third-generation cephalosporins use for pneumonia in the emergency department, and the proportion of avoidable prescriptions. This was a retrospective study of patients treated for community-acquired pneumonia in an emergency department, and subsequently hospitalized in non ICU wards. Third-generation cephalosporin prescriptions were presumed unavoidable if they met both criteria: (i) age ≥ 65 yr or comorbid condition, and (ii) allergy or intolerance to penicillin, or failure of penicillin first-line therapy, or treatment with penicillin in three previous months. Prescriptions were otherwise deemed avoidable. The proportion of patients treated with a third generation cephalosporin increased significantly from 13.9 % (6.9-24.1 %) in 2002 to 29.5 % (18.5-42.6 %) in 2012 (OR = 1.07 [1.01-1.14] , P = 0.02). This increase was independent from other factors associated with the prescription of a third-generation cephalosporin (immunocompromising condition, antibacterial therapy in three previous months, fluid resuscitation and REA-ICU class). Treatment with third-generation cephalosporin was avoidable in 118 out of 147 patients (80.3 % [72.7-86.2 %]). On day 7 after admission in the ED, treatment with third-generation cephalosporins was stopped or de-escalated in, respectively, 17 % and 32 % of patients. Antibiotic stewardship programs should be implemented to restrict the third-generation cephalosporins use for pneumonia in the emergency department. PMID:24442608

  7. [2d-generation cephalosporins in the treatment of gram-negative superinfections].

    PubMed

    Mouton, Y; Caillaux, M; Brion, M; Fourrier, A

    1979-01-01

    The second generation cephalosporins are those drugs that are totally or partially resistant to betalactamases (cefamandole, cefuroxime) or the cephamycins (cefoxitine). This property allows them to destroy the enterobacteria resistant to cefalotine and they may have a place in the treatment of certain post-operative infections (abdominal, gynaecological, urinary) on their own or in combination with an aminoglycoside. They also may be of use in combination with an aminoglycoside in the management of secondary septicaemia infections. Outside of these indications which are dependent on the bacteriological findings, their use should be limited even when there is an absence of organisms that are Cefalotine sensitive on the antibiogram. This careful approach (which applies particularly for cefotaxine) may be abandoned once a certain quantity of resistant strains have emerged. For the time being, the second generation cephalosporins ought to be used only for specific indications, and as a general rule should not be first line antibiotic treatment. PMID:44971

  8. Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B.

    PubMed

    Li, Xiang; Li, Haitao; Li, Shengqing; Zhu, Feng; Kim, Dong Joon; Xie, Hua; Li, Yan; Nadas, Janos; Oi, Naomi; Zykova, Tatyana A; Yu, Dong Hoon; Lee, Mee-Hyun; Kim, Myoung Ok; Wang, Lei; Ma, Weiya; Lubet, Ronald A; Bode, Ann M; Dong, Ziming; Dong, Zigang

    2012-12-01

    Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential 'off' target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 µM) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B. PMID:22962305

  9. A novel family VIII carboxylesterase hydrolysing third- and fourth-generation cephalosporins.

    PubMed

    Jeon, Jeong Ho; Lee, Hyun Sook; Lee, Jung Hun; Koo, Bon-Sung; Lee, Chang-Muk; Lee, Sang Hee; Kang, Sung Gyun; Lee, Jung-Hyun

    2016-01-01

    A metagenomic library was constructed from a soil sample of spindle tree-rhizosphere. From this library, one clone with esterase activity was selected. The sequence analysis revealed an open reading frame (EstSTR1) encoded protein of 390 amino acids. EstSTR1 is a family VIII carboxylesterase and retains the S-X-X-K motif conserved in both family VIII carboxylesterases and class C β-lactamases. The estSTR1 gene was overexpressed in E. coli and the recombinant protein was purified by purified by metal chelating affinity chromatography and size-exclusion chromatography. EstSTR1 hydrolysed p-nitrophenyl esters, exhibited the highest activity toward p-nitrophenyl butyrate. Furthermore, EstSTR1 could hydrolyse third- and fourth-generation cephalosporins (cefotaxime and cefepime) as well as first-generation cephalosporin (cephalothin). Site-directed mutagenesis studies revealed that a catalytic residue, Ser71, of EstSTR1 plays an essential role in hydrolysing both antibiotics and p-nitrophenyl esters. We demonstrate that a metagenome-derived carboxylesterase displays β-lactam-hydrolysing activities toward third- and fourth-generation cephalosporins. PMID:27186489

  10. PBP 4 Mediates High-Level Resistance to New-Generation Cephalosporins in Staphylococcus aureus.

    PubMed

    Chan, Liana C; Gilbert, Aubre; Basuino, Li; da Costa, Thaina M; Hamilton, Stephanie M; Dos Santos, Katia R; Chambers, Henry F; Chatterjee, Som S

    2016-07-01

    Staphylococcus aureus is an important cause of both hospital- and community-associated methicillin-resistant S. aureus (MRSA) infections worldwide. β-Lactam antibiotics are the drugs of choice to treat S. aureus infections, but resistance to these and other antibiotics make treatment problematic. High-level β-lactam resistance of S. aureus has always been attributed to the horizontally acquired penicillin binding protein 2a (PBP 2a) encoded by the mecA gene. Here, we show that S. aureus can also express high-level resistance to β-lactams, including new-generation broad-spectrum cephalosporins that are active against methicillin-resistant strains, through an uncanonical core genome-encoded penicillin binding protein, PBP 4, a nonessential enzyme previously considered not to be important for staphylococcal β-lactam resistance. Our results show that PBP 4 can mediate high-level resistance to β-lactams. PMID:27067335

  11. Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center

    PubMed Central

    2014-01-01

    Background Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. Methods The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. Results Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p < 0.001). There was a significant intervention-related decrease in the use of cephalosporins and fluoroquinolones (p < 0.001) outperforming the decreasing baseline trend. Trend changes observed in some of the control departments were smaller, and the difference between trend changes in the medical service and those in control departments were highly significant for overall use and cephalosporin use reductions (p < 0.001) as well as for the increasing use of penicillins (p < 0.001). Mean use density levels (in RDD per 100 patient days) dropped for cephalosporins from 16.3 to 10.3 (−37%) and for fluoroquinolones from 17.7 to 10.1 (−43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. Conclusion An

  12. Stability of frozen stock solutions of beta-lactam antibiotics, cephalosporins, tetracyclines and quinolones used in antibiotic residue screening and antibiotic susceptibility testing.

    PubMed

    Okerman, Lieve; Van Hende, Johan; De Zutter, Lieven

    2007-03-14

    The stability of frozen stock solutions of antibiotics belonging to three different families was evaluated using an agar diffusion test, with Bacillus subtilis as a test strain. Diameters of inhibition zones were measured at monthly intervals during 6 months, and the decline in active substance was calculated. Penicillin and amoxicillin lost nearly half of their potency, the cephalosporins ceftiofur and cefapirin one quarter, but ampicillin was more stable. The quinolones flumequine, enrofloxacin and marbofloxacin were relatively stable; the loss of activity was less than 10% after 6 months of preservation at -20 degrees C. This was also the case for doxycycline and chlortetracycline, while oxytetracycline and tetracycline lost about 25% of their potency. When used in microbiology, i.e. for residue testing or for determination of minimum inhibitory concentrations, a diminution of activity less than 25% will not be noticed. For these applications, the four tetracyclines and three quinolones tested can be kept for 6 months at -20 degrees C, while the beta-lactam antibiotics should be discarded after 3 months. Standard stock solutions of beta-lactam antibiotics and cephalosporins should preferably be used the same day when they are intended for quantitative residue analysis. PMID:17386725

  13. Emergence of resistance to third-generation cephalosporin in Shigella--a case report.

    PubMed

    Mandal, Jharna; Mondal, Nivedita; Mahadevan, S; Parija, Subhash Chandra

    2010-08-01

    The emergence of ciprofloxacin resistance in Shigella has shifted the attention to cephalosporins. The first occurrence of third generation cephalosporin-resistant Shigella flexneri was from France. This article reports the first case of cephalosporin-resistant S. flexneri from India. A 12-month-old child was admitted for a 20-day episode of loose stools, non-fetid, with mucus and blood. The stool sample showed the presence of blood and mucus and S. flexneri which was resistant to Ampicillin, Nalidixic acid, Ciprofloxacin, Furoxone, Ceftriaxone and sensitive only to Cefoperazone and sulbactam combination. The child was promptly admitted and treated with a combination of Cefoperazone and sulbactam. The use of this combination was met with success in the present case, and may be considered as a temporary answer to the emerging cephalosporin-resistance. PMID:19955258

  14. Kirby-Bauer disc approximation to detect inducible third-generation cephalosporin resistance in Enterobacteriaceae.

    PubMed

    Qin, Xuan; Weissman, Scott J; Chesnut, Mary Frances; Zhang, Bei; Shen, Lisong

    2004-07-15

    Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect using standard methods of either Kirby-Bauer disc diffusion (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This difficulty is due to genetic differences in resistance determinants, differences in levels of gene expression, and variation in spectra of enzymatic activity against the substrate beta-lactams used for susceptibility testing. We have examined 95 clinical isolates reportedly susceptible to ceftazidime and ceftriaxone, as originally determined by either KBDD or MIC methods. The organisms studied here were isolated in 2002 from two pediatric hospital centers (Seattle, USA and Shanghai, China). They belong to the inducible beta-lactamase producing Gram-negative bacilli, such as Enterobacter spp., Citrobacter spp., Serratia spp., Morganella spp., Providencia spp., and Proteus vulgaris. A Kirby-Bauer disc approximation (KBDA) method identified inducible phenotypes of third-generation cephalosporin resistance in 76% of isolates, which would otherwise be considered susceptible by standard KBDD methods. PMID:15256000

  15. Biosynthesis of Cephalosporin C

    PubMed Central

    Ott, J. L.; Godzeski, C. W.; Pavey, D.; Farran, J. D.; Horton, D. R.

    1962-01-01

    A series of complex and synthetic media have been developed that are suitable for the production of cephalosporin C and cephalosporin N by a mutant strain of Cephalosporium (C.M.I. 49,137). dl-Methionine increased the yield of both antibiotics, with more effect on cephalosporin N. l-Cystine had a greater enhancing effect on formation of cephalosporin C than on formation of cephalosporin N in synthetic media; serine increased yields of cephalosporin C under certain conditions. Disaccharides or polysaccharides appeared to be the best source for carbohydrates. No evidence was found for precursor action such as is found in penicillin fermentations. The ability of resting cells to produce antibiotic was demonstrated. PMID:16349624

  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 β-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 β-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. ESBL Detection: Comparison of a Commercially Available Chromogenic Test for Third Generation Cephalosporine Resistance and Automated Susceptibility Testing in Enterobactericeae

    PubMed Central

    El-Jade, Mohamed Ramadan; Parcina, Marijo; Schmithausen, Ricarda Maria; Stein, Christoph; Meilaender, Alina; Hoerauf, Achim; Molitor, Ernst

    2016-01-01

    Rapid detection and reporting of third generation cephalosporine resistance (3GC-R) and of extended spectrum betalactamases in Enterobacteriaceae (ESBL-E) is a diagnostic and therapeutic priority to avoid inefficacy of the initial antibiotic regimen. In this study we evaluated a commercially available chromogenic screen for 3GC-R as a predictive and/or confirmatory test for ESBL and AmpC activity in clinical and veterinary Enterobacteriaceae isolates. The test was highly reliable in the prediction of cefotaxime and cefpodoxime resistance, but there was no correlation with ceftazidime and piperacillin/tazobactam minimal inhibitory concentrations. All human and porcine ESBL-E tested were detected with exception of one genetically positive but phenotypically negative isolate. By contrast, AmpC detection rates lay below 30%. Notably, exclusion of piperacillin/tazobactam resistant, 3GC susceptible K1+ Klebsiella isolates increased the sensitivity and specificity of the test for ESBL detection. Our data further imply that in regions with low prevalence of AmpC and K1 positive E. coli strains chromogenic testing for 3GC-R can substitute for more time consuming ESBL confirmative testing in E. coli isolates tested positive by Phoenix or VITEK2 ESBL screen. We, therefore, suggest a diagnostic algorithm that distinguishes 3GC-R screening from primary culture and species-dependent confirmatory ESBL testing by βLACTATM and discuss the implications of MIC distribution results on the choice of antibiotic regimen. PMID:27494134

  19. ESBL Detection: Comparison of a Commercially Available Chromogenic Test for Third Generation Cephalosporine Resistance and Automated Susceptibility Testing in Enterobactericeae.

    PubMed

    El-Jade, Mohamed Ramadan; Parcina, Marijo; Schmithausen, Ricarda Maria; Stein, Christoph; Meilaender, Alina; Hoerauf, Achim; Molitor, Ernst; Bekeredjian-Ding, Isabelle

    2016-01-01

    Rapid detection and reporting of third generation cephalosporine resistance (3GC-R) and of extended spectrum betalactamases in Enterobacteriaceae (ESBL-E) is a diagnostic and therapeutic priority to avoid inefficacy of the initial antibiotic regimen. In this study we evaluated a commercially available chromogenic screen for 3GC-R as a predictive and/or confirmatory test for ESBL and AmpC activity in clinical and veterinary Enterobacteriaceae isolates. The test was highly reliable in the prediction of cefotaxime and cefpodoxime resistance, but there was no correlation with ceftazidime and piperacillin/tazobactam minimal inhibitory concentrations. All human and porcine ESBL-E tested were detected with exception of one genetically positive but phenotypically negative isolate. By contrast, AmpC detection rates lay below 30%. Notably, exclusion of piperacillin/tazobactam resistant, 3GC susceptible K1+ Klebsiella isolates increased the sensitivity and specificity of the test for ESBL detection. Our data further imply that in regions with low prevalence of AmpC and K1 positive E. coli strains chromogenic testing for 3GC-R can substitute for more time consuming ESBL confirmative testing in E. coli isolates tested positive by Phoenix or VITEK2 ESBL screen. We, therefore, suggest a diagnostic algorithm that distinguishes 3GC-R screening from primary culture and species-dependent confirmatory ESBL testing by βLACTATM and discuss the implications of MIC distribution results on the choice of antibiotic regimen. PMID:27494134

  20. Rapid and sensitive high-performance liquid chromatographic determination of four cephalosporin antibiotics in pharmaceuticals and body fluids.

    PubMed

    Samanidou, V F; Hapeshi, E A; Papadoyannis, I N

    2003-05-01

    A rapid, accurate and sensitive method has been developed and validated for the quantitative simultaneous determination of four cephalosporins, cephalexin and cefadroxil (first-generation), cefaclor (second-generation) and cefataxim (third-generation), in pharmaceuticals as well as in human blood serum and urine. A Spherisorb ODS-2 250 x 4-mm, 5-microm analytical column was used with an eluting system consisting of a mixture of acetate buffer (pH 4.0)-CH(3)OH 78-22% (v/v) at a flow-rate 1.2 ml/min. Detection was performed with a variable wavelength UV-Vis detector at 265 nm resulting in limit of detection of 0.2 ng for cefadroxil and cephalexin, but only 0.1 ng for cefotaxime and cefaclor per 20-microl injection. Hydrochlorothiazide (HCT) (6-chloro-3,4-dihydro-7 sulfanyl-2H-1,2,4-benzothiadiazine-1-1-dioxide) was used as internal standard at a concentration of 2 ng/microl. A rectilinear relationship was observed up to 8, 5, 12 and 35 ng/microl for cefadroxil, cefotaxime, cefaclor, cephalexin, respectively. Analysis time was less than 7 min. The statistical evaluation of the method was examined by means of within-day repeatability (n=8) and day-to-day precision (n=9) and was found to be satisfactory with high accuracy and precision. The method was applied to the determination of the cephalosporins in commercial pharmaceuticals and in biological fluids: human blood serum after solid-phase extraction and urine simply after filtration and dilution. Recovery of analytes in spiked samples was in the range from 76.3 to 112.0%, over the range of 1-8 ng/microl. PMID:12668080

  1. In Vitro Activity of TD-1792, a Multivalent Glycopeptide-Cephalosporin Antibiotic, against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species

    PubMed Central

    Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.

    2012-01-01

    TD-1792 is a multivalent glycopeptide-cephalosporin heterodimer antibiotic with potent activity against Gram-positive bacteria. We tested TD-1792 against 377 anaerobes and 34 strains of Corynebacterium species. Against nearly all Gram-positive strains, TD-1792 had an MIC90 of 0.25 μg/ml and was typically 3 to 7 dilutions more active than vancomycin and daptomycin. PMID:22290981

  2. 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

  3. 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

  4. Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints.

    PubMed

    Hsieh, Chih-Chia; Lee, Chung-Hsun; Li, Ming-Chi; Hong, Ming-Yuan; Chi, Chih-Hsien; Lee, Ching-Chi

    2016-04-01

    Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC≤1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC≤8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC≤1mg/L. PMID:27005458

  5. Comprehensive analysis of ß-lactam antibiotics including penicillins, cephalosporins, and carbapenems in poultry muscle using liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Berendsen, Bjorn J A; Gerritsen, Henk W; Wegh, Robin S; Lameris, Steven; van Sebille, Ralph; Stolker, Alida A M; Nielen, Michel W F

    2013-09-01

    A comprehensive method for the quantitative residue analysis of trace levels of 22 ß-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, in poultry muscle by liquid chromatography in combination with tandem mass spectrometric detection is reported. The samples analyzed for ß-lactam residues are hydrolyzed using piperidine in order to improve compound stability and to include the total residue content of the cephalosporin ceftifour. The reaction procedure was optimized using a full experimental design. Following detailed isotope labeling, tandem mass spectrometry studies and exact mass measurements using high-resolution mass spectrometry reaction schemes could be proposed for all ß-lactams studied. The main reaction occurring is the hydrolysis of the ß-lactam ring under formation of the piperidine substituted amide. For some ß-lactams, multiple isobaric hydrolysis reaction products are obtained, in accordance with expectations, but this did not hamper quantitative analysis. The final method was fully validated as a quantitative confirmatory residue analysis method according to Commission Decision 2002/657/EC and showed satisfactory quantitative performance for all compounds with trueness between 80 and 110% and within-laboratory reproducibility below 22% at target level, except for biapenem. For biapenem, the method proved to be suitable for qualitative analysis only. PMID:23430185

  6. Cephalosporins in veterinary medicine - ceftiofur use in food animals.

    PubMed

    Hornish, Rex E; Kotarski, Susan F

    2002-07-01

    Cephalosporins are an important class of antibacterial agents in use today for both humans and animals. Four generations of cephalosporins have evolved, all of which contain the beta-lactam sub-structure first found in penicillin. The range of cephalosporins available for use in food-producing animals, which is the subject of this review, is limited compared to humans. A few first- and second-generation cephalosporins are approved worldwide strictly for treatment of mastitis infections in dairy cattle. A third-generation cephalosporin, ceftiofur, and a fourth-generation cephalosporin, cefquinome, have been developed strictly for veterinary use. Cefquinome has been approved in several countries for the treatment of respiratory disease in cattle and swine, foot rot in cattle and for mastitis in dairy cattle. Ceftiofur has worldwide approvals for respiratory disease in swine, ruminants (cattle, sheep and goats) and horses and has also been approved for foot rot and metritis infections in cattle. Ceftiofur has also been approved in various countries for early mortality infections in day-old chicks and turkey poults. This review summarizes cephalosporin use in general terms, and provides an overview of ceftiofur, in terms of its spectrum of activity, indications, metabolism, and degradation in the environment. The safety of ceftiofur is also reviewed, with respect to food-animal residues, rapid metabolism and degradation, and non-persistence of ceftiofur in the environment. The environmental fragility of cephalosporins have not been explored generally, but may be an important characteristic of this antibiotic class with respect to safety of use in animals. PMID:12052187

  7. Extended Spectrum Beta Lactamase producing Cephalosporin resistant Salmonella Typhi, reported from Rawalpindi, Pakistan.

    PubMed

    Munir, Tehmina; Lodhi, Munir; Ansari, Jawad Khaliq; Andleeb, Saadia; Ahmed, Mushtaq

    2016-08-01

    Typhoid is endemic in many parts of southeast Asia. Due to the resistance of the organism to first line of antibiotics (ampicillin, chloramphenicol, cotrimoxazole) as well as to fluoroquinolones, third generation cephalosporins have been in use for the empiric treatment of typhoid for years. However an increasing incidence of Salmonella Typhi is being reported sporadically from various regions. We report a case of typhoid due to Salmonella Typhi which was non-responsive to treatment with a cephalosporin, was found to be multidrug resistant and resistant to ciprofloxacin and third generation cephalosporin as well. The patient was finally treated successfully with intravenous administration of a carbapenem. PMID:27524545

  8. 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).

  9. [Advances in the regulation of cephalosporin C biosynthesis - A review].

    PubMed

    Liu, Jiajia; Liu, Gang

    2016-03-01

    The beta-lactam antibiotic cephalosporin C is produced industrially by Acremonium chrysogenum. Its derivative 7-aminocephalosporanic acid (7-ACA) is the intermediate of most chemical modification cephalosporins that are the most frequently used antibiotics for the therapy of infectious diseases. Due to its importance, the biosynthetic pathway of cephalosporin C has been elucidated in Acremonium chrysogenum. To improve the yield of cephalosporin C and reduce the cost of production, recent studies have been focused on the sophisticated regulation of cephalosporin C biosynthesis. In this review, recent advances in cephalosporin C biosynthesis and regulation are summarized. PMID:27382789

  10. Endocarditis due to ampicillin-resistant nontyphoid Salmonella: cure with a third-generation cephalosporin.

    PubMed

    Rodriguez, C; Olcoz, M T; Izquierdo, G; Moreno, S

    1990-01-01

    A case of ampicillin-resistant salmonella bacteremia complicated by endocarditis in a 78-year-old man is presented. Previous rheumatic valvular heart disease and the lack of response to initial treatment with chloramphenicol prompted us to consider this diagnosis. There was a good clinical response after treatment with ceftriaxone alone and corresponding improvement on the echocardiogram. This case demonstrates the possible endovascular complications of salmonella bacteremia in elderly people and that endocarditis should be included among the invasive infections due to ampicillin-resistant Salmonella that could potentially be treated with the newer cephalosporins. PMID:2237123

  11. Fluoroquinolone and Third-Generation-Cephalosporin Resistance among Hospitalized Patients with Urinary Tract Infections Due to Escherichia coli: Do Rates Vary by Hospital Characteristics and Geographic Region?

    PubMed

    Bidell, Monique R; Palchak, Melissa; Mohr, John; Lodise, Thomas P

    2016-05-01

    This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rates exceeded 25% regardless of geographic location or hospital characteristics. The findings suggest that fluoroquinolones should be reserved and third-generation cephalosporins be used with caution as empirical agents for hospitalized patients with UTIs due to E. coli. PMID:26926640

  12. 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

  13. 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...

  14. Characterization of the oral absorption of beta-lactam antibiotics. I. Cephalosporins: determination of intrinsic membrane absorption parameters in the rat intestine in situ.

    PubMed

    Sinko, P J; Amidon, G L

    1988-10-01

    The oral absorption of five cephalosporin antibiotics, cefaclor, cefadroxil, cefatrizine, cephalexin, and cephradine, has been studied using a single-pass intestinal perfusion technique in rats. Intrinsic membrane absorption parameters, "unbiased" by the presence of an aqueous permeability (diffusion or stagnant layer), have been calculated utilizing a boundary layer mathematical model. The resultant intrinsic membrane absorption parameters are consistent with a significant carrier-mediated, Michaelis-Menten-type kinetic mechanism and a small passive component in the jejunum. Cefaclor colon permeability is low and does not exhibit concentration dependent behavior. The measured carrier parameters (+/- SD) for the jejunal perfusions are as follows: cefaclor, J*max = 21.3 (+/- 4.0), Km = 16.1 (+/- 3.6), P*m = 0, and P*c = 1.32 (+/- 0.07); cefadroxil, J*max = 8.4 (+/- 0.8), Km = 5.9 (+/- 0.8), P*m = 0, and P*c = 1.43 (+/- 0.10); cephalexin, J*max = 9.1 (+/- 1.2), Km = 7.2 (+/- 1.2), P*m = 0, and P*c = 1.30 (+/- 0.10); cefatrizine, J*max = 0.73 (+/- 0.19), Km = 0.58 (+/- 0.17), P*m = 0.17 (+/- 0.03), and P*c = 1.25 (+/- 0.10); and cephradine, J*max = 1.57 (+/- 0.84), Km = 1.48 (+/- 0.75), P*m = 0.25 (+/- 0.07), and P*c = 1.06 (+/- 0.08). The colon absorption parameter for cefaclor is P*m = 0.36 (+/- 0.06, where J*max (mM) is the maximal flux, Km (mM) is the Michaelis constant, P*m is the passive membrane permeability, and P*c is the carrier permeability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3244617

  15. Ease-of-use protocol for the rapid detection of third-generation cephalosporin resistance in Enterobacteriaceae isolated from blood cultures using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.

    PubMed

    Foschi, C; Compri, M; Smirnova, V; Denicolò, A; Nardini, P; Tamburini, M V; Lombardo, D; Landini, M P; Ambretti, S

    2016-06-01

    An ease-of-use protocol for the identification of resistance against third-generation cephalosporins in Enterobacteriaceae isolated from blood culture bottles was evaluated using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. A cefotaxime hydrolysis assay from chocolate agar subcultures using antibiotic discs and without inoculum standardization was developed for routine work flow, with minimal hands-on time. This assay showed good performance in distinguishing between cefotaxime-susceptible and cefotaxime-resistant strains, with excellent results for Escherichia coli (sensitivity 94.7%, specificity 100%). However, cefotaxime resistance was not detected reliably in Enterobacteriaceae expressing AmpC genes or carbapenemase-producing Klebsiella pneumoniae. PMID:27105753

  16. Reduction of vancomycin-resistant enterococcal infections by limitation of broad-spectrum cephalosporin use in a trauma and burn intensive care unit.

    PubMed

    May, A K; Melton, S M; McGwin, G; Cross, J M; Moser, S A; Rue, L W

    2000-09-01

    Both vancomycin and third-generation cephalosporin use are believed to contribute to a rise in vancomycin-resistant enterococci (VRE) infections. In 1998, the largest number of VRE infections in our hospital occurred in the trauma/burn intensive care unit (TBICU), accounting for nearly 20% of hospital infections. In an attempt to control the VRE infection rate, antibiotic protocols for prophylaxis, empiric, and definitive therapy were initiated during the final quarter of 1998 to minimize cephalosporin use by the introduction of piperacillin/tazobactam. Therefore, we undertook a study of the VRE infection rate for the TBICU in relation to vancomycin, piperacillin/tazobactam, piperacillin, third-generation cephalosporin, and total cephalosporin use before and after efforts to limit cephalosporins. These data were compared to those in the medical and surgical intensive care units. During 1998, seven VRE infections occurred in the TBICU. Following initiation of antibiotic protocols, one case of VRE infection occurred in the subsequent month and no cases in the 17 months since. The decrease in the VRE infection rate corresponded with a significant increase in the use of piperacillin/tazobactam and a reduction in third-generation and total cephalosporin use. In contrast, cephalosporin use in the medical and surgical intensive care units remains significantly higher than in the TBICU, and neither unit has had a reduction in their VRE infection rates. PMID:11028540

  17. Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code.

    PubMed

    Liu, Anne; Tran, Lillian; Becket, Elinne; Lee, Kim; Chinn, Laney; Park, Eunice; Tran, Katherine; Miller, Jeffrey H

    2010-04-01

    We have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire KEIO collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display significantly increased sensitivity to at least one of the antibiotics. We used this reduced set of strains to determine a profile for eight additional antibiotics (spectinomycin, cephradine, aztreonem, colistin, neomycin, enoxacin, tobramycin, and cefoxitin). The profiles for the 22 antibiotics represent a growing catalog of sensitivity fingerprints that can be separated into two components, multidrug-resistant mutants and those mutants that confer relatively specific sensitivity to the antibiotic or type of antibiotic tested. The latter group can be represented by a set of 20 to 60 strains that can be used for the rapid typing of antibiotics by generating a virtual bar code readout of the specific sensitivities. Taken together, these data reveal the complexity of intrinsic resistance and provide additional targets for the design of codrugs (or combinations of drugs) that potentiate existing antibiotics. PMID:20065048

  18. Occurrence and genetic characteristics of third-generation cephalosporin-resistant Escherichia coli in Swiss retail meat.

    PubMed

    Vogt, Debora; Overesch, Gudrun; Endimiani, Andrea; Collaud, Alexandra; Thomann, Andreas; Perreten, Vincent

    2014-10-01

    Prevalence and genetic relatedness were determined for third-generation cephalosporin-resistant Escherichia coli (3GC-R-Ec) detected in Swiss beef, veal, pork, and poultry retail meat. Samples from meat-packing plants (MPPs) processing 70% of the slaughtered animals in Switzerland were purchased at different intervals between April and June 2013 and analyzed. Sixty-nine 3GC-R-Ec isolates were obtained and characterized by microarray, PCR/DNA sequencing, Multi Locus Sequence Typing (MLST), and plasmid replicon typing. Plasmids of selected strains were transformed by electroporation into E. coli TOP10 cells and analyzed by plasmid MLST. The prevalence of 3GC-R-Ec was 73.3% in chicken and 2% in beef meat. No 3GC-R-Ec were found in pork and veal. Overall, the bla(CTX-M-1) (79.4%), bla(CMY-2) (17.6%), bla(CMY-4) (1.5%), and bla(SHV-12) (1.5%) β-lactamase genes were detected, as well as other genes conferring resistance to chloramphenicol (cmlA1-like), sulfonamides (sul), tetracycline (tet), and trimethoprim (dfrA). The 3GC-R-Ec from chicken meat often harbored virulence genes associated with avian pathogens. Plasmid incompatibility (Inc) groups IncI1, IncFIB, IncFII, and IncB/O were the most frequent. A high rate of clonality (e.g., ST1304, ST38, and ST93) among isolates from the same MPPs suggests that strains persist at the plant and spread to meat at the carcass-processing stage. Additionally, the presence of the blaCTX-M-1 gene on an IncI1 plasmid sequence type 3 (IncI1/pST3) in genetically diverse strains indicates interstrain spread of an epidemic plasmid. The bla(CMY-2) and bla(CMY-4) genes were located on IncB/O plasmids. This study represents the first comprehensive assessment of 3GC-R-Ec in meat in Switzerland. It demonstrates the need for monitoring contaminants and for the adaptation of the Hazard Analysis and Critical Control Point concept to avoid the spread of multidrug-resistant bacteria through the food chain. PMID:24773305

  19. 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 μg/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

  20. 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 pneumonia—data 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

  1. 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...

  2. Industrial enzymatic production of cephalosporin-based beta-lactams.

    PubMed

    Barber, Michael S; Giesecke, Ulrich; Reichert, Arno; Minas, Wolfgang

    2004-01-01

    Cephalosporins are chemically closely related to penicillins both work by inhibiting the cell wall synthesis of bacteria. The first generation cephalosporins entered the market in 1964. Second and third generation cephalosporins were subsequently developed that were more powerful than the original products. Fourth generation cephalosporins are now reaching the market. Each newer generation of cephalosporins has greater Gram-negative antimicrobial properties than the preceding generation. Conversely, the 'older' generations of cephalosporins have greater Gram-positive (Staphylococcus and Streptococcus) coverage than the 'newer' generations. Frequency of dosing decreases and palatability generally improve with increasing generations. The advent of fourth generation cephalosporins with the launch of cefepime extended the spectrum against Gram-positive organisms without a significant loss of activity towards Gram-negative bacteria. Its greater stability to beta-lactamases increases its efficacy against drug-resistant bacteria. In this review we present the current situation of this mature market. In addition, we present the current state of the technologies employed for the production of cephalosporins, focusing on the new and environmentally safer 'green' routes to the products. Starting with the fermentation and purification of CPC, enzymatic conversion in conjunction with aqueous chemistry will lead to some key intermediates such as 7-ACA, TDA and TTA, which then can be converted into the active pharmaceutical ingredient (API), again applying biocatalytic technologies and aqueous chemistry. Examples for the costing of selected products are provided as well. PMID:15719556

  3. Antibiotic Sensitivity Profiles Determined with an Escherichia coli Gene Knockout Collection: Generating an Antibiotic Bar Code ▿ †

    PubMed Central

    Liu, Anne; Tran, Lillian; Becket, Elinne; Lee, Kim; Chinn, Laney; Park, Eunice; Tran, Katherine; Miller, Jeffrey H.

    2010-01-01

    We have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire KEIO collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display significantly increased sensitivity to at least one of the antibiotics. We used this reduced set of strains to determine a profile for eight additional antibiotics (spectinomycin, cephradine, aztreonem, colistin, neomycin, enoxacin, tobramycin, and cefoxitin). The profiles for the 22 antibiotics represent a growing catalog of sensitivity fingerprints that can be separated into two components, multidrug-resistant mutants and those mutants that confer relatively specific sensitivity to the antibiotic or type of antibiotic tested. The latter group can be represented by a set of 20 to 60 strains that can be used for the rapid typing of antibiotics by generating a virtual bar code readout of the specific sensitivities. Taken together, these data reveal the complexity of intrinsic resistance and provide additional targets for the design of codrugs (or combinations of drugs) that potentiate existing antibiotics. PMID:20065048

  4. 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 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

  5. 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

  6. In vitro evaluation of broad-spectrum beta-lactams in the philippines medical centers: role of fourth-generation cephalosporins. The Philippines Antimicrobial Resistance Study Group.

    PubMed

    Johnson, D M; Biedenbach, D J; Jones, R N

    1999-12-01

    Cefepime is a potent broad-spectrum "fourth-generation" cephalosporin. The in vitro activity of cefepime was compared to that of cefpirome, ceftazidime, ceftriaxone, imipenem, and piperacillin/tazobactam in a multilaboratory (nine medical centers) Philippine surveillance project from March through October 1998. A total of 626 Gram-positive and Gram-negative organisms (10 species groups) were tested by the Etest method (AB BIODISK, Solna, Sweden) with results validated by current quality control strain analysis. The overall rank order of usable spectrum of activity was imipenem (4.2% resistance), cefepime (4.5%), cefpirome (5.0%), piperacillin/tazobactam (5.8%) > ceftriaxone (11.2%) > ceftazidime (15.3%), and results did not differ significantly between medical centers. Ceftazidime-resistant Escherichia coli and Klebsiella spp. occurred at rates of 13.3% and 31.1%, respectively, indicating extended-spectrum beta-lactamase (ESBL) activity. Imipenem (100% susceptible), cefepime, and cefpirome (both > or = 97.8% susceptible) were active in vitro against these ESBL phenotypes. Organisms with ceftazidime and/or ceftriaxone-resistant profiles consistent for hyper-production of Amp C cephalosporinases were detected at high rates among the Citrobacter spp. (29.2%) and Enterobacter spp. (45.8%); however, imipenem (100.0% susceptible) and cefepime (98.9%) remained active. Cefepime and imipenem (both 87.5% susceptible) were the most active agents tested against Acinetobacter spp. whereas piperacillin/tazobactam was most effective against P. aeruginosa (80.0% susceptible). Most tested beta-lactams (except ceftazidime) were active versus oxacillin-susceptible staphylococci. These data should be used as a guide for treatment selection with beta-lactam compounds in the Philippines and to serve as a resistance benchmark in comparisons with future studies in this nation. PMID:10668588

  7. Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics.

    PubMed

    Pritsos, C A; Sartorelli, A C

    1986-07-01

    Mitomycin C (MC) is a naturally occurring anticancer agent which has been shown to be more cytotoxic to hypoxic tumor cells than to their aerobic counterparts. The mechanism of action of this agent is thought to involve biological reductive activation, to a species that alkylates DNA. A comparison of the cytotoxicity of MC to EMT6 tumor cells with that of the structural analogues porfiromycin (PM), N-(N',N'-dimethylaminomethylene)amine analogue of mitomycin C (BMY-25282), and N-(N',N'-dimethylaminomethylene)amine analogue of porfiromycin (BL-6783) has demonstrated that PM is considerably less cytotoxic to aerobic EMT6 cells than MC, whereas BMY-25282 and BL-6783 are significantly more toxic. The relative abilities of each of these compounds to generate oxygen free radicals following biological activation were measured. Tumor cell sonicates, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, xanthine oxidase, and mitochondria were used as the biological reducing systems. All four mitomycin antibiotics produced oxygen radicals following biological reduction, a process that may account for the aerobic cytotoxicity of agents of this class. The generation of relative amounts of superoxide and hydroxyl radical were also measured in EMT6 cell sonicates. BMY-25282 and BL-6783 produced significantly greater quantities of oxygen free radicals with the EMT6 cell sonicate, reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, and mitochondria than did MC and PM. In contrast, BMY-25282 and BL-6783 did not generate detectable levels of free radicals in the presence of xanthine oxidase, whereas this enzyme was capable of generating free radicals with MC and PM as substrates. MC consistently produced greater amounts of free radicals than PM with all of the reducing systems. BMY-25282, BL-6783, and MC all generated hydroxyl radicals, while PM did not appear to form these radicals. The findings indicate that a correlation exists between

  8. 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

  9. Biogas generation in anaerobic wastewater treatment under tetracycline antibiotic pressure

    PubMed Central

    Lu, Meiqing; Niu, Xiaojun; Liu, Wei; Zhang, Jun; Wang, Jie; Yang, Jia; Wang, Wenqi; Yang, Zhiquan

    2016-01-01

    The effect of tetracycline (TC) antibiotic on biogas generation in anaerobic wastewater treatment was studied. A lab-scale Anaerobic Baffled Reactor (ABR) with three compartments was used. The reactor was operated with synthetic wastewater in the absence of TC and in the presence of 250 μg/L TC for 90 days, respectively. The removal rate of TC, volatile fatty acids (VFAs), biogas compositions (hydrogen (H2), methane (CH4), carbon dioxide (CO2)), and total biogas production in each compartment were monitored in the two operational conditions. Results showed that the removal rate of TC was 14.97–67.97% in the reactor. The presence of TC had a large negative effect on CH4 and CO2 generation, but appeared to have a positive effect on H2 production and VFAs accumulation. This response indicated that the methanogenesis process was sensitive to TC presence, but the acidogenesis process was insensitive. This suggested that the presence of TC had less influence on the degradation of organic matter but had a strong influence on biogas generation. Additionally, the decrease of CH4 and CO2 generation and the increase of H2 and VFAs accumulation suggest a promising strategy to help alleviate global warming and improve resource recovery in an environmentally friendly approach. PMID:27341657

  10. Biogas generation in anaerobic wastewater treatment under tetracycline antibiotic pressure.

    PubMed

    Lu, Meiqing; Niu, Xiaojun; Liu, Wei; Zhang, Jun; Wang, Jie; Yang, Jia; Wang, Wenqi; Yang, Zhiquan

    2016-01-01

    The effect of tetracycline (TC) antibiotic on biogas generation in anaerobic wastewater treatment was studied. A lab-scale Anaerobic Baffled Reactor (ABR) with three compartments was used. The reactor was operated with synthetic wastewater in the absence of TC and in the presence of 250 μg/L TC for 90 days, respectively. The removal rate of TC, volatile fatty acids (VFAs), biogas compositions (hydrogen (H2), methane (CH4), carbon dioxide (CO2)), and total biogas production in each compartment were monitored in the two operational conditions. Results showed that the removal rate of TC was 14.97-67.97% in the reactor. The presence of TC had a large negative effect on CH4 and CO2 generation, but appeared to have a positive effect on H2 production and VFAs accumulation. This response indicated that the methanogenesis process was sensitive to TC presence, but the acidogenesis process was insensitive. This suggested that the presence of TC had less influence on the degradation of organic matter but had a strong influence on biogas generation. Additionally, the decrease of CH4 and CO2 generation and the increase of H2 and VFAs accumulation suggest a promising strategy to help alleviate global warming and improve resource recovery in an environmentally friendly approach. PMID:27341657

  11. Biogas generation in anaerobic wastewater treatment under tetracycline antibiotic pressure

    NASA Astrophysics Data System (ADS)

    Lu, Meiqing; Niu, Xiaojun; Liu, Wei; Zhang, Jun; Wang, Jie; Yang, Jia; Wang, Wenqi; Yang, Zhiquan

    2016-06-01

    The effect of tetracycline (TC) antibiotic on biogas generation in anaerobic wastewater treatment was studied. A lab-scale Anaerobic Baffled Reactor (ABR) with three compartments was used. The reactor was operated with synthetic wastewater in the absence of TC and in the presence of 250 μg/L TC for 90 days, respectively. The removal rate of TC, volatile fatty acids (VFAs), biogas compositions (hydrogen (H2), methane (CH4), carbon dioxide (CO2)), and total biogas production in each compartment were monitored in the two operational conditions. Results showed that the removal rate of TC was 14.97–67.97% in the reactor. The presence of TC had a large negative effect on CH4 and CO2 generation, but appeared to have a positive effect on H2 production and VFAs accumulation. This response indicated that the methanogenesis process was sensitive to TC presence, but the acidogenesis process was insensitive. This suggested that the presence of TC had less influence on the degradation of organic matter but had a strong influence on biogas generation. Additionally, the decrease of CH4 and CO2 generation and the increase of H2 and VFAs accumulation suggest a promising strategy to help alleviate global warming and improve resource recovery in an environmentally friendly approach.

  12. 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

  13. [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

  14. Ceftobiprole: a new broad spectrum cephalosporin.

    PubMed

    El Solh, Ali

    2009-07-01

    Ceftobiprole, formerly designated BAL9141/Ro 63-9141, is a pyrrolidinone-3-ylidene-methyl cephalosporin with demonstrated in vitro activity against MRSA, Enterococcus faecalis, Enterobacteriaceae and Pseudomonas aeruginosa. Ceftobiprole has a low potential for inducing chromosomal AmpC beta-lactamases but it is hydrolyzed by most extended spectrum beta-lactamases and metallo-beta-lactamases. Glomerular filtration is predominantly responsible for removal of the free drug from the systemic circulation. The efficacy of ceftobiprole in the treatment of complicated skin and ski-structure infections has been recently demonstrated in two Phase III randomized clinical trials involving 1600 patients. Two other Phase III clinical trials to assess ceftobiprole's efficacy in community-acquired pneumonia and nosocomial pneumonia have also concluded. While the drug met the noninferiority criteria for community-acquired pneumonia and nosocomial pneumonia involving non-ventilator associated pneumonia, ceftobiprole was less effective than the comparator in ventilator associated pneumonia subjects. Ceftobiprole was well tolerated with a safety profile consistent with the cephalosporin class of antibiotic. The most frequent drug-related adverse event was dysgeusia. Ceftobiprole is intended for use in the hospital for the treatment of infections that frequently involve beta-lactam-resistant Gram-negative and Gram-positive organisms. PMID:19527192

  15. Cephalosporin Induced Disulfiram-Like Reaction: A Retrospective Review of 78 Cases

    PubMed Central

    Ren, Shiyan; Cao, Yuxia; Zhang, Xiuwei; Jiao, Shichen; Qian, Songyi; Liu, Peng

    2014-01-01

    Concomitant ingestion of alcohol and cephalosporin may cause a disulfiram-like reaction; however its fatal outcomes are not commonly known. We retrospectively reviewed 78 patients who had cephalosporin induced disulfiram-like reaction (CIDLR). The patients who had a negative skin test to cephalosporin prior to intravenous antibiotics were included, and those who were allergic to either alcohol or antibiotics were excluded. The average age of 78 patients was 37.8±12.2 (21–60) years. Of the 78 patients, 93.58% of the patients were males, 70.51% of the patients consumed alcohol after use of antibiotics, and 29.49% patients consumed alcohol initially, followed by intravenous antibiotics; however, no significant difference of morbidity was observed in these two groups. All patients were administered antibiotics intravenously. Five of 78 patients (6.41%) developed severe CIDLR too urgently to be rescued successfully. In conclusion, it is important for clinicians to educate patients that no alcohol should be used if one is taking cephalosporin. Also, clinicians should keep in mind that cephalosporin should not be prescribed for any alcoholics. PMID:24670024

  16. Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors.

    PubMed

    Cocozaki, Alexis I; Altman, Roger B; Huang, Jian; Buurman, Ed T; Kazmirski, Steven L; Doig, Peter; Prince, D Bryan; Blanchard, Scott C; Cate, Jamie H D; Ferguson, Andrew D

    2016-07-19

    Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future. PMID:27382179

  17. Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors

    PubMed Central

    Cocozaki, Alexis I.; Altman, Roger B.; Huang, Jian; Buurman, Ed T.; Kazmirski, Steven L.; Doig, Peter; Prince, D. Bryan; Blanchard, Scott C.; Cate, Jamie H. D.; Ferguson, Andrew D.

    2016-01-01

    Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future. PMID:27382179

  18. 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

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

    PubMed

    Horcajada, Juan Pablo; Cantón, 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 β-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

  20. [Antibacterial activity and beta-lactamase stability of eleven oral cephalosporins].

    PubMed

    Bauernfeind, A; Jungwirth, R; Schweighart, S; Theopold, M

    1990-01-01

    Oral cephalosporins (cefixime, cefdinir, cefetamet, ceftibuten, cefpodoxime, loracarbef, cefprozil, cefuroxime, cefaclor, cefadroxil and BAY 3522) were compared by their antibacterial profile including stability against new beta-lactamases. Both activity and antibacterial spectrum of compounds structurally related to third generation parenteral cephalosporins (of the oximino class) were superior to established compounds. Activity against staphylococci was found to be highest for cefdinir, cefprozil and BAY 3522. Cefetamet, ceftibuten and cefixime demonstrate no clinically meaningful antistaphylococcal activity while the other compounds investigated demonstrate intermediate activity. The antibacterial spectrum was broadest for cefdinir and cefpodoxime. New oral cephalosporins are equally inactive as established compounds against Enterobacter spp., Morganella, Listeria, Pseudomonas and Acinetobacter spp., methicillin-resistant staphylococci, Enterococcus spp., penicillin-resistant pneumococci and anaerobes. New extended broad-spectrum betalactamases (TEM-3, TEM-5, TEM-6, TEM-7, SHV-2, SHV-3, SHV-4, SHV-5, CMY-1, CMY-2, and CTX-M) are active against the majority of oral cephalosporins. Ceftibuten, cefetamet, cefixime and cefdinir were stable against some of these enzymes even to a higher extent than parenteral cephalosporins. New oral cephalosporins should improve the therapeutic perspectives of oral cephalosporins due to their higher activity against pathogens marginally susceptible to established compounds (higher multiplicity of maximum plasma concentrations over MICs of the pathogens) and furthermore by including in their spectrum organisms resistant to established absorbable cephalosporins (e.g. Proteus spp., Providencia spp., Citrobacter spp., and Serratia spp.). PMID:2079378

  1. 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

  2. Optimization of separation and migration behavior of cephalosporins in capillary zone electrophoresis.

    PubMed

    Lin, C E; Chen, H W; Lin, E C; Lin, K S; Huang, H C

    2000-05-26

    The influences of buffer pH, buffer concentration and buffer electrolyte on the migration behavior and separation of 12 cephalosporin antibiotics in capillary zone electrophoresis using three different types of buffer electrolyte, including phosphate, citrate, and 2-(N-morpholino)ethanesulfonate (MES), were investigated. The results indicate that, although buffer pH is a crucial parameter, buffer concentration also plays an important role in the separation of cephalosporins, particularly when cefuroxime and cefazolin, cephalexin and cefaclor, or cefotaxime and cephapirin are present as analytes at the same time. The electrophoretic mobility of cephalosporins and electroosmotic mobility measured in citrate and MES buffers are remarkably different from those measured in phosphate buffer. With citrate buffer, optimum buffer concentration is confined to a small range (35-40 mM), whereas buffer concentrations up to 300 mM can be used with MES buffer. Complete separations of 12 cephalosporins could be satisfactorily achieved with these three buffers under various optimum conditions. However, the separability of 12 cephalosporins with citrate or MES buffer is better than that with phosphate buffer. As a consequence of a greater electrophoretic mobility of cephalosporins than the electroosmotic mobility with citrate buffer at pH below about 5, some cephalosporins are not detectable. The cloudiness of the peak identification and of the magnitudes of the electrophoretic mobility of cefotaxime and cefuroxime reported previously are clarified. In addition, the pKa values of cephradine, cephalexin, cefaclor, and cephapirin attributed to the deprotonation of either an amino group or a pyridinium group are reported, and the migration behavior of these cephalosporins in the pH range studied is quantitatively described. PMID:10893036

  3. 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

  4. Ocular pharmacokinetics of cephalosporins using microdialysis.

    PubMed

    Macha, S; Mitra, A K

    2001-10-01

    The purpose of this study was to delineate the ocular pharmacokinetics of cephalosporins and investigate the presence of peptide transporters in the retina. New Zealand albino rabbits were kept under anesthesia. A concentric microdialysis probe was implanted in the vitreous chamber and linear probe across the cornea in the aqueous humor. Isotonic phosphate buffer saline was perfused through the probes, and samples were collected every 20 min over a period of 10 hr. A 500 microg dose of cephalexin, cephazolin, and cephalothin was administered intravitreally. Inhibition experiments were carried out in vivo, using gly-pro and gly-sar. The vitreal half-lives of cephalexin, cefazolin, and cephalothin were 185.38 +/- 27.25 min, 111.40 +/- 17.17 min, and 146.68 +/- 47.52 min, respectively. Cephalexin generated higher aqueous humor concentrations compared to cefazolin. The pharmacokinetic parameters of cephalexin in the presence of gly-pro, i.e., AUC (44452.06 +/- 3326.55 microg x min/ml), clearance (0.0013 +/- 0.0004 ml/min) and vitreal half-life (825.12 +/- 499.95 min) were different from that of the control (14612.83 +/- 4036.47 microg x min/ml, 0.0036 +/- 0.0011 ml/min, and 187.96 +/- 65.12 min, respectively). Gly-pro did not inhibit cefazolin, and gly-sar showed no effect on the pharmacokinetics of both drugs. These studies indicate the involvement of a peptide carrier in the transport of cephalosporins across the retina. Although gly-pro inhibited the elimination of cephalexin from the vitreous, the effect of an alpha-amino group on peptide carriers was not clearly evident. PMID:11765153

  5. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions, 2009.

    PubMed

    2011-03-01

    Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. From 2007, the Gonococcal Antimicrobial Surveillance Programme (GASP) has been enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres in the WPR. Approximately 8,704 isolates of N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea, incorporating External Quality Assurance controlled methods, from reporting centres in 21 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR. In contrast, from the Pacific Island states Fiji reported low penicillin and quinolone resistance, New Caledonia again reported no penicillin resistance and little quinolone resistance, Tonga reported no penicillin resistance and there was a continued absence of quinolone resistance reported in Papua New Guinea in 2009. The proportion of gonococci reported as 'decreased susceptibility' and 'resistant' to the third-generation cephalosporin antibiotic ceftriaxone varied widely but no major changes were evident in cephalosporin minimum inhibitory concentrations (MIC) patterns in 2009. Altered cephalosporin susceptibility has been associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit high-level plasmid mediated resistance to tetracyclines. The continuing emergence and

  6. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian regions, 2007-2008.

    PubMed

    Tapsall, J W; Limnios, E A; Abu Bakar, Hjh Mahani Hj; Darussalam, Brunei; Ping, Yin Yue; Buadromo, E M; Kumar, P; Singh, S; Lo, J; Bala, M; Risbud, A; Deguchi, T; Tanaka, M; Watanabe, Y; Lee, K; Chong, Y; Noikaseumsy, S; Phouthavane, T; Sam, I-Ching; Tundev, O; Lwin, K M; Eh, P H; Goarant, C; Goursaud, R; Bathgate, T; Brokenshire, M; Latorre, L; Velemu, E; Carlos, C; Leano, S; Telan, E O; Goh, S S; Koh, S T; Ngan, C; Tan, A L; Mananwatte, S; Piyanoot, N; Lokpichat, S; Sirivongranson, P; Fakahau, M; Sitanilei, H; Hung, Le Van

    2010-03-01

    Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. In 2007 and 2008, this Gonococcal Antimicrobial Surveillance Programme (GASP) was enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres within the WPR. Approximately 17,450 N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by external quality controlled methods in 24 reporting centres in 20 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. The proportion of gonococci reported as 'resistant', 'less susceptible' or 'non-susceptible' gonococci to the third-generation cephalosporin antibiotic ceftriaxone lay in a wide range, but no major changes were evident in cephalosporin minimal inhibitory concentration (MIC) patterns in 2007-2008. Altered cephalosporin susceptibility was associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit a form of plasmid mediated high level resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR supports the need for gonococcal antimicrobial resistance surveillance programs such as GASP to be

  7. Second-Generation Phenylthiazole Antibiotics with Enhanced Pharmacokinetic Properties.

    PubMed

    Seleem, Mohammed A; Disouky, Ahmed M; Mohammad, Haroon; Abdelghany, Tamer M; Mancy, Ahmed S; Bayoumi, Sammar A; Elshafeey, Ahmed; El-Morsy, Ahmed; Seleem, Mohamed N; Mayhoub, Abdelrahman S

    2016-05-26

    A series of second-generation analogues for 2-(1-(2-(4-butylphenyl)-4-methylthiazol-5-yl)ethylidene)aminoguanidine (1) have been synthesized and tested against methicillin-resistant Staphylococcus aureus (MRSA). The compounds were designed with the objective of improving pharmacokinetic properties. This main aim has been accomplished by replacing the rapidly hydrolyzable Schiff-base moiety of first-generation members with a cyclic, unhydrolyzable pyrimidine ring. The hydrazide-containing analogue 17 was identified as the most potent analogue constructed thus far. The corresponding amine 8 was 8 times less active. Finally, incorporating the nitrogenous side chain within an aromatic system completely abolished the antibacterial character. Replacement of the n-butyl group with cyclic bioisosteres revealed cyclohexenyl analogue 29, which showed significant improvement in in vitro anti-MRSA potency. Increasing or decreasing the ring size deteriorated the antibacterial activity. Compound 17 demonstrated a superior in vitro and in vivo pharmacokinetic profile, providing compelling evidence that this particular analogue is a good drug candidate worthy of further analysis. PMID:27187739

  8. In Vitro selection of Neisseria gonorrhoeae mutants with elevated MIC values and increased resistance to cephalosporins.

    PubMed

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

    2014-11-01

    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

  9. 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

  10. New Dimensions of Research on Actinomycetes: Quest for Next Generation Antibiotics.

    PubMed

    Jose, Polpass Arul; Jha, Bhavanath

    2016-01-01

    Starting with the discovery of streptomycin, the promise of natural products research on actinomycetes has been captivating researchers and offered an array of life-saving antibiotics. However, most of the actinomycetes have received a little attention of researchers beyond isolation and activity screening. Noticeable gaps in genomic information and associated biosynthetic potential of actinomycetes are mainly the reasons for this situation, which has led to a decline in the discovery rate of novel antibiotics. Recent insights gained from genome mining have revealed a massive existence of previously unrecognized biosynthetic potential in actinomycetes. Successive developments in next-generation sequencing, genome editing, analytical separation and high-resolution spectroscopic methods have reinvigorated interest on such actinomycetes and opened new avenues for the discovery of natural and natural-inspired antibiotics. This article describes the new dimensions that have driven the ongoing resurgence of research on actinomycetes with historical background since the commencement in 1940, for the attention of worldwide researchers. Coupled with increasing advancement in molecular and analytical tools and techniques, the discovery of next-generation antibiotics could be possible by revisiting the untapped potential of actinomycetes from different natural sources. PMID:27594853

  11. New Dimensions of Research on Actinomycetes: Quest for Next Generation Antibiotics

    PubMed Central

    Jose, Polpass Arul; Jha, Bhavanath

    2016-01-01

    Starting with the discovery of streptomycin, the promise of natural products research on actinomycetes has been captivating researchers and offered an array of life-saving antibiotics. However, most of the actinomycetes have received a little attention of researchers beyond isolation and activity screening. Noticeable gaps in genomic information and associated biosynthetic potential of actinomycetes are mainly the reasons for this situation, which has led to a decline in the discovery rate of novel antibiotics. Recent insights gained from genome mining have revealed a massive existence of previously unrecognized biosynthetic potential in actinomycetes. Successive developments in next-generation sequencing, genome editing, analytical separation and high-resolution spectroscopic methods have reinvigorated interest on such actinomycetes and opened new avenues for the discovery of natural and natural-inspired antibiotics. This article describes the new dimensions that have driven the ongoing resurgence of research on actinomycetes with historical background since the commencement in 1940, for the attention of worldwide researchers. Coupled with increasing advancement in molecular and analytical tools and techniques, the discovery of next-generation antibiotics could be possible by revisiting the untapped potential of actinomycetes from different natural sources. PMID:27594853

  12. Antibiotic-induced diarrhea.

    PubMed

    Vogel, L C

    1995-01-01

    Diarrhea is a common complication of antibiotic therapy and can range from mild soiling of a cast to severe and life-threatening pseudomembranous colitis. Although clindamycin is the most notorious, almost all antibiotics, particularly penicillins and cephalosporins, may also be responsible (Bartlett, 1992; Kelly, Pothoulakis, & LaMont, 1994). Because of the frequent use of these antibiotics in orthopaedic patients, antibiotic-associated enteric disease is a common problem in this population. About 15% to 25% of cases of antibiotic-associated diarrhea are caused by Clostridium difficile (Bartlett, 1992; George, 1984; Kelly et al., 1994). The majority of patients with antibiotic-associated diarrhea have no identifiable etiologic agent. Salmonella, enterotoxin-producing Clostridium perfringens (Borriello et al., 1984) and Candida albicans (Danna et al., 1991) have rarely been identified as causative agents. This article describes the role of C. difficile as an enteric pathogen and its spectrum of clinical disease, including diagnosis, treatment, and prevention of nosocomial transmission. PMID:7761131

  13. 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

  14. Kinetic spectrophotometric determination of certain cephalosporins in pharmaceutical formulations.

    PubMed

    Omar, Mahmoud A; Abdelmageed, Osama H; Attia, Tamer Z

    2009-01-01

    A simple, reliable, and sensitive kinetic spectrophotometric method was developed for determination of eight cephalosporin antibiotics, namely, Cefotaxime sodium, Cephapirin sodium, Cephradine dihydrate, Cephalexin monohydrate, Ceftazidime pentahydrate, Cefazoline sodium, Ceftriaxone sodium, and Cefuroxime sodium. The method depends on oxidation of each of studied drugs with alkaline potassium permanganate. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 610 nm. The initial rate and fixed time (at 3 minutes) methods are utilized for construction of calibration graphs to determine the concentration of the studied drugs. The calibration graphs are linear in the concentration ranges 5-15 mug mL(-1) and 5-25 mug mL(-1) using the initial rate and fixed time methods, respectively. The results are validated statistically and checked through recovery studies. The method has been successfully applied for the determination of the studied cephalosporins in commercial dosage forms. Statistical comparisons of the results with the reference methods show the excellent agreement and indicate no significant difference in accuracy and precision. PMID:20140078

  15. β-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 β-lactam-containing penicillins, cephalosporins and nocardicins. Although penicillins and cephalosporins are synthesised from a classically derived NRPS tripeptide (from ACVS, δ-(L-α-aminoadipyl)–L-cysteinyl–D-valine synthetase)2, we now report an unprecedented NRPS activity to both assemble a serine-containing peptide and mediate its cyclisation to the critical β-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 β-lactam antibiotic families: penicillin/cephalosporins, clavams and carbapenems. These findings raise the possibility that β-lactam rings can be regio- and stereospecifically integrated into engineered peptides for application as, for example, targeted protease inactivators.3,4 PMID:25624104

  16. Bacterial proteinases as targets for the development of second-generation antibiotics.

    PubMed

    Travis, J; Potempa, J

    2000-03-01

    The emergence of bacterial pathogen resistance to common antibiotics strongly supports the necessity to develop alternative mechanisms for combating drug-resistant forms of these infective organisms. Currently, few pharmaceutical companies have attempted to investigate the possibility of interrupting metabolic pathways other than those that are known to be involved in cell wall biosynthesis. In this review, we describe multiple, novel roles for bacterial proteinases during infection using, as a specific example, the enzymes from the organism Porphyromonas gingivalis, a periodontopathogen, which is known to be involved in the development and progression of periodontal disease. In this manner, we are able to justify the concept of developing synthetic inhibitors against members of this class of enzymes as potential second-generation antibiotics. Such compounds could not only prove valuable in retarding the growth and proliferation of bacterial pathogens but also lead to the use of this class of inhibitors against invasion by other infective organisms. PMID:10708847

  17. Susceptibility of Pseudomonas aeruginosa to catechol-substituted cephalosporin is unrelated to the pyochelin-Fe transporter FptA.

    PubMed

    Hoegy, Françoise; Gwynn, Michael N; Schalk, Isabelle J

    2010-05-01

    Previously it has been postulated that the pyochelin-Fe outer membrane transporter, FptA, is involved in the uptake of catechol-substituted cephalosporins in Pseudomonas aeruginosa. Iron uptake and antibacterial activity studies on different mutants showed clearly that FptA is unable to bind and transport these antibiotics. PMID:19777323

  18. A chromogenic cephalosporin for β-lactamase inhibitor screening assays.

    PubMed

    Yu, Sophia; Vosbeek, Amy; Corbella, Katherine; Severson, Jonathan; Schesser, Jacob; Sutton, Larry D

    2012-09-15

    Production of β-lactamases is the primary mechanism of antibiotic resistance employed by gram-negative pathogens. Chromogenic β-lactams are important reagents for detection and assay of β-lactamases, but limited commercial availability and exorbitant pricing of these compounds are prohibitive. Here we describe a straightforward synthesis of a chromogenic cephalosporin for β-lactamase assay that gives an overall yield of 74%. On hydrolysis, its λ(max) undergoes a bathochromic shift that is easy to see and measure spectrophotometrically with a Δε(442 nm) of 14,500 cm⁻¹ M⁻¹. This compound was shown to be a substrate for a variety of β-lactamases. PMID:22709853

  19. Draft Genome Sequence of Escherichia coli Strain VKPM B-10182, Producing the Enzyme for Synthesis of Cephalosporin Acids

    PubMed Central

    Mardanov, Andrey V.; Eldarov, Mikhail A.; Sklyarenko, Anna V.; Dumina, Maria V.; Beletsky, Alexey V.; Yarotsky, Sergey V.

    2014-01-01

    Escherichia coli strain VKPM B-10182, obtained by chemical mutagenesis from E. coli strain ATCC 9637, produces cephalosporin acid synthetase employed in the synthesis of β-lactam antibiotics, such as cefazolin. The draft genome sequence of strain VKPM B-10182 revealed 32 indels and 1,780 point mutations that might account for the improvement in antibiotic synthesis that we observed. PMID:25414512

  20. Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

    PubMed Central

    Elsayed, Mossad Gamaleddin Ahmed; Elkomy, Ashraf Abdelhakim Ahmed; Gaballah, Mahmoud Salem; Elbadawy, Mohamed

    2014-01-01

    Objectives: To investigate the nephrotoxic effect and biochemical alterations induced by cefepime in rats. Materials and Methods: Cefepime was administered intramuscularly at doses of 45, 90 and 180 mg/kg b.wt. once daily for 5 consecutive days. The serum and urine samples were used for quantitative determination of urea, creatinine, glucose, total protein, calcium, sodium and potassium. The histopathological examination of kidney tissues was performed 1, 4 and 8 days after the last dose of cefepime administration. Results: Cefepime induced a significant increase in the total amount of urine per day, urea and creatinine concentration in the serum and urine and significant decrease in their clearance. Cefepime also caused a significant gluocosuria and proteinuria and significant decrease in their serum concentrations. The effect of cefepime on serum and urine concentrations of calcium, sodium and potassium were also determined. Cefepime injection in the three tested doses caused renal tubular, glomerular and vascular changes. The severity of these changes was dose dependent. In conclusion, these results suggest a possible contribution of cefepime in the nephrotoxicity and biochemical alterations, especially at high doses. Therefore, the renal functions should be monitored during the cefepime therapy. PMID:24554908

  1. Azithromycin resistance is coevolving with reduced susceptibility to cephalosporins in Neisseria gonorrhoeae in Ontario, Canada.

    PubMed

    Allen, Vanessa G; Seah, Christine; Martin, Irene; Melano, Roberto G

    2014-05-01

    Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZM(r)) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZM(r) isolates in Ontario, Canada. Nineteen AZM(r) clinical isolates (one per patient; MIC, ≥2 μg/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZM(r) level; group A isolates displayed high-level resistance (MIC, ≥2,048 μg/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 μg/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n = 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 μg/ml, PBP2 pattern XXXIV). This AZM(r) phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 μg/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, ≤0.031 μg/ml), increasing the chances of additional selection of AZM(r) mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea. PMID:24514092

  2. Not All Antibiotic Use Practices in Food-Animal Agriculture Afford the Same Risk.

    PubMed

    Subbiah, Murugan; Mitchell, Shannon M; Call, Douglas R

    2016-03-01

    The World Health Organization has identified quinolones, third- and fourth-generation cephalosporins, and macrolides as the most important antibiotics in human medicine. In the context of agricultural use of antibiotics, the principle zoonotic agents of concern are , spp., , and spp. Antibiotic exposure provides a selective advantage to resistant strains of these bacteria relative to their susceptible conspecifics. This is a dose-dependent process, and consequently antibiotic use practices that involve higher doses will exert greater and longer-lasting selective pressure in favor of resistant bacterial populations and will therefore increase the probability of transmission to people and other animals. Oral administration has a greater impact on enteric flora with the exception of fluoroquinolone treatments, which appear to affect the enteric flora equally if administered orally or parenterally. The use of quinolones in agriculture deserves heightened scrutiny because of the ease with which these broad-spectrum antibiotics favor spontaneously resistant bacteria in exposed populations. When present at sufficient concentrations, excreted antibiotics have the potential to selectively favor resistant bacteria in the environment and increase the probability of transmission to people and animals. The bioavailability of antibiotics varies greatly: some antibiotics remain active in soils (florfenicol, β-lactams), whereas others may be rapidly sorbed and thus not bioavailable (tetracycline, macrolides, quinolones). When considering the risks of different antibiotic use practices in agriculture, it would be prudent to focus attention on practices that involve high doses, oral delivery, and residues of antibiotics that remain active in soils. PMID:27065409

  3. Bacteriocins Produced by L. Fermentum and L. Acidophilus Can Inhibit Cephalosporin Resistant E. Coli.

    PubMed Central

    Riaz, Saba; Kashif Nawaz, Syed; Hasnain, Shahida

    2010-01-01

    Reemerging infections occur due to resistant bacteria. Such infections create restrictions for clinicians and microbiologists in drug selection. Such problems demand new strategies for solution. Use of bacteriocins for this purpose may be fruitful. In the present research work, the inhibitory effects of bactericins on cephalosporin resistant Escherichia coli are used as model system for the control of antibiotic resistant pathogenic bacteria. Cephalosporin resistant Escherichia coli strain was isolated from pus by using conventional methodology. For bacteriocin production, Lactobacilli strains were selected by using selective media. Out of seventy two strains isolated from yogurt, fecal materials of human, chick, parrot and cat, only two strains (strain 45 and strain 52) were found to produce bacteriocins having antimicrobial potential against cephalosporin resistant Escherichia coli. Biochemical characterization showed that strain 45 belonged to group of Lactobacillus fermentum and strain 52 to Lactobacillus acidophilus. Both strains showed maximum growth at 25°C and 35°C respectively. Suitable pH was 5.5 and 6.0 for Lactobacillus fermentum and Lactobacillus acidophilus respectively. Bacteriocins produced by both strains were found stable at 50, 75 and 100°C for 60min. Function of bacteriocin was also not disturbed due to change in pH. These findings suggest that bacteriocin produced by Lactobacillus fermentum and Lactobacillus acidophilus can be used for the infection control of cephalosporin resistant Escherichia coli. PMID:24031540

  4. Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.

    PubMed

    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

  5. 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

  6. [Initial antibiotic therapy of neonatal sepsis].

    PubMed

    Jesić, Milos; Jesić, Maja; Maglajlić, Svjetlana; Lukac, Marija; Sindjić, Sanja; Vujović, Dragana; Grković, Slobodanka

    2004-10-01

    It is certain that in the past the types of bacterial agents responsible for neonatal sepsis and their sensitivity to antibiotics were not the same in all historical periods. However, the reports confirming the conclusion have been published only in the last three years. According to these facts, the bacterial causes of neonatal sepsis were analyzed in patients treated at the University children's hospital in Belgrade (S&M) as well as their sensitivity to antibiotics to determine the most effective initial therapy. Between January 2001 and June 2004, 35 neonates, aged from 1-30 days, with positive blood culture were treated. Gram-negative bacteria were the cause of sepsis in 57% of patients (Pseudomonas--20%, Klebsiella--20%, E. coli--8.5%, Acinetobacter--8.5%), gram-positive in 43% (coagulase-negative Staphylococci--14%, Staphylococcus epidermidis--14%, Staphylococcus aureus--9%, Streptococcus group B--3%, Listeria monocytogenes--3%). The bacteria were the most sensitive to carbapenems (85-89%), amikacin (68%), third-generation cephalosporins (47-50%), while the sensitivity to gentamicin was less than expected (48.5%). Sensitivity to ampicillin (8%) confirmed a high level of resistance to this antibiotic. All isolated Staphylococci were sensitive to vancomycin, and the overall methicillin resistance was 46%. Combined cefotaxime and amikacin therapy was the most effective of all suggested initial combinations of antibiotics (74%). The sensitivity to all other combinations of antibiotics was 51-71%. The most adequate initial combination of antibiotics for the treatment of neonatal sepsis is cefotaxime plus amikacin. The most adequate antibiotic for the treatment of nosocomial neonatal sepsis is carbapenem. PMID:15615466

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

    PubMed Central

    Hancu, Gabriel; Sasebeşi, 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

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

    PubMed Central

    Raymond, Frédéric; Ouameur, Amin A; Déraspe, Maxime; Iqbal, Naeem; Gingras, Hélène; Dridi, Bédis; Leprohon, Philippe; Plante, Pier-Luc; Giroux, Richard; Bérubé, Ève; 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

    2016-01-01

    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

  9. Distribution and persistence of cephalosporins in cephalosporin producing wastewater using SPE and UPLC-MS/MS method.

    PubMed

    Yu, Xin; Tang, Xinyao; Zuo, Jiane; Zhang, Mengyu; Chen, Lei; Li, Zaixing

    2016-11-01

    An investigation to study the distribution and persistence of cephalosporins in the cephalosporin producing wastewater was carried out in this paper. The target cephalosporins included ceftriaxone (CRO), cefalexin (CEF), cefotaxime (CTX), cefazolin (CZO), cefuroxime (CXM), cefoxitin (CFX) and cefradine (CF). A rapid and reliable detection method for cephalosporins was established based on solid phase extraction and ultra-performance liquid chromatography - tandem mass spectrometry. In the cephalosporin producing wastewater effluent (CPWWeff), the limit of quantification for the targets ranged from 27.5ng/L to 131.8ng/L, and the recoveries for all of the analytes ranged from 73% to 102%. The mean concentrations of the seven cephalosporins were 12.85-141.55μg/L and 0.05-24.38μg/L in cephalosporin producing wastewater influent and effluent, respectively. Although high removal efficiencies were achieved for the cephalosporins (78.8-99.7%), up to 1.9kg of cephalosporins was discharged per day from the investigated C-WWTP. The degradation processes of CRO, CEF, CZO and CXM followed first-order kinetics in CPWWeff under all of the testing conditions. The degradation rates of tested cephalosporins were accelerated by high temperature and light. Persistence of CXM was the highest among the four tested cephalosporins in CPWWeff. PMID:27328396

  10. [Mechanisms of resistance in Enterobacteriaceae towards beta-lactamase antibiotics].

    PubMed

    Susić, Edita

    2004-01-01

    Except for Salmonella spp., all Enterobacteriaceae produce intrinsic chromosomal encoded beta-lactamases which, beside their physiologic role in cell-wall synthesis and natural beta-lactam protection, are responsible for intrinsic resistance of individual species among Enterobacteriaceae. E. coli and Shigella spp. produce a small amount of AmpC beta-lactamases and are susceptible to ampicillin and other beta-lactam antibiotic agents. Enterobacter spp, C. freundii, Serratia spp., M. morganii, P. stuarti and P. rettgeri produce small amounts of inducible AmpC beta-lactamases which are not inhibited by beta-lactamases inhibitor, causing intrinsic resistance to ampicillin, co-amoxiclav and first-generation cephalosporins. K. pneumoniae produces small amounts of SHV-1 beta-lactamases, and K. oxytoca chromosomal K1 beta-lactamase, causing resistance to ampicillin, carbencillin, ticarcillin and attenuated zone of inhibition to piperacillin, compared to piperacillin with tazobactam. They are susceptible to beta-lactamase inhibitors. Whereas P. mirabilis shows a minor chromosomal expression of beta-lactamases, P. vulgaris produces chromosomal beta-lactamases of class A (cefuroximases), causing resistance to ampicillin, ticarcillin, and first- and second-generation cephalosporins. Antibiotics have caused the appearance of acquired or secondary beta-lactamases, with the sole function of protecting bacteria from antibiotics. The production of broad-spectrum beta-lactamases (TEM-1, TEM-2, SHV-1, OXA-1) results in resistance to ampicillin, ticarcillin, first-generation cephalosporins and piperacillin. A high level of beta-lactamases leads to resistance to their inhibitors. The plasmid-mediated extended-spectrum beta-lactamases (ESBLs) are of increasing concern. Most are mutants of classic TEM- and SHV-beta-lactamases types. Unlike these parent enzymes, ESBLs hydrolyze oxymino-cephalosporins such as cefuroxime, cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefpirome and

  11. Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients.

    PubMed

    Zerr, Danielle M; Miles-Jay, Arianna; Kronman, Matthew P; Zhou, Chuan; Adler, Amanda L; Haaland, Wren; Weissman, Scott J; Elward, Alexis; Newland, Jason G; Zaoutis, Theoklis; Qin, Xuan

    2016-07-01

    The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible. PMID:27139486

  12. 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

  13. 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

  14. In silico analysis of different generation β 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 β-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 β-lactam antibiotics and concluded that the third generation of β-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 β-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis. PMID:25118647

  15. 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.

  16. Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study

    PubMed Central

    Shen, Li-Jiuan; Wu, Fe-Lin Lin; Tsay, Woei; Hung, Chien-Ching; Lin, Shu-Wen

    2016-01-01

    Objective Existing data regarding the risk of hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins are limited by the small sample size. This population-based study aimed to examine the association between exposure to hypoprothrombinemia-inducing cephalosporins and hemorrhagic events using National Health Insurance Research Database in Taiwan. Design A nationwide nested case-control study. Setting National Health Insurance Research database. Participants We conducted a nested case-control study within a cohort of 6191 patients who received hypoprothrombinemia-inducing cephalosporins and other antibiotics for more than 48 hours. Multivariable conditional logistic regressions were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins (overall, cumulative dose measured as defined daily dose (DDD), and individual cephalosporins). Results Within the cohort, we identified 704 patients with hemorrhagic events and 2816 matched controls. Use of hypoprothrombinemia-inducing cephalosporins was associated with increased risk of hemorrhagic events (aOR, 1.71; 95% CI, 1.42–2.06), which increased with higher cumulative doses (<3 DDDs, aOR 1.62; 3–5 DDDs, aOR 1.78; and >5 DDDs, aOR 1.89). The aOR for individual cephalosporin was 2.88 (95% CI, 2.08–4.00), 1.35 (1.09–1.67) and 4.57 (2.63–7.95) for cefmetazole, flomoxef, and cefoperazone, respectively. Other risk factors included use of anticoagulants (aOR 2.08 [95% CI, 1.64–2.63]), liver failure (aOR 1.69 [1.30–2.18]), poor nutritional status (aOR 1.41 [1.15–1.73]), and history of hemorrhagic events (aOR 2.57 [1.94–3.41]) 6 months prior to the index date. Conclusions Use of hypoprothrombinemia-inducing cephalosporins increases risk of hemorrhagic events. Close watch for hemorrhagic events is recommended when prescribing these cephalosporins, especially in

  17. Prophylactic Antibiotic Management of Surgical Patients Noted as "Allergic" to Penicillin at Two Academic Hospitals.

    PubMed

    Epstein, Richard H; Jacques, Paul St; Wanderer, Jonathan P; Bombulie, Mark R; Agarwalla, Niraj

    2016-05-01

    We studied prophylactic antibiotics administered at 2 academic medical centers during a 6-year period where a cephalosporin was indicated but an "allergy" to penicillin was noted. Another drug (typically vancomycin or clindamycin) was substituted approximately 80% of the time; this occurred frequently even when symptoms unrelated to acute hypersensitivity were listed. In >50% of cases, the reaction was either omitted or vague (e.g., simply "rash"). Given the estimated 1% cross-reactivity between penicillins and cephalosporins with similar R1 side chains, many of these patients could have received either the prescribed cephalosporin or another cephalosporin with a different R1 side chain. PMID:26556109

  18. 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

  19. 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

  20. 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, σ(B) , σ(H) , σ(L) and PrfA, of which the most prominent role play LisR, CesR and σ(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

  1. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  2. Simultaneous determination of 22 cephalosporins drug residues in pork muscle using liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Weiqing; Shen, Haiying; Hong, Yunhe; Zhang, Yuan; Yuan, Fei; Zhang, Feng

    2016-06-01

    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 22 common cephalosporins from the first generation to the fourth generation in pork muscle by liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Under the optimized extraction conditions, samples were directly purified through membrane filtration to separate all 22 cephalosporins and the critical pairs of each parent drug were completely separated. Variables affecting the LC-MS/MS were optimized to get a better separation. The excellent selectivity and sensitivity achieved in multiple reactions monitoring (MRM) mode allowed satisfactory confirmation and quantitation for the 22 cephalosporins. The linear range of the 22 cephalosporins is 0.06-100.0μg/L with good correlation coefficients (r(2)>0.9920). The limits of detection (LODs) and limits of quantitation (LOQs) of these compounds were in the range 0.04-3.0μg/L and 0.06-10.0μg/kg, respectively. The average intra-day recoveries at 3 spiked levels (LOQ, 2LOQ, 4LOQ) were all in the range 83.6-113.0% with RSDs (n=6) lower than 6.5%. The method of LC-MS/MS developed in this study was initially applied to the research of 22 cephalosporins in 12 retail pork samples and proved to be accurate, sensitive, minimum sample pre-treatment, convenient and practical. PMID:27131893

  3. Detection of Favorable Oral Cephalosporin-Clavulanate Interactions by In Vitro Disk Approximation Susceptibility Testing of Extended-Spectrum-Beta-Lactamase-Producing Members of the Enterobacteriaceae

    PubMed Central

    Campbell, Jennifer D.; Lewis, James S.; McElmeel, M. Leticia; Fulcher, Letitia C.

    2012-01-01

    Extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacteriaceae are often resistant to multiple drug classes, making therapy of urinary infections with oral antibiotics difficult. Previously it was shown that amoxicillin-clavulanate can provide clavulanate inhibition of ESBLs and protect an oral cephalosporin present in combination when tested by broth microdilution. This study has shown that disk approximation testing could detect favorable cephalosporin-clavulanate interactions among a group of 101 previously characterized members of the Enterobacteriaceae with CTX-M, SHV, or TEM ESBLs. PMID:22170910

  4. 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 V3–V5. 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. PMID:26813799

  5. Antibiotic Prescriptions and Prophylaxis in Italian Children. Is It Time to Change? Data from the ARPEC Project

    PubMed Central

    Montagnani, Carlotta; Lo Vecchio, Andrea; Romanengo, Marta; Tagliabue, Claudia; Centenari, Chiara; D’Argenio, Patrizia; Lundin, Rebecca; Giaquinto, Carlo; Galli, Luisa; Guarino, Alfredo; Esposito, Susanna; Sharland, Mike; Versporten, Ann; Goossens, Herman; Nicolini, Giangiacomo

    2016-01-01

    Background Antimicrobials are the most commonly prescribed drugs. Many studies have evaluated antibiotic prescriptions in the paediatric outpatient but few studies describing the real antibiotic consumption in Italian children’s hospitals have been published. Point-prevalence survey (PPS) has been shown to be a simple, feasible and reliable standardized method for antimicrobials surveillance in children and neonates admitted to the hospital. In this paper, we presented data from a PPS on antimicrobial prescriptions carried out in 7 large Italian paediatric institutions. Methods A 1-day PPS on antibiotic use in hospitalized neonates and children was performed in Italy between October and December 2012 as part of the Antibiotic Resistance and Prescribing in European Children project (ARPEC). Seven institutions in seven Italian cities were involved. The survey included all admitted patients less than 18 years of age present in the ward at 8:00 am on the day of the survey, who had at least one on-going antibiotic prescription. For all patients data about age, weight, underlying disease, antimicrobial agent, dose and indication for treatment were collected. Results The PPS was performed in 61 wards within 7 Italian institutions. A total of 899 patients were eligible and 349 (38.9%) had an on-going prescription for one or more antibiotics, with variable rates among the hospitals (25.7% - 53.8%). We describe antibiotic prescriptions separately in neonates (<30 days old) and children (> = 30 days to <18 years old). In the neonatal cohort, 62.8% received antibiotics for prophylaxis and only 37.2% on those on antibiotics were treated for infection. Penicillins and aminoglycosides were the most prescribed antibiotic classes. In the paediatric cohort, 64.4% of patients were receiving antibiotics for treatment of infections and 35.5% for prophylaxis. Third generation cephalosporins and penicillin plus inhibitors were the top two antibiotic classes. The main reason for

  6. Recent Trends in Outpatient Antibiotic Use in Children

    PubMed Central

    Kleinman, Kenneth P.; Raebel, Marsha A.; Nordin, James D.; Lakoma, Matthew D.; Dutta-Linn, M. Maya; Finkelstein, Jonathan A.

    2014-01-01

    OBJECTIVE: The goal of this study was to determine changes in antibiotic-dispensing rates among children in 3 health plans located in New England [A], the Mountain West [B], and the Midwest [C] regions of the United States. METHODS: Pharmacy and outpatient claims from September 2000 to August 2010 were used to calculate rates of antibiotic dispensing per person-year for children aged 3 months to 18 years. Differences in rates by year, diagnosis, and health plan were tested by using Poisson regression. The data were analyzed to determine whether there was a change in the rate of decline over time. RESULTS: Antibiotic use in the 3- to <24-month age group varied at baseline according to health plan (A: 2.27, B: 1.40, C: 2.23 antibiotics per person-year; P < .001). The downward trend in antibiotic dispensing slowed, stabilized, or reversed during this 10-year period. In the 3- to <24-month age group, we observed 5.0%, 9.3%, and 7.2% annual declines early in the decade in the 3 plans, respectively. These dropped to 2.4%, 2.1%, and 0.5% annual declines by the end of the decade. Third-generation cephalosporin use for otitis media increased 1.6-, 15-, and 5.5-fold in plans A, B, and C in young children. Similar attenuation of decline in antibiotic use and increases in use of broad-spectrum agents were seen in other age groups. CONCLUSIONS: Antibiotic dispensing for children may have reached a new plateau. Along with identifying best practices in low-prescribing areas, decreasing broad-spectrum use for particular conditions should be a continuing focus of intervention efforts. PMID:24488744

  7. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis.

    PubMed

    Gold, Ben; Smith, Robert; Nguyen, Quyen; Roberts, Julia; Ling, Yan; Lopez Quezada, Landys; Somersan, Selin; Warrier, Thulasi; Little, David; Pingle, Maneesh; Zhang, David; Ballinger, Elaine; Zimmerman, Matthew; Dartois, Véronique; Hanson, Paul; Mitscher, Lester A; Porubsky, Patrick; Rogers, Steven; Schoenen, Frank J; Nathan, Carl; Aubé, Jeffrey

    2016-07-14

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells. PMID:27144688

  8. Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    2016-01-01

    We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a β-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity to the macrophages or other mammalian cells. PMID:27144688

  9. Efficacy of cryptdin-2 as an adjunct to antibiotics from various generations against salmonella.

    PubMed

    Singh, Aman Preet; Prabha, Vijay; Rishi, Praveen

    2014-09-01

    Emerging drug resistance in Salmonella coupled with the recent poor success rate of antibiotic discovery programs of the pharmaceutical industry is a cause for significant concern. It has forced the scientific community to look for alternative new classes of antimicrobial compounds. In this context, combinations of antimicrobial peptides (AMPs) and conventional antibiotics have gained interest owing to their versatile applications. The present study was therefore planned to evaluate the synergistic effects, if any, of cryptdin-2, a mouse Paneth cell alpha-defensin, in combination with four different antibiotics i.e. ciprofloxacin, ceftriaxone, cefotaxime and chloramphenicol, which are conventionally used against Salmonella. Minimum bactericidal concentrations of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by fractional bactericidal concentration index (checkerboard test) and time-kill assay. Cryptdin-2-ciprofloxacin, cryptdin-2-ceftriaxone and cryptdin-2-cefotaxime combinations were found synergistic as evident by in vitro assays. This synergism provides an additional therapeutic choice by allowing the use of conventional antibiotics in conjunction with AMPs against MDR Salmonella. PMID:24891740

  10. Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections

    PubMed Central

    Hidalgo, Jose A; Vinluan, Celeste M; Antony, Nishaal

    2016-01-01

    There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz®, the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations. PMID:27528799

  11. Ceftazidime/avibactam: a novel cephalosporin/nonbeta-lactam beta-lactamase inhibitor for the treatment of complicated urinary tract infections and complicated intra-abdominal infections.

    PubMed

    Hidalgo, Jose A; Vinluan, Celeste M; Antony, Nishaal

    2016-01-01

    There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz(®), the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations. PMID:27528799

  12. Cephalosporin-induced alteration in hepatic glutathione redox state. A potential mechanism for inhibition of hepatic reduction of vitamin K1,2,3-epoxide in the rat.

    PubMed Central

    Mitchell, M C; Mallat, A; Lipsky, J J

    1990-01-01

    Hypoprothrombinemia is a serious adverse effect of antimicrobial therapy that occurs after administration of some second- and third-generation cephalosporins which contain the methyltetrazole-thiol (MTT) group. Previous studies have shown that in vitro MTT directly inhibits microsomal gamma-carboxylation of a synthetic pentapeptide. Since MTT is a thiocarbamide, a type of compound that can increase oxidation of glutathione, the present studies were carried out to determine whether alterations in hepatic glutathione redox state might interfere with vitamin K metabolism. Dose-related increases in biliary efflux and hepatic concentration of oxidized glutathione (GSSG) occurred after intravenous administration of MTT or MTT-containing antibiotics to rats. This finding suggested that these compounds could alter the hepatic glutathione redox state in vivo. Microsomal reduction of vitamin K epoxide occurred in the presence of 100 microM dithiothreitol (DTT), but was inhibited by preincubation with GSSG at concentrations as low as 10 microM. At higher concentrations of DTT (1.0 mM) inhibition by GSSG persisted, but higher concentrations were required, suggesting that the thiol/disulfide ratio, rather than the absolute concentration of GSSG was important. By contrast, GSSG did not effect microsomal gamma-carboxylation of a pentapeptide, using either vitamin K1 or its hydroquinone as a cofactor. These findings suggest a novel mechanism for the hypoprothrombinemia occurring after administration of MTT-containing antibiotics. PMID:1978724

  13. Antibiogram of Salmonella Isolates: Time to Consider Antibiotic Salvage

    PubMed Central

    Hemavathi; Dayanand, DK; Shenoy, Poornima; Sarmah, Pooja

    2016-01-01

    Introduction Enteric fever is a major problem especially in developing countries. Timely and appropriate treatment plays a very important role in reducing the mortality. Fluoroquinolones and cephalosporins are the treatment options for enteric fever. Recent studies have shown that it is time to reconsider the use of earlier antibiotics. Aim The study was aimed to know whether salvage is possible and to avoid treatment failures following fluoroquinolone usage. Materials and Methods A one year retrospective data of Salmonella species isolated from 319 blood samples from our hospital and other diagnostic centers were studied. Demographic data, organism isolated and their changing pattern of antibiogram were analysed. Results Out of 319 Salmonella isolates, 52.4% (167) was Salmonella typhi (S. typhi) and 47.6% (152) Salmonella paratyphi A (S. paratyphi A), with a male preponderance. Most of the salmonellae were isolated in the months of June and July, with the majority being in the 1-10 and 21-30 years age groups. Both species were highly susceptible to chloramphenicol (95.2% and 100%) followed by third generation cephalosporins (97% and 98%), cotrimoxazole (95.8% and 98.6%) and ampicillin (94.6% and 93.4%) respectively. Highest resistance was seen for nalidixic acid (90.4% and100%) among both S. typhi and S. paratyphi A isolates followed by ciprofloxacin (62.2% and 54.6%) respectively. MDR to first line drugs was observed in a small proportion of S. typhi (1.7%) only. Conclusion The frequency of isolation of S. typhi and S. paratyphi A are in equal proportion and enteric fever is more prevalent in younger age group. It is ideal to adopt bivalent vaccination in Universal immunization schedule. The isolates show sensitivity to first line drugs, paving the way for salvage of the earlier drugs. Cephalosporins still remain the treatment of choice in MDR salmonella isolates. PMID:27437211

  14. Antibiotic resistance profiles and virulence markers of Pseudomonas aeruginosa strains isolated from composts.

    PubMed

    Kaszab, Edit; Szoboszlay, Sándor; Dobolyi, Csaba; Háhn, Judit; Pék, Nikoletta; Kriszt, Balázs

    2011-01-01

    The aim of our work was to determine the presence of Pseudomonas aeruginosa in compost raw materials, immature and mature compost, and compost-treated soil. Twenty-five strains of P. aeruginosa were isolated from a raw material (plant straw), immature and mature compost and compost-treated soil samples. The strains were identified using the PCR method for the detection of species specific variable regions of 16S rDNA. Strains were examined for the presence of five different virulence-related gene sequences (exoA, exoU, exoT, exoS and exoY) and their antibiotic resistance profiles were determined. Based on our results, species P. aeruginosa can reach significant numbers (up to 10(6) MPN/g sample) during composting and 92.0% of the isolated strains carrying at least two gene sequences encoding toxic proteins. Various types of drug resistance were detected among compost originating strains, mainly against third generation Cephalosporins and Carbapenems. Six isolates were able to resist two different classes of antibiotics (third generation Cephalosporins and Carbapenems, wide spectrum Penicillins or Aminoglycosides, respectively). Based on our results, composts can be a source of P. aeruginosa and might be a concern to individuals susceptible to this opportunistic pathogen. PMID:20817443

  15. The use of cephalosporins for gonorrhea: the impending problem of resistance.

    PubMed

    Barry, Pennan M; Klausner, Jeffrey D

    2009-03-01

    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 now left third-generation cephalosporins as the lone class of antimicrobials 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

  16. Review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate.

    PubMed

    Sader, Helio S; Jacobs, Michael R; Fritsche, Thomas R

    2007-03-01

    The antimicrobial spectrum and in vitro potency of the most frequently prescribed orally administered cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil, cephalexin) and amoxicillin/clavulanate are reviewed. These beta-lactam agents have been widely used in the outpatient arena for the treatment of community-acquired respiratory tract and other mild-to-moderate infections. The data presented here were obtained from critical review articles on each of these compounds. Cephalexin and cefaclor were among the least potent and had the narrowest antimicrobial spectrums against the pathogens evaluated. In contrast, cefdinir, cefpodoxime, cefprozil, and cefuroxime were highly active against penicillin-susceptible Streptococcus pneumoniae and retained some activity against penicillin-intermediate strains, whereas amoxicillin/clavulanate was the most active against S. pneumoniae, including most penicillin nonsusceptible strains. Amoxicillin/clavulanate and cefdinir were the most potent compounds against methicillin (oxacillin)-susceptible Staphylococcus aureus, whereas cefpodoxime was the most potent compound against Haemophilus influenzae. Amoxicillin/clavulanate, cefdinir, and cefpodoxime were also active against Moraxella catarrhalis, including beta-lactamase-producing strains. In summary, orally administered "3rd-generation" or extended spectrum cephalosporins exhibited more balanced spectrums of activity against the principal bacterial pathogens responsible for outpatient respiratory tract and other infections when compared with other widely used oral cephalosporins of earlier generations or amoxicillin alone. PMID:17292577

  17. 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

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

    PubMed Central

    2013-01-01

    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

  19. Cephalosporin and carbacephem nephrotoxicity. Roles of tubular cell uptake and acylating potential.

    PubMed

    Tune, B M; Hsu, C Y; Fravert, D

    1996-02-23

    Three beta-lactams, desacetylcephaloglycin, ampicillin, and loracarbef, were studied to test a hypothesis derived from retrospective analysis of previously studied cephalosporins: that beta-lactam nephrotoxicity develops in approximate proportion to tubular cell antibiotic concentrations and lactam ring reactivities. Concentrations of each beta-lactam (and insulin) in rabbit renal cortex and serum were measured at the end of 0.5-hr infusions of 100 mg antibiotic/kg body weight and 0.5 to 0.67 hr later. Total cortical AUCs (total areas under the curve of concentration and time in renal cortex) and transported cortical AUCs (total minus insulin-space beta lactam) were calculated from these measurements. Reactivities, determined by the rate constants of lactam-ring opening at pH 10, were taken from the literature. Nephrotoxicity was quantified by grades of proximal tubular cell necrosis and by serum creatinine concentrations 2 days after infusion of 100-1500 mg/kg of the antibiotics. Desacetylcephaloglycin was slightly less nephrotoxic than cephaloglycin; the AUCs reactivities, and toxicities of these two cephalosporins fit the proposed model, particularly when allowance is made for hepatic and renal deacetylation of cephaloglycin. The very low AUCs, limited reactivity, and absence of nephrotoxicity of ampicillin also fit the model. Loracarbef had a transported AUC less than three times, and reactivity one-thirtieth, those of cefaclor, respectively. Although only at 1500 mg/kg, loracarbef was significantly more nephrotic than cefaclor. If the relativity of loracarbef with its targeted bacterial proteins, which is essentially the same as that of cefaclor, is considered instead of the base hydrolysis rate constant, than loracarbef also fits the model. By the same analysis, the comparatively high in vitro stability of other carbacephems, although pharmaceutically convenient, may not limit their nephrotoxicity. PMID:8619902

  20. 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

  1. Changing patterns and widening of antibiotic resistance in Shigella spp. over a decade (2000-2011), Andaman Islands, India.

    PubMed

    Bhattacharya, D; Bhattacharya, H; Sayi, D S; Bharadwaj, A P; Singhania, M; Sugunan, A P; Roy, S

    2015-02-01

    This study is a part of the surveillance study on childhood diarrhoea in the Andaman and Nicobar Islands; here we report the drug resistance pattern of recent isolates of Shigella spp. (2006-2011) obtained as part of that study and compare it with that of Shigella isolates obtained earlier during 2000-2005. During 2006-2011, stool samples from paediatric diarrhoea patients were collected and processed for isolation and identification of Shigella spp. Susceptibility to 22 antimicrobial drugs was tested and minimum inhibitory concentrations were determined for third-generation cephalosporins, quinolones, amoxicillin-clavulanic acid combinations and gentamicin. A wide spectrum of antibiotic resistance was observed in the Shigella strains obtained during 2006-2011. The proportions of resistant strains showed an increase from 2000-2005 to 2006-2011 in 20/22 antibiotics tested. The number of drug resistance patterns increased from 13 in 2000-2005 to 43 in 2006-2011. Resistance to newer generation fluoroquinolones, third-generation cephalosporins and augmentin, which was not observed during 2000-2005, appeared during 2006-2011. The frequency of resistance in Shigella isolates has increased substantially between 2000-2006 and 2006-2011, with a wide spectrum of resistance. At present, the option for antimicrobial therapy in shigellosis in Andaman is limited to a small number of drugs. PMID:24763083

  2. Targeting metallo-carbapenemases via modulation of electronic properties of cephalosporins.

    PubMed

    Yang, Hao; Young, Heather; Yu, Sophia; Sutton, Larry; Crowder, Michael W

    2014-12-01

    The global proliferation of metallo-carbapenemase-producing Enterobacteriaceae has created an unmet need for inhibitors of these enzymes. The rational design of metallo-carbapenemase inhibitors requires detailed knowledge of their catalytic mechanisms. Nine cephalosporins, structurally identical except for the systematic substitution of electron-donating and withdrawing groups in the para position of the styrylbenzene ring, were synthesized and utilized to probe the catalytic mechanism of New Delhi metallo-β-lactamase (NDM-1). Under steady-state conditions, K(m) values were all in the micromolar range (1.5-8.1 μM), whereas k(cat) values varied widely (17-220 s(-1)). There were large solvent deuterium isotope effects for all substrates under saturating conditions, suggesting a proton transfer is involved in the rate-limiting step. Pre-steady-state UV-visible scans demonstrated the formation of short-lived intermediates for all compounds. Hammett plots yielded reaction constants (ρ) of -0.34 ± 0.02 and -1.15 ± 0.08 for intermediate formation and breakdown, respectively. Temperature-dependence experiments yielded ΔG(‡) values that were consistent with the Hammett results. These results establish the commonality of the formation of an azanide intermediate in the NDM-1-catalysed hydrolysis of a range cephalosporins with differing electronic properties. This intermediate is a promising target for judiciously designed β-lactam antibiotics that are poor NDM-1 substrates and inhibitors with enhanced active-site residence times. PMID:25220027

  3. Comparative Serum Levels and Protective Activity of Parenterally Administered Cephalosporins in Experimental Animals

    PubMed Central

    Fare, Louis R.; Actor, Paul; Sachs, Carl; Phillips, Lillian; Joloza, MacDonald; Pauls, John F.; Weisbach, Jerry A.

    1974-01-01

    Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs. PMID:15828185

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

    PubMed Central

    Pathak, Ashish; Stålsby 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 (2008–2011) using a customized form. Data from inpatients aged 0–18 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

  5. Crystal structure of EstSRT1, a family VIII carboxylesterase displaying hydrolytic activity toward oxyimino cephalosporins.

    PubMed

    Cha, Sun-Shin; An, Young Jun

    2016-09-16

    EstSRT1 is a family VIII carboxylesterase that hydrolyzes oxyimino third- and fourth-generation cephalosporins, first-generation cephalosporins and ester substrates. According to the crystal structure of EstSRT1 (2.0-Å resolution), this protein contains a large α/β domain and a small α-helical domain and harbors three catalytic residues (Ser71, Lys74, and Tyr160) in the cavity at the domain interface, similarly to other family VIII carboxylesterases. Comparison of the structures of EstSRT1 and EstU1, a family VIII carboxylesterase with no hydrolytic activity toward bulky oxyimino cephalosporins, revealed that EstSRT1 has a smaller active site, despite its extended substrate range. The B-factors of the active site segments that could potentially contact with the oxyimino groups and the R2 side chains of oxyimino cephalosporins are higher in EstSRT1 than in EstU1, thus suggesting the role of the active site's structural flexibility in the extension of EstSRT1's substrate spectrum. PMID:27501751

  6. 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 ...

  7. Value of integron detection for predicting antibiotic resistance in patients with Gram-negative septicaemia.

    PubMed

    Barraud, Olivier; François, Bruno; Chainier, Delphine; Vignaud, Julie; Ploy, Marie-Cécile

    2014-10-01

    Multidrug-resistant Enterobacteriaceae are a major public health threat and complicate the choice of drugs for empirical antibiotic therapy, especially in sepsis patients who require rapid, appropriate treatment. The objective of this study was to examine the value of integrons as a global predictive marker of acquired antibiotic resistance in septicaemia-causing Enterobacteriaceae by direct detection in positive blood cultures. The integron genetic marker can be detected in a single test, whereas multiple PCRs are needed to detect the hundreds of known antibiotic resistance genes. A total of 166 positive blood cultures were included in the study, and integrons were detected with a quantitative PCR method both in positive blood cultures and isolated Enterobacteriaceae. The results of integron detection directly on positive blood cultures were consistent in 98.8% of cases with integron detection in isolated Enterobacteriaceae. Negative predictive values (NPVs) were >90% for resistance to third-generation cephalosporins, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole. In the current context of antibiotic stewardship, these good NPVs indicate that this method might be useful for preserving broad-spectrum antibiotics. The results of this proof-of-concept study must be confirmed in order to demonstrate the clinical relevance of integron detection, not only in positive blood cultures but also, to gain time, in raw biological samples. PMID:25130099

  8. Antibiotic susceptibility of respiratory pathogens recently isolated in Italy: focus on cefditoren.

    PubMed

    Tempera, G; Furneri, P M; Carlone, N A; Cocuzza, C; Rigoli, R; Musumeci, R; Pilloni, A P; Prenna, M; Tufano, M A; Tullio, V; Vitali, L A; Nicoletti, G

    2010-06-01

    The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in Italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community-acquired respiratory tract infections (CARTI). Ceftditoren, out of all the beta-lactams studied, had the lowest MIC(90 )against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae , independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC(90)s were found for the macrolides (4 - 16 mg/l) and cefaclor (4 - 32 mg/l). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated MIC(90 )values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC(50)/MIC(90 )values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC(90)s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC(90)s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some

  9. [Cephalosporin-Acid Synthetase of Escherichia coli Strain VKPM B-10182: Genomic Context, Gene Identification, Producer Strain Production].

    PubMed

    Eldarov M, A; Sklyarenko, A V; Mardanov, A V; Beletsky, A V; Zhgun, A A; Dumina, M V; Medvedeva, N V; Satarova, D E; Ravin, N V; Yarockii, S V

    2015-01-01

    An enzyme of cephalosporin-acid synthetase produced by the E. coli strain VKPM B-10182 has specificity for the synthesis of β-lactam antibiotics of the cephalosporin acids class (cefazolin, cefalotin, cefezole etc.). A comparison of the previously determined genomic sequence of E. coli VKPM B-10182 with a genome of the parent E. coli strain ATCC 9637 was performed. Multiple mutations indicating the long selection history of the strain were detected, including mutations in the genes of RNase and β-lactamases that could enhance the level of enzyme synthesis and reduce the degree of degradation of the synthesized cephalosporin acids. The CASA gene--a direct homolog of the penicillin G-acylase gene--was identified by bioinformatics methods. The homology of the gene was confirmed by gene cloning and the expression and determination of its enzymatic activity in the reaction of cefazolin synthesis. The CASA gene was isolated and cloned into the original expression vector, resulting in an effective E. coli BL2l(DE3) pMD0107 strain producing CASA. PMID:26596082

  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 Stålsby

    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

  11. Surveillance and Control of Antibiotic Resistance in the Mediterranean Region

    PubMed Central

    Ricciardi, Walter; Giubbini, Gabriele; Laurenti, Patrizia

    2016-01-01

    Antibiotic resistance is one of the most relevant problems in the healthcare: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising length to stay (LOS), morbidity and mortality in those patients. The importance of the antibiotic resistance and its spread around the world, gave rise to the activation of several surveillance systems, based especially on the collection of laboratory data to local or national level. The objective of this work is to carry out a review of the scientific literature existing on the topic and scientific activities related to surveillance of antibiotic resistance in the countries bordering the Mediterranean Sea. Recent Data from European Centre for Disease Prevention and Control (November 2015) show, for different combinations bacterium-drug, an increase of resistance from North to South and from West to East of Europe. It is of particular concern the phenomenon of resistance carried out by some gram-negative, specifically Klebsiella pneumoniae and Escherichia coli to third-generation cephalosporin, often combined in opposition to fluoroquinolones and aminoglycosides. Is particularly high the incidence of resistance to carbapenems by strains of Enterobacteriaceae (Klebsiella included). The resistance exerted by MRSA (Methicillin-resistant Staphylococcus aureus) continues to be relevant, albeit showing some decline in recent years. The incidence of resistance carried on by Streptococcus pneumoniae is stable and is mainly relevant to macrolides. Finally, a significant increase in recording relatively exercised by Enterococcus faecium to Vancomycin. Detecting, preventing, and controlling antibiotic resistance requires strategic, coordinated, and sustained efforts. It also depends on the engagement of governments, academia, industry, healthcare providers, the general public, and the agricultural community, as well as international partners. Committing to combating antibiotic-resistant microbes does support

  12. Surveillance and Control of Antibiotic Resistance in the Mediterranean Region.

    PubMed

    Ricciardi, Walter; Giubbini, Gabriele; Laurenti, Patrizia

    2016-01-01

    Antibiotic resistance is one of the most relevant problems in the healthcare: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising length to stay (LOS), morbidity and mortality in those patients. The importance of the antibiotic resistance and its spread around the world, gave rise to the activation of several surveillance systems, based especially on the collection of laboratory data to local or national level. The objective of this work is to carry out a review of the scientific literature existing on the topic and scientific activities related to surveillance of antibiotic resistance in the countries bordering the Mediterranean Sea. Recent Data from European Centre for Disease Prevention and Control (November 2015) show, for different combinations bacterium-drug, an increase of resistance from North to South and from West to East of Europe. It is of particular concern the phenomenon of resistance carried out by some gram-negative, specifically Klebsiella pneumoniae and Escherichia coli to third-generation cephalosporin, often combined in opposition to fluoroquinolones and aminoglycosides. Is particularly high the incidence of resistance to carbapenems by strains of Enterobacteriaceae (Klebsiella included). The resistance exerted by MRSA (Methicillin-resistant Staphylococcus aureus) continues to be relevant, albeit showing some decline in recent years. The incidence of resistance carried on by Streptococcus pneumoniae is stable and is mainly relevant to macrolides. Finally, a significant increase in recording relatively exercised by Enterococcus faecium to Vancomycin. Detecting, preventing, and controlling antibiotic resistance requires strategic, coordinated, and sustained efforts. It also depends on the engagement of governments, academia, industry, healthcare providers, the general public, and the agricultural community, as well as international partners. Committing to combating antibiotic-resistant microbes does support

  13. 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

  14. 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.

  15. In vitro efficacy of six cephalosporins tested against Enterobacteriaceae isolated at 38 North American medical centres participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

    PubMed

    Jones, R N; Jenkins, S G; Hoban, D J; Pfaller, M A; Ramphal, R

    2000-07-01

    The SENTRY Antimicrobial Surveillance Program is an ongoing international collaboration that monitors the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial infections. SENTRY data on the current cephalosporin susceptibility patterns (1997-98) of North American isolates of clinically important Enterobacteriaceae were analyzed. Susceptibility to a selection of cephalosporins was assessed at a central laboratory using reference broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. The third- and fourth-generation cephalosporins tested demonstrated excellent activity against Escherichia coli and Klebsiella pneumoniae, whereas some of the older agents maintained good efficacy. Extended spectrum beta-lactamases were detected in all regions of the United States and Canada (1.8-10.7%). Cefepime was the most active agent tested against pathogens with the potential for enzyme-mediated resistance due to Amp C. The third-generation agents maintained acceptable efficacy against Serratia marcescens, but were less effective against Citrobacter and Enterobacter species. The older cephalosporins were generally inadequate against these pathogens, in contrast to cefepime, which was the widest spectrum cephalosporin overall. Some significant regional variations in spectrum were detected. PMID:10854806

  16. Carriage of antibiotic-resistant bacteria by healthy children.

    PubMed

    Millar, M R; Walsh, T R; Linton, C J; Zhang, S; Leeming, J P; Bennett, P M

    2001-05-01

    The frequency of carriage of antibiotic-resistant bacteria in healthy 7- and 8-year-old children in Bristol was studied. Children born in Avon between 1 April 1991 and 31 December 1992, attending the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) 7 year follow-up clinic, formed the study population. Carriage was estimated using mouth and stool samples. None of 105 children on whom information was available had received tetracycline, chloramphenicol, ciprofloxacin or an extended-spectrum cephalosporin in the previous year. Staphylococcus aureus was isolated from mouthwashes from 200 (37.1%) of 539 children sampled. Six (3%) of the isolates were resistant to chloramphenicol or tetracycline and four (2%) were methicillin resistant. Haemophilus spp. were isolated from 369 (72%) of 513 samples and 63 (17%) were ampicillin resistant, 49 (13.3%) were erythromycin resistant and seven (1.9%) were tetracycline resistant. Branhamella catarrhalis was isolated from 333 (74%) of 450 samples. Twenty-eight (8.4%) were erythromycin resistant and 14 (4.2%) strains were tetracycline resistant. Group A beta-haemolytic streptococci were isolated from 17 of 507 children sampled. One (5.9%) was tetracycline resistant. Stool samples were returned from 335 (62%) of 539 children from whom they were requested. Eleven per cent of samples yielded Gram-negative bacilli with high-level resistance to chloramphenicol, which was frequently linked to resistance to ampicillin, spectinomycin and streptomycin. Isolates demonstrating resistance to the third-generation cephalosporin ceftazidime were recovered from 17 subjects (3.2%). Six (35%) of 17 isolates possessed extended-spectrum beta-lactamases. Healthy children carry bacteria resistant to antibiotics to which children are not usually exposed. Resistance to ceftazidime, chloramphenicol and tetracycline may be co-selected by exposure to other antibiotics used in children or may be acquired from family members, pets, other children or

  17. 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 ...

  18. Empiric Antibiotic Therapy of Nosocomial Bacterial Infections.

    PubMed

    Reddy, Pramod

    2016-01-01

    Broad-spectrum antibiotics are commonly used by physicians to treat various infections. The source of infection and causative organisms are not always apparent during the initial evaluation of the patient, and antibiotics are often given empirically to patients with suspected sepsis. Fear of attempting cephalosporins and carbapenems in penicillin-allergic septic patients may result in significant decrease in the spectrum of antimicrobial coverage. Empiric antibiotic therapy should sufficiently cover all the suspected pathogens, guided by the bacteriologic susceptibilities of the medical center. It is important to understand the major pharmacokinetic properties of antibacterial agents for proper use and to minimize the development of resistance. In several septic patients, negative cultures do not exclude active infection and positive cultures may not represent the actual infection. This article will review the important differences in the spectrum of commonly used antibiotics for nosocomial bacterial infections with a particular emphasis on culture-negative sepsis and colonization. PMID:24413366

  19. In vitro and in vivo antibacterial activities of BO-1341, a new antipseudomonal cephalosporin.

    PubMed Central

    Nakagawa, S; Sanada, M; Matsuda, K; Hashizume, T; Asahi, Y; Ushijima, R; Ohtake, N; Tanaka, N

    1989-01-01

    BO-1341, a new antipseudomonal semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefotaxime, and cefoperazone. The in vitro activity of BO-1341 was generally superior or comparable to the activities of the reference antibiotics against clinical isolates of the family Enterobacteriaceae. BO-1341 was highly active against Pseudomonas aeruginosa (MIC for 90% of the strains tested, 1.56 micrograms/ml), Pseudomonas maltophilia (MIC for 50% of the strains tested, 1.56 micrograms/ml), and Acinetobacter calcoaceticus (MIC for 90% of the strains tested, 3.13 micrograms/ml). Furthermore, BO-1341 was highly active against P. aeruginosa isolates resistant to the other antibiotics. Of 199 P. aeruginosa isolates tested, only 2 were resistant to BO-1341. These two strains were also resistant to ceftazidime, cefotaxime, and cefoperazone. Haemophilus influenzae, Branhamella catarrhalis, and nonenteric streptococci were also susceptible to BO-1341, but Staphylococcus aureus, Streptococcus faecalis, and Bacteroides fragilis were not susceptible to the compound. The protective efficacy against experimental infections in mice caused by nine strains of gram-negative bacteria, including P. aeruginosa, reflected the potent in vitro activity. PMID:2510590

  20. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions, 2010.

    PubMed

    Lahra, Monica M

    2012-03-01

    The World Health Organization (WHO) Gonococcal Antimicrobial Surveillance Programme (GASP) has conducted continuous surveillance of antimicrobial resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region (WPR) to optimise antibiotic treatment and control of gonococcal disease since 1992. From 2007, this has been enhanced by the inclusion of data from the WHO South East Asian Region (SEAR). Over time, there has been recruitment of additional centres in both regions. This report provides an analysis of antimicrobial resistance in N. gonorrhoeae in the WHO WPR and SEAR derived from results of the 2010 GASP surveillance. In 2010 there were 9,744 N. gonorrhoeae isolates examined for their susceptibility to one or more of the antibiotics used for the treatment of gonorrhoea, incorporating External Quality Assurance controlled methods, from reporting centres in 19 countries and/or jurisdictions. A high proportion of penicillin and quinolone resistance was again detected amongst isolates tested in the 'Asian' countries of WHO WPR and SEAR. In contrast, lower levels of penicillin and quinolone resistance were reported from the Pacific Islands of Fiji and New Caledonia. The proportion of gonococci reported as having 'decreased susceptibility' to the third-generation cephalosporin antibiotic ceftriaxone varied widely, ranging from 1.3% to 55.8%. There is a continued need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels, and to relate these to treatment outcome. Azithromycin resistance was very low in most countries reporting, except in Mongolia where it was 34%. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit high-level plasmid mediated resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and

  1. 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

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

    PubMed

    Bassetti, Matteo; Merelli, Maria; Temperoni, Chiara; Astilean, Augusta

    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

  3. 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

  4. 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.

  5. Severe sepsis and septic shock in pre-hospital emergency medicine: survey results of medical directors of emergency medical services concerning antibiotics, blood cultures and algorithms.

    PubMed

    Casu, Sebastian; Häske, David

    2016-06-01

    Delayed antibiotic treatment for patients in severe sepsis and septic shock decreases the probability of survival. In this survey, medical directors of different emergency medical services (EMS) in Germany were asked if they are prepared for pre-hospital sepsis therapy with antibiotics or special algorithms to evaluate the individual preparations of the different rescue areas for the treatment of patients with this infectious disease. The objective of the survey was to obtain a general picture of the current status of the EMS with respect to rapid antibiotic treatment for sepsis. A total of 166 medical directors were invited to complete a short survey on behalf of the different rescue service districts in Germany via an electronic cover letter. Of the rescue districts, 25.6 % (n = 20) stated that they keep antibiotics on EMS vehicles. In addition, 2.6 % carry blood cultures on the vehicles. The most common antibiotic is ceftriaxone (third generation cephalosporin). In total, 8 (10.3 %) rescue districts use an algorithm for patients with sepsis, severe sepsis or septic shock. Although the German EMS is an emergency physician-based rescue system, special opportunities in the form of antibiotics on emergency physician vehicles are missing. Simultaneously, only 10.3 % of the rescue districts use a special algorithm for sepsis therapy. Sepsis, severe sepsis and septic shock do not appear to be prioritized as highly as these deadly diseases should be in the pre-hospital setting. PMID:26719078

  6. Antibiotic Resistance

    MedlinePlus

    Antibiotics are medicines that fight bacterial infections. Used properly, they can save lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able to resist the effects of an antibiotic. Using antibiotics can lead to resistance. ...

  7. Improving the quality of antibiotic prescribing in the NHS by developing a new Antimicrobial Stewardship Programme: Start Smart--Then Focus.

    PubMed

    Ashiru-Oredope, Diane; Sharland, Mike; Charani, Esmita; McNulty, Cliodna; Cooke, Jonathan

    2012-07-01

    There has been dramatic change in antibiotic use in English hospitals. Data from 2004 and 2009 show that the focus on reducing fluoroquinolone and second- and third-generation cephalosporin use seems to have been heeded in NHS secondary care, and has been associated with a substantial decline in hospital Clostridium difficile rates. However, there has been a substantial increase in use of co-amoxiclav, carbapenems and piperacillin/tazobactam. In primary care, antibiotic prescribing fell markedly from 1995 to 2000, but has since risen steadily to levels seen in the early 1990s. There remains a 2-fold variation in antimicrobial prescribing among English General Practices. In 2010, the NHS Atlas of Variation documented a 3-fold variation in the prescription of quinolones and an 18-fold variation in cephalosporins by Primary Care Trusts across England. There is a clear need to improve antimicrobial prescribing. This paper describes the development of new antimicrobial stewardship programmes for primary care and hospitals by the Department of Health's Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection: Antimicrobial Stewardship in Primary Care Initiative. The secondary care programme promotes the rapid prescription of the right antibiotic at the right dose at the right time, followed by active review for all patients still on antibiotics 48 h after admission. The five options available are to stop, switch to oral, continue and review again, change (if possible to a narrower spectrum) or move to outpatient parenteral antibiotic therapy. A range of audit and outcome tools has been developed, but to maintain optimal antimicrobial usage, monitoring of local and national quantitative and qualitative data on prescribing and consumption is required, linked to the development of key performance indicators in primary, secondary and tertiary care. PMID:22855879

  8. Preparation of 3-deacetyl cephalosporins by Aspergillus niger lipase.

    PubMed

    Carrea, G; Corcelli, A; Palmisano, G; Riva, S

    1996-12-20

    Lipase from Aspergillus niger was used for the selective hydrolysis of the 3-O-acetate of cephalosporin C to give an intermediate useful for further chemical elaborations. This lipase was purified to homogeneity and its properties compared with previously published data that present some discrepancies. The lipase proved to be very effective in catalyzing 3-O-acetate hydrolysis and versatile toward substitution on the beta-lactamic ring. In fact, as an example, two other cephalosporinic derivatives, cephalotin and cefotaxime, were efficiently deacetylated. The lipase was immobilized on Eupergit C and employed continuously in either a column or a batch reactor for 2 months without appreciable loss of activity. (c) 1996 John Wiley & Sons, Inc. PMID:18629943

  9. Efflux Pump Blockers in Gram-Negative Bacteria: The New Generation of Hydantoin Based-Modulators to Improve Antibiotic Activity

    PubMed Central

    Otręebska-Machaj, Ewa; Chevalier, Jacqueline; Handzlik, Jadwiga; Szymańska, Ewa; Schabikowski, Jakub; Boyer, Gérard; Bolla, Jean-Michel; Kieć-Kononowicz, Katarzyna; Pagès, Jean-Marie; Alibert, Sandrine

    2016-01-01

    Multidrug resistant (MDR) bacteria are an increasing health problem with the shortage of new active antibiotic agents. Among effective mechanisms that contribute to the spread of MDR Gram-negative bacteria are drug efflux pumps that expel clinically important antibiotic classes out of the cell. Drug pumps are attractive targets to restore the susceptibility toward the expelled antibiotics by impairing their efflux activity. Arylhydantoin derivatives were investigated for their potentiation of activities of selected antibiotics described as efflux substrates in Enterobacter aerogenes expressing or not AcrAB pump. Several compounds increased the bacterial susceptibility toward nalidixic acid, chloramphenicol and sparfloxacin and were further pharmacomodulated to obtain a better activity against the AcrAB producing bacteria. PMID:27199950

  10. Antibiotic sensitivity and resistance in children with urinary tract infection in Sanliurfa

    PubMed Central

    Abuhandan, Mahmut; Güzel, Bülent; Oymak, Yeşim; Çiftçi, Halil

    2013-01-01

    Objective: This study aimed to evaluate antibiotic resistance in the province of Şanliurfa and to observe any difference between antibiotic resistance rates. Material and methods: The study comprised 107 children who presented at the pediatric polyclinic with complaints of urinary tract infection with the diagnosis of urinary tract infection and whose urine cultures exhibited bacterial growth. The patients were analyzed with respect to the frequency of proliferating pathogens, sensitivity to the antibiotics used and the rates of developed resistance to the antibiotics. Results: A total of 107 patients aged between 1 year and 15 years were included in the study, encompassing 14 (13.1%) males and 93 (86.9%) females. According to the urine culture results, proliferation of Escherichia coli (E. coli) was observed in 69 (64.5%), Klebsiella spp. in 13 (12.1%), Proteus mirabilis in 9 (8.4%), Staphylococcus aureus in 5 (4.7%), Pseudomonas aeruginosa in 5 (4.7%), Acinetobacter spp. in 3 (2.8%) and Enterococcus spp. in 3 (2.8%) patients. For proliferating E. coli, high resistance rates to ceftriaxone (39.5%), nitrofurantoin (19.7%), ampicillin-sulbactam (64.1%), co-trimoxazole (41.5%), amoxicillinclavulanate (51.7%) and cefuroxime (38.1%) were observed. All of isolated microorganisms were resistant to ampicillin-sulbactam, amoxicillin-clavulanate, co-trimoxazole, ceftriaxone, cefuroxime and cefoxitin in decreasing frequencies. The most effective antimicrobial agents were determined to be imipenem, sulpera-zone, quinolone and aminoglycosides. Conclusion: In our region, parenteral antibiotics that should be selected for the empirical treatment of UTIs in all age groups are the aminoglycosides and 3rd generation cephalosporines. In contrast to other studies, these results suggest that co-trimoxazole should be used for children aged 0–1, and 2nd generation cephalosporins should be used for the oral treatment of children aged 1–5 due to the low rate of resistance to

  11. 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; Månsson, 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

  12. Antibiotic Agents

    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 ...

  13. Antibiotic Safety

    MedlinePlus

    ... specific to women Antibiotics can lead to vaginal yeast infections. This happens because antibiotics kill the normal bacteria in the vagina and this causes yeast to grow rapidly. Symptoms of a yeast infection ...

  14. The LisRK Signal Transduction System Determines the Sensitivity of Listeria monocytogenes to Nisin and Cephalosporins

    PubMed Central

    Cotter, Paul D.; Guinane, Caitriona M.; Hill, Colin

    2002-01-01

    The Listeria monocytogenes two-component signal transduction system, LisRK, initially identified in strain LO28, plays a significant role in the virulence potential of this important food-borne pathogen. Here, it is shown that, in addition to its major contribution in responding to ethanol, pH, and hydrogen peroxide stresses, LisRK is involved in the ability of the cell to tolerate important antimicrobials used in food and in medicine, e.g., the lantibiotic nisin and the cephalosporin family of antibiotics. A ΔlisK mutant (lacking the LisK histidine kinase sensor component) displays significantly enhanced resistance to the lantibiotic nisin, a greatly enhanced sensitivity to the cephalosporins, and a large reduction in the expression of three genes thought to encode a penicillin-binding protein, another histidine kinase (other than LisK), and a protein of unknown function. Confirmation of the role of LisRK was obtained when the response regulator, LisR, was overexpressed using both constitutive and inducible (nisin-controlled expression) systems. Under these conditions we observed a reversion of the ΔlisK mutant to wild-type growth kinetics in the presence of nisin. It was also found that overexpression of LisR complemented the reduced expression of two of the aforementioned genes. These results demonstrate the important role of LisRK in the response of L. monocytogenes to a number of antimicrobial agents. PMID:12183229

  15. Tolerance of staphylococci to bactericidal antibiotics.

    PubMed

    Vaudaux, Pierre; Lew, Daniel P

    2006-05-01

    Antibiotic therapy for deep-seated staphylococcal infections, especially when they are associated with artificial devices used for orthopedic surgery is often associated with failure. Standard anti-staphylococcal bactericidal antibiotics, such as semi-synthetic penicillins, cephalosporins, or glycopeptides, are effective when given prophylactically in clinical conditions or experimental trials of implant-related infections. However, the efficacy of all anti-staphylococcal agents is seriously diminished on already established implant-related deep-seated infections, which then frequently require surgical implant removal to obtain a cure. The failure of antibiotic therapy to cure established staphylococcal foreign-body infections may arise in part from a broad-spectrum phenotypic tolerance expressed in vivo to different classes of antimicrobial agents. The molecular and physiological mechanisms of this in vivo tolerance remain poorly understood. PMID:16651066

  16. Analysis of plasmid-mediated quinolone and oxyimino-cephalosporin resistance mechanisms in Uruguayan Salmonella enterica isolates from 2011-2013.

    PubMed

    Cordeiro, Nicolás F; Nabón, Adriana; García-Fulgueiras, Virginia; Álvez, Marcelo; Sirok, Alfredo; Camou, Teresa; Vignoli, Rafael

    2016-09-01

    This study characterised the mechanisms of fluoroquinolone and oxyimino-cephalosporin resistance in human Salmonella enterica isolates in Uruguay. Salmonella enterica isolates were collected from 2011-2013 and were selected based on non-susceptibility to ciprofloxacin and/or oxyimino-cephalosporins. The disk diffusion assay was performed for various antibiotics, and the ciprofloxacin minimum inhibitory concentration (MIC) was determined following CLSI guidelines. Genetic relatedness was determined following PulseNet protocols. Extended-spectrum β-lactamases, ampC alleles and plasmid-mediated quinolone resistance were characterised by PCR and sequencing. Plasmid analyses were carried out by conjugation or transformation assays, and plasmid-encoded genes were identified by PCR. Mutations in the quinolone resistance-determining region of gyrases were sought by PCR and sequencing. Among 579 isolates, 105 (18.4%) ciprofloxacin-non-susceptible (CIP-NS) isolates, 9 (1.6%) oxyimino-cephalosporin-resistant isolates and 2 (0.3%) isolates resistant to both antibiotic families were detected. Thirteen isolates carried qnrB alleles (twelve qnrB19 and one qnrB2), four carried blaCTX-M-8, two blaCTX-M-14, two blaSHV-2 and three blaCMY-2-like genes. No correlation was found between mutations in gyrases and ciprofloxacin MICs. Several co-circulating clones of S. enterica ssp. enterica serovar Typhimurium were detected; conversely, S. enterica ssp. enterica serovar Enteritidis corresponded mainly to a single circulating clone. Nine (75%) of twelve of CIP-NS extraintestinal isolates shared the same pulsotype with intestinal isolates. During the study period, the frequency of CIP-NS isolates increased, albeit with ciprofloxacin MICs of 0.125-0.5mg/L. Detection of the same quinolone-resistant clones recovered both from intestinal and extraintestinal samples highlights the significance of epidemiological surveillance of antibiotic susceptibility for every human Salmonella isolate. PMID

  17. Antibiotic Treatment and Surgery for Acute Hematogenous Calcaneal Osteomyelitis of Childhood.

    PubMed

    Pääkkönen, Markus; Kallio, Markku J T; Peltola, Heikki; Kallio, Pentti E

    2015-01-01

    Acute hematogenous calcaneal osteomyelitis characteristically affects children. A recent trend has emerged toward shorter courses of antibiotics. In our randomized, prospective treatment trial of children aged 3 months to 15 years, the intravenous antibiotic (clindamycin or a first-generation cephalosporin) was given only for the first 2 to 4 days and the remainder of the 20- to 30-day course was completed orally. A bone sample for culture was to be taken routinely, but all additional surgery was performed on special demand. We performed a retrospective subanalysis of cases affecting the calcaneus. The follow-up period was 1 year. Of the 14 participants enrolled, 11 completed the 1-year follow-up period, and their data were analyzed. Staphylococcus aureus was the cause of 10 cases; all strains were methicillin sensitive. The median intravenous treatment duration was 3 days. Four patients required open incisional trepanation (trephination). All participants attending the 1-year follow-up examination had fully recovered. The outcome of calcaneal osteomyelitis caused by methicillin-sensitive S. aureus in a child will be good, if the patient seeks treatment early and antibiotic therapy is started promptly. A bone biopsy is needed to obtain a representative sample for bacteriology. PMID:25912854

  18. Epidemic and virulence characteristic of Shigella spp. with extended-spectrum cephalosporin resistance in Xiaoshan District, Hangzhou, China

    PubMed Central

    2014-01-01

    Background Shigellae have become increasingly resistant to the extended-spectrum cephalosporin (ESC) worldwide and pose a great challenge to anti-infection treatment options. The purpose of this study was to determine the resistance, cephalosporin resistance mechanisms, virulence characteristic and genotype of ESC-resistant Shigella. Methods From 2008 to 2012, Shigella isolates collected from diarrhea patients were detected for antibiotics sensitivity by disk diffusion, cephalosporin resistance determinants and virulence genes using polymerase chain reaction (PCR) and genotyping through enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR). Results A total of 356 Shigella isolates were gathered, and 198 (55.6%, 58 S. flexneri and 140 S. sonnei) were resistant to ESC. All ESC-resistant isolates were susceptible to imipenem, and only 0.5% isolate was resistant to piperacillin/tazobactam. ESC-resistant S. flexneri showed high degrees of resistance to ampicillin (100%), ampicillin/sulbactam (96.6%), piperacillin (100%), trimethoprim/sulfamethoxazole (74.1%), ciprofloxacin (74.1%), levofloxacin (53.4%), ceftazidime (58.6%) and cefepime (58.6%). ESC-resistant S. sonnei exhibited high resistance rates to ampicillin (100%), piperacillin (100%) and trimethoprim/sulfamethoxazole (96.4%). Cephalosporin resistance genes were confirmed in 184 ESC-resistant isolates. blaCTX-M types (91.8%, mainly blaCTX-M-14, blaCTX-M-15 and blaCTX-M-57) were most prevalent, followed by blaOXA-30 (26.3%). Over 99.0% ESC-resistant isolates harbored virulence genes ial, ipaH, virA and sen. However, set1 were more prevalent in ESC-resistant S. flexneri isolates than in S. sonnei isolates. ERIC-PCR results showed that 2 and 3 main genotypes were detected in ESC-resistant S. flexneri and S. sonnei, respectively. Conclusion Our findings indicated that a high prevalence of ESC-resistant Shigella mediated mainly by blaCTX-M with stronger resistance and virulence, and the existence

  19. 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

  20. Assessing the contributions of the LiaS histidine kinase to the innate resistance of Listeria monocytogenes to nisin, cephalosporins, and disinfectants.

    PubMed

    Collins, Barry; Guinane, Caitriona M; Cotter, Paul D; Hill, Colin; Ross, R Paul

    2012-04-01

    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

  1. Cephamycins, a new family of beta-lactam antibiotics. I. Production by actinomycetes, including Streptomyces lactamdurans sp. n.

    PubMed

    Stapley, E O; Jackson, M; Hernandez, S; Zimmerman, S B; Currie, S A; Mochales, S; Mata, J M; Woodruff, H B; Hendlin, D

    1972-09-01

    A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of Streptomyces, including a newly described species, S. lactamdurans. These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins. PMID:4790552

  2. In vitro activities of ureidopenicillins alone and in combination with amikacin and three cephalosporin antibiotics.

    PubMed Central

    Moody, J A; Peterson, L R; Gerding, D N

    1984-01-01

    The MIC and MBC activity of mezlocillin alone and in combination with two concentrations of ceftizoxime, moxalactam, and amikacin and a single concentration of cefoxitin was studied in a broth microdilution partial checkerboard against 472 strains of aerobic gram-negative and gram-positive bacteria. Azlocillin was tested alone and in the same combinations against Pseudomonas aeruginosa. Of the gram-negative bacilli tested, 38% were gentamicin resistant. Antagonism (less than or equal to a fourfold ureidopenicillin MIC increase) was observed frequently with combinations of ureidopenicillins plus cefoxitin and sporadically with ureidopenicillins plus ceftizoxime or moxalactam. Partial synergism (less than or equal to a fourfold ureidopenicillin MIC decrease) was evident with both combinations of ureidopenicillins plus amikacin and ureidopenicillins plus ceftizoxime or moxalactam, the percentage being dependent upon the individual species and combinations. PMID:6435516

  3. Two-Year Surveillance of Antibiotic Resistance in Streptococcus pneumoniae in Four African Cities

    PubMed Central

    Benbachir, Mohamed; Benredjeb, Saida; Boye, Cheick Saadbouh; Dosso, Mireille; Belabbes, Houria; Kamoun, Aouatef; Kaire, Omar; Elmdaghri, Naima

    2001-01-01

    Worldwide spread of antibiotic resistance in Streptococcus pneumoniae is a major problem. However, data from West and North African countries are scarce. To study the level of resistance and compare the situations in different cities, a prospective study was conducted in Abidjan (Ivory Coast), Casablanca (Morocco), Dakar (Senegal), and Tunis (Tunisia), from 1996 to 1997. The resistances to eight antibiotics of 375 isolates were studied by E test, and the results were interpreted using the breakpoints recommended by the National Committee for Clinical Laboratory Standards. Overall, 30.4% of the isolates were nonsusceptible to penicillin G (25.6% were intermediate and 4.8% were resistant). Amoxicillin (96.3% were susceptible) and parenteral third-generation cephalosporins (92.7%) were highly active. Resistance to chloramphenicol was detected in 8.6% of the isolates. High levels of resistance were noted for erythromycin (28%), tetracycline (38.3%), and cotrimoxazole (36.4%). Resistance to rifampin was rare (2.1%). There were significant differences in resistance rates between individual countries. Multiple resistance was more frequent in penicillin-nonsusceptible isolates than in penicillin-susceptible isolates. Recommendations for treatment could be generated from these results in each participating country. PMID:11158769

  4. Induction of beta-lactamase by various beta-lactam antibiotics in Enterobacter cloacae.

    PubMed Central

    Minami, S; Yotsuji, A; Inoue, M; Mitsuhashi, S

    1980-01-01

    The induction of beta-lactamase in Enterobacter cloacae GN5797 was studied by using 23 beta-lactam antiobiotics, including newly introduced drugs, as inducers. the beta-lactam antibiotics can be classified into three groups on the basis of their inducer activity. Among the tested cephalosporins, cephamycin derivatives such as cefoxitin, cefmetazole, and YM09330 had high inducer activity even at low drug concentrations. On the other hand, cefoperazone, cefsulodin, piperacillin, and apalcillin showed low inducer activity when compared with the other cephalosporins. PMID:6968541

  5. Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisiae.

    PubMed

    Fujita, Ken-Ichi; Tani, Kazunori; Usuki, Yoshinosuke; Tanaka, Toshio; Taniguchi, Makoto

    2004-08-01

    UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. C9-UK-2A, which has been prepared to improve the duration of the antifungal activity of UK-2A, shows durable fungicidal activities against various species of fungi and induces both membrane injury and the generation of cellular reactive oxygen species (ROS) against Rhodotorula mucilaginosa IFO 0001 cells. We found that C9-UK-2A inhibited the vegetative growth of Saccharomyces cerevisiae IFO 0203 cells accompanying cellular ROS generation in Sabouraud dextrose (SD) medium, which contained a fermentable carbon source. The ROS generation was completely restricted by pretreatment with a lipophilic antioxidant alpha-tocopherol. In addition, the pretreatment with the antioxidant protected against the growth inhibition induced by C9-UK-2A. C9-UK-2A also induced ROS generation in isolated mitochondria of the S. cerevisiae cells. The addition of both a complex I inhibitor rotenone and a complex II inhibitor thenoyltrifluoroacetone reduced ROS generation induced by C9-UK-2A in the whole cells and the isolated mitochondria. The addition of the inhibitors of complex III, AA or myxothiazol, or of complex IV, KCN, did not reduce ROS generation. These results suggest that C9-UK-2A induces ROS generation due to the blockade of electron flow at complex III, thereby inhibiting the growth of S. cerevisiae in SD medium. PMID:15515888

  6. 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

  7. Phenotypic characteristics of coagulase-negative staphylococci: typing and antibiotic susceptibility.

    PubMed

    Jarløv, J O

    1999-01-01

    expensive and sophisticated equipment. Various typing schemes for S. epidermidis, i.e. typing which involves several typing methods, have been tested: lectin typing, DNA-plasmid profile analysis, antibiotic susceptibility testing, phage typing, and slime production lectin typing, antibiotic susceptibility testing, biotyping (Minibact-S), phage typing antibiotic susceptibility testing and biotyping (Minibact-S) For use as a "first line" typing scheme in the local clinical microbiology laboratory, the typing of S. epidermidis by combined antibiotic susceptibility testing and biotyping is easy to handle. Antibiotic susceptibility testing should include antibiotics from several groups of antibiotics having different resistance mechanisms. Antibiotic susceptibility among Danish CoNS-strains from blood cultures was studied. A major diversity in species distribution and antibiotic susceptibility was found between different Danish regions, for example methicillin resistant CoNS accounted for 40% in Copenhagen County and only for 21% in Northern Jutland County. Diversity in species distribution was also marked; an example of this is that 73% of the strains from Copenhagen Municipality were identified as S. epidermidis compared to only 46% in Northern Jutland County. In a study from Rigshospitalet, Copenhagen, great diversity in antibiotic susceptibility was detected between the different wards. In four wards investigated, high consumption of carbapenems, Third-generation cephalosporins, and quinolones was associated with high prevalence of methicillin resistance. Furthermore, for ciprofloxacin, ciprofloxacin-resistant CoNS-strains were practically not detected in the Neonatal Ward where ciprofloxacin is not used. In contrast to the nationwide study, glycopeptide resistance was found at Rigshospitalet: 5% of the CoNS strains were teicoplanin-resistant but all strains were vancomycin-susceptible. In both the above mentioned studies, antibiotic resistance was strongly associated with

  8. Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics

    PubMed Central

    Podoll, Jessica D.; Liu, Yongxiang; Chang, Le; Walls, Shane; Wang, Wei; Wang, Xiang

    2013-01-01

    The continuous emergence of resistant bacteria has become a major worldwide health threat. The current development of new antibacterials has lagged far behind. To discover reagents to fight against resistant bacteria, we initiated a chemical approach by synthesizing and screening a small molecule library, reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of structurally diverse natural products, many of which were isolated from plants that have been used as traditional medicine for millennia. Specifically, we adapted an evolutionarily conserved biosynthetic strategy and developed a concise and unified diversity synthesis pathway. Using this pathway, we synthesized 120 polycyclic indolines that contain 26 distinct skeletons and a wide variety of functional groups. A tricyclic indoline, Of1, was discovered to selectively potentiate the activity of β-lactam antibiotics in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin-sensitive S. aureus. In addition, we found that Of1 itself does not have antiproliferative activity but can resensitize several MRSA strains to the β-lactam antibiotics that are widely used in the clinic, such as an extended-spectrum β-lactam antibiotic amoxicillin/clavulanic acid and a first-generation cephalosporin cefazolin. These data suggest that Of1 is a unique selective resistance-modifying agent for β-lactam antibiotics, and it may be further developed to fight against resistant bacteria in the clinic. PMID:24019472

  9. 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 < 0.005). Excreted residues accounted for > 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

  10. Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics.

    PubMed

    Horsman, Geoffrey P; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S; Shen, Ben

    2013-08-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities. The inverting EHs, such as SgcF, hydrolyze an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis, whereas the retaining EHs, such as NcsF2 and KedF, hydrolyze an (S)-epoxide substrate to yield an (S)-diol in NCS and KED biosynthesis. We now report the characterization of a series of EH mutants and provide a predictive model for EH regioselectivity in the biosynthesis of the nine-membered enediyne antitumor antibiotics. A W236Y mutation in SgcF increased the retaining activity toward (S)-styrene oxide by 3-fold, and a W236Y/Q237M double mutation in SgcF, mimicking NcsF2 and KedF, resulted in a 20-fold increase in the retaining activity. To test the predictive utility of these mutations, two putative enediyne biosynthesis-associated EHs were identified by genome mining and confirmed as inverting enzymes, SpoF from Salinospora tropica CNB-440 and SgrF (SGR_625) from Streptomyces griseus IFO 13350. Finally, phylogenetic analysis of EHs revealed a familial classification according to inverting versus retaining activity. Taken together, these results provide a predictive model for vicinal diol stereochemistry in enediyne biosynthesis and set the stage for further elucidating the origins of EH regioselectivity. PMID:23844627

  11. A predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of 9-membered enediyne antitumor antibiotics

    PubMed Central

    Horsman, Geoffrey P.; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S.; Shen, Ben

    2013-01-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities – the “inverting” EH, such as SgcF, hydrolyzes an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis, while the “retaining” EHs, such as NcsF2 and KedF, hydrolyze an (S)-epoxide substrate to yield an (S)-diol in NCS and KED biosynthesis. We now report the characterization of a series of EH mutants and provide a predictive model for EH regioselectivity in the biosynthesis of the 9-membered enediyne antitumor antibiotics. A W236Y mutation in SgcF increased the retaining activity towards (S)-styrene oxide 3-fold, and a W236Y/Q237M double mutation in SgcF, mimicking NcsF2 and KedF, resulted in a 20-fold increase in the retaining activity. To test the predictive utility of these mutations, two putative enediyne biosynthesis-associated EHs were identified by genome mining and confirmed as inverting enzymes – SpoF from Salinospora tropica CNB-440 and SgrF (SGR_625) from Streptomyces griseus IFO 13350. Finally, phylogenetic analysis of EHs revealed a familial classification according to inverting versus retaining activity. Taken together, these results provide a predictive model for the vicinal diol stereochemistry in enediyne biosynthesis and set the stage for further elucidating the origins of EH regioselectivity. PMID:23844627

  12. Feasibility study of recycling cephalosporin C fermentation dregs using co-composting process with activated sludge as co-substrate.

    PubMed

    Chen, Zhiqiang; Wang, Yao; Wen, Qinxue; Zhang, Shihua; Yang, Lian

    2016-09-01

    Composting is a potential alternative for cephalosporin C fermentation dregs (CCFDs) compared with incineration process or landfill because of its advantage of recovering nutrients. In this research, CCFDs and activated sludge (AS) were co-composted to analyze the feasibility of recycling the nutrients in CCFDs. A pilot-scale aerobic composting system with an auto-control system was used in this research, and the maturity and security of the compost product were evaluated. The temperature of the composting mixtures was maintained above 55°C for more than 3 days during the composting, indicating that co-composting of CCFDs and AS could reach the compost maturity standard, and the seeds germination index (GI) increased from 17.61% to 68.93% by the end of the composting process (28 days). However, the degradation rate of cephalosporin C (CPC) was only 6.58% during the composting process. Monitoring the quality of antibiotic resistance genes (ARGs) in the composts showed that the log copy of blaTEM in the composts increased from 2.15 in the initial phase to 6.37 after 28 days. Long-term investigation of CPC degradation and ARGs variation was conducted for the composts; CPC could still be detected after the maturity phases. A removal efficiency of 49.10% could be achieved in 110 days, while the log copy of ARGs increased to 7.93. Although a higher GI value (>80.00%) was observed, the risk of recycling the CCFDs compost product into land is still high. PMID:26828961

  13. Antibiotics Quiz

    MedlinePlus

    ... Viruses b) Bacteria c) Viruses and Bacteria 2. Bacteria are germs that cause colds and flu. a) ... The Flu c) Cold d) Strep Throat 4. Bacteria that cause infections can become resistant to antibiotics. ...

  14. [Antibiotic pharmacoeconomics].

    PubMed

    Jahnz-Rózyk, Karina

    2008-11-01

    Today more than ever, doctors in the ambulatory care and hospitals must effectively manage the use of antibiotics to control costs and preserve their usefulness. To achieve this goal, antibiotic management must evolve from simplistic antibiotic cost containment to more complex, appropriate use program that are founded on clinical outcomes-based pharmacoeconomic analyses. The successful application of pharmacoeconomic principles to antimicrobial therapy requires maximizing therapeutic effectiveness while minimizing costs, with the primary on pharmacokinetic considerations. This article reviews the various pharmacoeconomic factors that affect antibiotic costs in relation to patients and institutions. Cost-effectiveness studies of macrolides in pulmonary infections are presented in this study to illustrate the utility of these analyses. PMID:19177784

  15. Antibiotic Use and Need for Antimicrobial Stewardship in Long-Term Care

    PubMed Central

    Wu, Lisa Dong-Ying; Walker, Sandra A N; Elligsen, Marion; Palmay, Lesley; Simor, Andrew; Daneman, Nick

    2015-01-01

    Background: Antimicrobial stewardship may be important in long-term care facilities because of unnecessary or inappropriate antibiotic use observed in these residents, coupled with their increased vulnerability to health care–associated infections. Objectives: To assess antibiotic use in a long-term care facility in order to identify potential antimicrobial stewardship needs. Methods: A retrospective descriptive study was conducted at the Veterans Centre, a long-term care facility at Sunnybrook Health Sciences Centre, Toronto, Ontario. All residents taking one or more antibiotics (n = 326) were included as participants. Antibiotic-use data for patients residing in the facility between April 1, 2011, and March 31, 2012, were collected and analyzed. Results: Totals of 358 patient encounters, 835 antibiotic prescriptions, and 193 positive culture results were documented during the study period. For 36% (302/835) of antibiotic prescriptions, the duration was more than 7 days. Cephalosporins (30%; 251/835) and fluoroquinolones (28%; 235/835) were the most frequently prescribed antibiotic classes. Urine was the most common source of samples for culture (60%; 116/193). Conclusions: Characteristics of antimicrobial use at this long-term care facility that might benefit from further evaluation included potentially excessive use of fluoroquinolones and cephalosporins and potentially excessive duration of antibiotic use for individual patients. PMID:26715780

  16. 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, Célia 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

  17. Cephalosporin-induced hypoprothrombinemia: is the N-methylthiotetrazole side chain the culprit?

    PubMed Central

    Agnelli, G; Del Favero, A; Parise, P; Guerciolini, R; Pasticci, B; Nenci, G G; Ofosu, F

    1986-01-01

    The reported high incidence of vitamin-K-reversible hypoprothrombinemia associated with the new beta-lactamase-stable cephalosporins prompted us to evaluate the effect on hemostasis of three cephalosporins (cefamandole, ceftriaxone, and ceftazidime) in 30 patients with serious infections. Cefamandole and ceftriaxone, both containing a sulfhydryl group, induced a significant and similar prolongation of prothrombin time and decrease in factor VII activity. Ceftazidime, in contrast, had no effect on these two parameters. PMID:3729364

  18. 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

  19. Generating Elastic, Biodegradable Polyurethane/Poly(lactide-co-glycolide) Fibrous Sheets with Controlled Antibiotic Release via Two-Stream Electrospinning

    PubMed Central

    Hong, Yi; Fujimoto, Kazuro; Hashizume, Ryotaro; Guan, Jianjun; Stankus, John J.; Tobita, Kimimasa; Wagner, William R.

    2010-01-01

    Damage control laparotomy is commonly applied to prevent compartment syndrome following trauma but is associated with new risks to the tissue, including infection. To address the need for biomaterials to improve abdominal laparotomy management, we fabricated an elastic, fibrous composite sheet with two distinct submicrometer fiber populations: biodegradable poly(ester urethane) urea (PEUU) and poly(lactide-co-glycolide) (PLGA), where the PLGA was loaded with the antibiotic tetracycline hydrochloride (PLGA-tet). A two-stream electrospinning setup was developed to create a uniform blend of PEUU and PLGA-tet fibers. Composite sheets were flexible with breaking strains exceeding 200%, tensile strengths of 5–7 MPa, and high suture retention capacity. The blending of PEUU fibers markedly reduced the shrinkage ratio observed for PLGA-tet sheets in buffer from 50% to 15%, while imparting elastomeric properties to the composites. Antibacterial activity was maintained for composite sheets following incubation in buffer for 7 days at 37 °C. In vivo studies demonstrated prevention of abscess formation in a contaminated rat abdominal wall model with the implanted material. These results demonstrate the benefits derivable from a two-stream electrospinning approach wherein mechanical and controlled-release properties are contributed by independent fiber populations and the applicability of this composite material to abdominal wall closure. PMID:18318501

  20. The pharmacokinetics of the oral cephalosporins--a review.

    PubMed

    Wise, R

    1990-12-01

    The pharmacokinetics of the older and more recent oral cephalosporins are reviewed. With the exception of cefadroxil the older agents (cephalexin, cephradine and cefaclor) have serum elimination half-lives of less than or equal to 1 h and hence have to be administered three to four times daily. The urinary recovery of these agents is high (greater than 80% of oral dose) with the exception of cefaclor (54%). Cefaclor is also chemically unstable. The newer agents can be divided into those that are prodrugs (cefpodoxime proxetil and cefuroxime axetil) and compounds that are absorbed as such (cefixime, cefprozil and ceftibuten). They all have half-lives greater than 1.25 h and can be given once or twice daily. The penetration of these agents into an inflammatory exudate was studied and found to be cefixime 132%, ceftibuten 113%, cefpodoxime 104%, cefuroxime 92% and cefprozil 79% of the serum concentration. The penetration of cefpodoxime and cefixime into the respiratory tract was also studied; the mean percentage bronchial mucosal penetration was 52% for the former and 38% for cefixime. The urinary recovery of these newer agents (with the exception of ceftibuten) tends to be less than that of the earlier agents. There was a relationship between the serum elimination half-life of these agents and the degree of tissue penetration, those agents with longer half-lives penetrating to a greater extent. PMID:2292525

  1. Biological activity of BO-1236, a new antipseudomonal cephalosporin.

    PubMed Central

    Nakagawa, S; Sanada, M; Matsuda, K; Hazumi, N; Tanaka, N

    1987-01-01

    BO-1236, a new cephalosporin having an N-methyl-5,6-dihydroxyisoindolinium moiety on the 3-methylene of the cephem, showed potent activity against gram-negative organisms, including Pseudomonas aeruginosa. The in vitro activity of BO-1236 was superior or comparable to that of ceftazidime, cefotaxime, and cefoperazone in susceptibility tests with clinical isolates. BO-1236 was significantly more active than ceftazidime against P. aeruginosa strains susceptible or resistant to ceftazidime or gentamicin or both. MBCs were usually close to MICs, both of which were influenced by inoculum size to about the same degree as those of the other beta-lactams. BO-1236 was stable to all types of beta-lactamases except type I oxyiminocephalosporin-hydrolyzing enzyme, by which BO-1236 was slightly hydrolyzed. BO-1236 showed protective activity superior to that of ceftazidime and cefotaxime in experimental infections in mice caused by two strains of P. aeruginosa and showed activity comparable to that of ceftazidime and cefotaxime against other gram-negative bacterial infections. PMID:3116919

  2. 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 Suzuki–Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time. PMID:24328139

  3. Antibiotic concentration in human wound fluid after intravenous administration.

    PubMed Central

    Bagley, D H; Mac Lowry, J; Beazley, R M; Gorschboth, C; Ketcham, A S

    1978-01-01

    Since the wound is the most common focus of infection in the surgical patient, adequate levels of antibiotic within the wound ar essential. This study examines the concentrations of antibiotic achieved in human wounds. Fluid was collected at timed intervals on the first postoperative day from the wounds of 56 patients receiving antibiotics after regional lymph node dissection. Antibiotic concentration was determined by bioassay. Six antibiotics were studied: cephalothin, cefazolin, cephapirin, oxacillin, ampicillin and clindamycin. The cephalosporins and penicillins showed similar patterns of appearance in the wound fluid. The peak level occurred early (1--1 1/2 hours) with subsequent slow decrease. Clindamycin produced nearly constant levels in wound fluid. The concentration of each antibiotic in wound fluid surpassed the serum levels after 2.5 hours. At the dosages studied each antibiotic produced wound fluid concentrations greater than the MIC for most susceptible organisms. Higher doses provided higher wound fluid levels. The rate of appearance and the levels achieved should be considered in the choice of antibiotics in the surgical subject. Images Fig. 1. PMID:686888

  4. 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

  5. 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

  6. New antibiotic agents for bloodstream infections.

    PubMed

    Vergidis, Paschalis I; Falagas, Matthew E

    2008-11-01

    Infections due to multidrug-resistant pathogens have shown a dramatic worldwide increase in prevalence. Bloodstream infections (BSIs) represent an important cause of morbidity and mortality in hospitalised patients. Research in the field led to the introduction of several novel antibiotic agents in the fight against bacterial pathogens. New antibiotics used against Gram-positive bacteria, mainly meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, include daptomycin, linezolid, quinupristin/dalfopristin and semisynthetic lipoglycopeptides. Among the Gram-negative bacteria, extended-spectrum beta-lactamase-producing Enterobacteriaceae as well as highly resistant Pseudomonas and Acinetobacter isolates are of particular concern. Doripenem is a recently approved carbapenem. Polymyxins are reconsidered as valuable therapeutic options for Gram-negative infections. Tigecycline, a glycylcycline, and ceftobiprole, a novel cephalosporin under investigation, have activity both against Gram-positive and Gram-negative organisms. In addition to the above agents, alternative treatment approaches that require further investigation have also been introduced into clinical practice. These include antibiotic lock therapy and continuous intravenous administration of antibiotics. In this article, we review the above treatment options for BSIs based on current clinical evidence. Comparative trials specifically focusing on patients with bacteraemia were generally not performed; however, a proportion of patients from the reported studies did have bacteraemia. PMID:18723329

  7. Update on antibiotics in ocular infections.

    PubMed

    Leopold, I H

    1985-07-15

    Each year, new antimicrobials are found or synthesized in an effort to improve the chance of overcoming infections. In the early 1950s, the only antibiotic available for ocular use was penicillin. Today, ophthalmologists can make a choice from a large selection of antibiotics for ocular infections. The majority of antibiotics have been literally unearthed, since worldwide soil surveys may have been the means of their discovery. In addition, synthetic derivatives of penicillin, cephalosporins, aminoglycosides, and tetracyclines, as well as drugs against tuberculosis and fungi, have become available, and new names have been added to the already bewildering list of less frequently used sulfonamides. However, it takes several years to appreciate the impact of new agents and the continued contribution of older ones. Constant reevaluation is mandatory. The real benefits as well as the untoward effects of a new antimicrobial agent may not be known until several years after the clinical introduction. In addition to approaching infection from the viewpoint of the offending organism and a specific antibiotic to address this organism, one may also approach this problem from the host's immunity. Until now, we have relied largely on the corticosteroids, but one must also consider various nonsteroidal anti-inflammatory agents and, even more importantly, the development of drugs to enhance the host's natural immunity. PMID:3925785

  8. In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci.

    PubMed

    Jones, Ronald N; Deshpande, Lalitagauri M; Mutnick, Alan H; Biedenbach, Douglas J

    2002-12-01

    pneumoniae. BAL9141 demonstrated excellent activity against many tested pathogens displaying various resistance phenotypes, and should be particularly valuable in the treatment of MRSA as well as for drug-resistant streptococci, while maintaining a spectrum resembling a 'third-generation' cephalosporin against other clinically important species. PMID:12461013

  9. Curing bacteria of antibiotic resistance: reverse antibiotics, a novel class of antibiotics in nature.

    PubMed

    Hiramatsu, Keiichi; Igarashi, Masayuki; Morimoto, Yuh; Baba, Tadashi; Umekita, Maya; Akamatsu, Yuzuru

    2012-06-01

    By screening cultures of soil bacteria, we re-discovered an old antibiotic (nybomycin) as an antibiotic with a novel feature. Nybomycin is active against quinolone-resistant Staphylococcus aureus strains with mutated gyrA genes but not against those with intact gyrA genes against which quinolone antibiotics are effective. Nybomycin-resistant mutant strains were generated from a quinolone-resistant, nybomycin-susceptible, vancomycin-intermediate S. aureus (VISA) strain Mu 50. The mutants, occurring at an extremely low rate (<1 × 10(-11)/generation), were found to have their gyrA genes back-mutated and to have lost quinolone resistance. Here we describe nybomycin as the first member of a novel class of antibiotics designated 'reverse antibiotics'. PMID:22534508

  10. Generation of a safety enhanced Salmonella Gallinarum ghost using antibiotic resistance free plasmid and its potential as an effective inactivated vaccine candidate against fowl typhoid.

    PubMed

    Jawale, Chetan V; Chaudhari, Atul A; Lee, John Hwa

    2014-02-19

    A safety enhanced Salmonella Gallinarum (SG) ghost was constructed using an antibiotic resistance gene free plasmid and evaluated its potential as fowl typhoid (FT) vaccine candidate. The antibiotic resistance free pYA3342 plasmid possesses aspartate semialdehyde dehydrogenase gene which is complimentary to the deletion of the chromosomal asd gene in the bacterial host. This plasmid was incorporated with a ghost cassette containing the bacteriophage PhiX174 lysis gene E, designated as pJHL101. The plasmid pJHL101 was transformed into a two virulence genes-deleted SG. The SG ghosts with tunnel formation and loss of cytoplasmic contents were observed by scanning electron microscopy and transmission electron microscopy. The cell viability of the culture solution was decreased to 0% at 24h after the induction of gene E expression by an increase in temperature from 37°C to 42°C. The safety and protective efficacy of the SG ghost vaccine was further examined in chickens which were divided into three groups: group A (non-immunized control), group B (orally immunized), and group C (intramuscularly immunized). The birds were immunized at 7d of age. No clinical symptoms associated with FT such as anorexia, depression and greenish diarrhea were observed in the immunized chickens. Upon challenge with a virulent SG strain at 3 week post-immunization, the chickens immunized with the SG ghost via various routes were efficiently protected, as shown by significantly lower mortality and post-mortem lesions in comparison with control group. In addition, all the immunized chickens showed significantly higher antibody responses accompanied by a potent antigen-specific lymphocyte proliferative response along with significantly increased numbers of CD4⁺ and CD8⁺ T lymphocytes. Overall, our results provide a promising approach of generating SG ghosts using the antibiotic resistance free plasmid in order to prepare a non-living bacterial vaccine candidate which could be

  11. Antibiotic prescribing and expenditures in outpatient adults in Greece, 2010 to 2013: evidence from real-world practice.

    PubMed

    Kourlaba, Georgia; Gkrania-Klotsas, Effrossyni; Kourkouni, Eleni; Mavrogeorgos, Georgios; Zaoutis, Theoklis E

    2016-06-30

    We provide a representative analysis of antibiotic prescribing, identify factors associated with broad-spectrum antibiotic prescribing and assess the costs associated with antibiotic use in adult outpatients in Greece. Outpatient antibiotic prescriptions for patients older than 19 years between 2010 and 2013 in Greece were extracted from the IMS Health Xponent database. Prescribing rate and total cost for prescribed antibiotics were calculated. Multivariate logistic regression was used to identify factors related to broad-spectrum antibiotic prescribing. More than 20 million antibiotics were prescribed during the study period, an annual rate of 768 prescribed antibiotics per 1,000 adults. Overall, 33.5% of antibiotics were prescribed for acute respiratory tract infections (ARTIs) for which antibiotics are often not indicated. Macrolides (29.9%), cephalosporins (26.9%) and fluoroquinolones (21.0%) were the most commonly prescribed antibiotic classes. The majority (89.0%) of antibiotics were broad-spectrum. Antibiotic expenditures were approximately EUR 185 million during the study period. Factors associated with broad-spectrum prescribing included older patient age, specialty pulmonologists or otorhinolaryngologists, training in eastern Europe, diagnosis of ARTI, acute diagnosis, and first episode of disease. Broad-spectrum antibiotic prescribing for ARTIs is common in adult Greek outpatients and frequently inappropriate. These data indicate the need for initiatives aiming to control antibiotic prescribing. PMID:27390126

  12. Seasonality and Physician-related Factors Associated with Antibiotic Prescribing: A Cross-sectional Study in Isfahan, Iran

    PubMed Central

    Safaeian, Leila; Mahdanian, Ali-Reza; Salami, Solmaz; Pakmehr, Farzaneh; Mansourian, Marjan

    2015-01-01

    Background: Irrational antibiotic prescribing as a global health problem has a major influence on medical care quality and healthcare expenditure. This study was aimed to determine the pattern of antibiotic use and to assess the seasonality and physician-related factors associated with variability in antibiotic prescribing in Isfahan province of Iran. Methods: This cross-sectional survey was conducted on all prescriptions issued by general physicians from rural and urban areas in 2011. Associations between season of prescribing and physician-related variables including gender, practice location and time since graduation with antibiotic prescriptions and also the pattern of antibiotic prescribing were assessed using Chi-square tests and multiple logistic regression models. Results: Of the 7439709 prescriptions issued by 3772 general practitioners, 51% contained at least one antibiotic. Penicillins were the most frequently prescribed antibiotics, followed by cephalosporins and macrolides. Over-prescription of penicillins was associated with female gender (odds ratio [OR], 2.61; 95% confidence interval [CI] 2.13–3.19) and with moderate duration of time in practice (10–20 years) (OR, 1.42; 95% CI 1.14–1.76). Higher rates of cephalosporins prescription were observed in urban areas than rural areas and by male physicians. Seasonal peak was detected for penicillins and cephalosporins prescriptions in autumn. Conclusions: These findings showed the widespread use of antibiotics by general practitioners that was associated with the physicians’ gender, time since graduation and practice location and also season of prescribing. More researches are needed on other factors related to the overprescribing of antibiotics and they could be used to project educational programs for improvement of antibiotic prescribing quality in our country. PMID:25789136

  13. A questionnaire-based survey to ascertain the views of clinicians regarding rational use of antibiotics in teaching hospitals of Kolkata

    PubMed Central

    Chatterjee, Dattatreyo; Sen, Sukanta; Begum, Sabnam Ara; Adhikari, Anjan; Hazra, Avijit; Das, Anup Kumar

    2015-01-01

    Objectives: The objective was to assess the views of clinicians in teaching hospitals of Kolkata regarding the use of antibiotics in their own hospitals, focusing on perceived misuse, reasons behind such misuse and feasible remedial measures. Materials and Methods: A total of 200 clinicians from core clinical disciplines was approached in six teaching hospitals of Kolkata through purposive sampling. A structured, validated questionnaire adopted from published studies and modified to suit the responding population was completed by consenting respondents through face-to-face interaction with a single interviewer. Respondents were free to leave out questions they did not wish to answer. Results: Among 130 participating clinicians (65% of approached), all felt that antibiotic misuse occurs in various hospital settings; 72 (55.4% of the respondents) felt it was a frequent occurrence and needed major rectification. Cough and cold (78.5%), fever (65.4%), and diarrhea (62.3%) were perceived to be the commonest conditions of antibiotic misuse. About half (50.76%) felt that oral preparations were more misused compared to injectable or topical ones. Among oral antibiotics, co-amoxiclav (66.9%) and cefpodoxime (63.07%) whereas among parenteral ones, ceftriaxone and other third generation cephalosporins (74.6%) followed by piperacillin-tazobactam (61.5%) were selected as the most misused ones. Deficient training in rational use of medicines (70.7%) and absence of institutional antibiotic policy (67.7%) were listed as the two most important predisposing factors. Training of medical students and interns in rational antibiotic use (78.5%), implementation of antibiotic policy (76.9%), improvement in microbiology support (70.7%), and regular surveillance on this issue (64.6%) were cited as the principal remedial measures. Conclusions: Clinicians acknowledge that the misuse of antibiotics is an important problem in their hospitals. A system of clinical audit of antibiotic usage

  14. Origin of Glycine from Acid Hydrolysis of the β-Lactam Antibiotic A16886B

    PubMed Central

    Brannon, D. R.; Mabe, J. A.; Ellis, R.; Whitney, J. G.; Nagarajan, R.

    1972-01-01

    Structural analysis of two new β-lactam antibiotics, A16884A and A16886B, indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and α-aminoadipic acid. However, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolysis of cephalosporin C under the same conditions. Samples of A16886B-14C-6 and A16886B-14C-8 were prepared by the addition of cysteine-14C-3 and cystine-14C-1 to fermentations of Streptomyces clavuligerus. The specific activity of glycine obtained from hydrolysis of A16886B-14C-6 was considerably higher than that from hydrolysis of A16886B-14C-8. An explanation for the difference in amounts of glycine obtained from hydrolysis of these antibiotics is discussed. PMID:5045470

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

    PubMed

    Li, Xiaolin; Zheng, Wei; Machesky, Michael L; Yates, Scott R; Katterhenry, Michael

    2011-09-28

    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 understand the potential contamination of the antibiotic in the environment, the degradation kinetics and mechanisms of ceftiofur in solutions blended with and without the recycled water derived from a beef farm were investigated. The transformation of ceftiofur in aqueous solutions in the presence of the CAFO recycled water was the combined process of hydrolysis and biodegradation. The total degradation rates of ceftiofur at 15 °C, 25 °C, 35 °C, and 45 °C varied from 0.4-2.8×10(-3), 1.4-4.4×10(-3), 6.3-11×10(-3), and 11-17×10(-3) h(-1), respectively, in aqueous solutions blended with 1 to 5% CAFO recycled water. Hydrolysis of ceftiofur increased with incubation temperature from 15 to 45 °C. The biodegradation rates of ceftiofur were also temperature-dependent and increased with the application amounts of the recycled CAFO water. Cef-aldehyde and desfuroylceftiofur (DFC) were identified as the main biodegradation and hydrolysis products, respectively. This result suggests that the primary biodegradation mechanism of ceftiofur was the cleavage of the β-lactam ring, while hydrolytic cleavage occurred at the thioester bond. Unlike DFC and ceftiofur, cef-aldehyde does not contain a β-lactam ring and has less antimicrobial activity, indicating that the biodegradation of ceftiofur in animal wastewater may mitigate the potentially adverse impact of the antibiotic to the environment. PMID:21863813

  16. Hospital Acquired Pneumonia Due to Achromobacter spp. in a Geriatric Ward in China: Clinical Characteristic, Genome Variability, Biofilm Production, Antibiotic Resistance and Integron in Isolated Strains

    PubMed Central

    Liu, Chao; Pan, Fei; Guo, Jun; Yan, Weifeng; Jin, Yi; Liu, Changting; Qin, Long; Fang, Xiangqun

    2016-01-01

    Background: Hospital-acquired pneumonia (HAP) due to Achromobacter has become a substantial concern in recent years. However, HAP due to Achromobacter in the elderly is rare. Methods: A retrospective analysis was performed on 15 elderly patients with HAP due to Achromobacter spp., in which the sequence types (STs), integrons, biofilm production and antibiotic resistance of the Achromobacter spp. were examined. Results: The mean age of the 15 elderly patients was 88.8 ± 5.4 years. All patients had at least three underlying diseases and catheters. Clinical outcomes improved in 10 of the 15 patients after antibiotic and/or mechanical ventilation treatment, but three patients had chronic infections lasting more than 1 year. The mortality rate was 33.3% (5/15). All strains were resistant to aminoglycosides, aztreonam, nitrofurantoin, and third- and fourth-generation cephalosporins (except ceftazidime and cefoperazone). Six new STs were detected. The most frequent ST was ST306. ST5 was identified in two separate buildings of the hospital. ST313 showed higher MIC in cephalosporins, quinolones and carbapenems, which should be more closely considered in clinical practice. All strains produced biofilm and had integron I and blaOXA-114-like. The main type was blaOXA-114q. The variable region of integron I was different among strains, and the resistance gene of the aminoglycosides was most commonly inserted in integron I. Additionally, blaPSE-1 was first reported in this isolate. Conclusion: Achromobacter spp. infection often occurs in severely ill elders with underlying diseases. The variable region of integrons differs, suggesting that Achromobacter spp. is a reservoir of various resistance genes. PMID:27242678

  17. Comparison of the secondary metabolites in two scales of cephalosporin C (CPC) fermentation and two different post-treatment processes.

    PubMed

    Cao, Ying-Xiu; Lu, Hua; Qiao, Bin; Chen, Yao; Yuan, Ying-Jin

    2013-01-01

    Cephalosporin C (CPC) is the precursor of a class of antibiotics that were more effective than traditional penicillins. CPC production is performed mainly through fermentation by Acremonium chrysogenum, whose secondary metabolism was sensitive to the environmental changes. In the present work, secondary metabolites were measured by ion-pair reversed-phase liquid chromatography tandemed with hybrid quadrupole time-of-flight mass spectrometry, and the disparity of them from two scales of CPC fermentations (pilot and industrial) and also two different post-treatment processes (oxalic acid and formaldehyde added and control) were investigated. When fermentation size was enlarged from pilot scale (50 l) to industrial scale (156,000 l), the remarkable disparities of concentrations and changing trends of the secondary metabolites in A. chrysogenum were observed, which indicated that the productivity of CPC biosynthesis was higher in the large scale of fermentation. Three environmental factors were measured, and the potential reasons that might cause the differences were analyzed. In the post-treatment process after industrial fermentation, the changes of these secondary metabolites in the tank where oxalic acid and formaldehyde were added were much less than the control tank where none was added. This indicated that the quality of the final product was more stable after the oxalic acid and formaldehyde were added in the post-treatment process. These findings provided new insight into industrial CPC production. PMID:23053347

  18. 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

  19. 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

  20. 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 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

  1. 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

  2. Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations†

    PubMed Central

    Tomberg, Joshua; Unemo, Magnus; Davies, Christopher; Nicholas, Robert A

    2010-01-01

    Mutations in penicillin-binding protein 2 (PBP 2) encoded by mosaic penA alleles are critical for intermediate resistance to the expanded-spectrum cephalosporins ceftriaxone and cefixime in Neisseria gonorrhoeae. Three of the ~60 mutations present in mosaic alleles of penA, G545S, I312M, and V316T, have been reported to be responsible for increased resistance, especially to cefixime (Takahata et al. 2006. Antimicrob Agents Chemother 50:3638-45). However, we observed that the minimum inhibitory concentrations (MICs) of penicillin, ceftriaxone, and cefixime for a wild type strain (FA19) containing a penA gene with these three mutations increased only 1.5-, 1.5-, and 3.5-fold, respectively. In contrast, when these three mutations in a mosaic penA allele (penA35) were reverted back to wild type and the gene transformed into FA19, the MICs of the three antibiotics were reduced to near wild type levels. Thus, these three mutations display epistasis, in that their capacity to increase resistance to β-lactam antibiotics is dependent on the presence of other mutations in the mosaic alleles. We also identified an additional mutation, N512Y, that contributes to decreased susceptibility to expanded-spectrum cephalosporins. Finally, we investigated the effects of a mutation (A501V) currently found only in non-mosaic penA alleles on decreased susceptibility to ceftriaxone and cefixime, under the expectation that this mutation may arise in mosaic alleles. Transfer of the mosaic penA35 allele containing an A501V mutation into FA6140, a chromosomally mediated penicillin-resistant isolate, increased the MICs of ceftriaxone (0.4 μg/ml) and cefixime (1.2μg/ml) to levels above their respective breakpoints. The proposed structural mechanisms of these mutations are discussed in light of the recently published structure of PBP 2. PMID:20704258

  3. 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

  4. New antimicrobial molecules and new antibiotic strategies.

    PubMed

    Rodríguez de Castro, Felipe; Naranjo, Olga Rajas; Marco, Javier Aspa; Violán, Jordi Solé

    2009-04-01

    Drug options for treatment of infections are increasingly limited. The pharmaceutical industry has found it difficult to discover new antimicrobial agents, and only two novel classes of antibiotics, the oxazolidinones and the cyclic lipopeptides, have entered the market since the late 1960s. Few new agents have reached the market in the last decade with potential interest for community-acquired pneumonia (CAP) treatment, including linezolid (the first oxazolidinone in clinical use), new fluoroquinolones, cefditoren, ertapenem, and telithromycin. Agents currently in clinical development include other novel quinolones and ketolides, broad-spectrum cephalosporin derivatives, faropenem, several glycopeptides, and iclaprim. Other molecules are considered to be promising candidates for the future. In addition to the foregoing agents, alternative treatment approaches have also been introduced into clinical practice, which include the administration of the appropriate antimicrobials in a timely manner and the consideration of the pharmacokinetic-pharmacodynamic properties of the agent(s). PMID:19296416

  5. Randomized controlled trial on the safety of intracameral cephalosporins in cataract surgery

    PubMed Central

    Lam, Philip TH; Young, Alvin L; Cheng, Lulu L; Tam, Patrick MK; Lee, Vincent YW

    2010-01-01

    Objective: To compare the safety profiles of intracameral cephalosporins in cataract surgery. Patients and methods: In this controlled trial, 129 patients were randomized to one of four groups to receive 1 mg of one of three cephalosporins – cefazolin, cefuroxime, or ceftazidime, or normal saline – given intracamerally during cataract surgery. Central endothelial cell density (ECD) and retinal center point thickness (CPT) were determined by specular microscopy and ocular coherence tomography, respectively, before and at 3 months after surgery. Results: There were no statistical significant differences in the changes of ECD and CPT between eyes receiving intracameral cephalosporin and control. Conclusion: The use of intracameral cefazolin, cefuroxime, or ceftazidime (1 mg in 0.1-mL solution) at the time of cataract surgery had no significant effect on ECD and CPT postoperatively. PMID:21191447

  6. Morphological, physiological and enzymatic characteristics of cephalosporin acylase-producing Arthrobacter strain 45-8A.

    PubMed

    Zhang, Q J; Xu, W X

    1993-01-01

    A bacterial strain producing cephalosporin acylases was isolated from soil. The morphological and physiological properties of this strain suggest that it belongs to the genus Arthrobacter, and the isolate was therefore designated Arthrobacter strain 45-8A. Substrate specificity of the enzyme was examined. The enzyme can convert both cephalosporin acid to 7-aminocephalosporanic acid. An interesting feature of the acylases is their temperature-dependent regulation. Activity of acylases was detected in strain 45-8A grown at temperature below 30 degrees C, but was not observed at higher temperature. Arthrobacter strain 45-8A did not exhibit beta-lactamase activity, even though its resistance to cephalosporin C was very strong (> 2000 micrograms/ml). This is quite beneficial for its application in the manufacture of 7-aminocephalosporanic acid. PMID:8484708

  7. 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

  8. [Synthesis of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins].

    PubMed

    Fan, H J; Duan, T H; Li, M H

    1989-01-01

    Seventeen derivatives of 7-(4,7-di-substituted coumarin-3-acetamido)cephalosporins were synthesized with acid chloride method, Vilsmeier reagent method and mixed anhydride method. Isolation and purification were fulfilled with Sephadex LH-20 column chromatography and centrifugal-TLC technique. Their chemical structures were identified by elemental analysis, IR and 1HNMR spectrum. The preliminary antibacterial activity tests showed that these cephalosporin derivatives exhibited good activity against Gram-positive bacteria and individual Gram-negative bacteria. Further experiments in pharmacology will be made. PMID:2816372

  9. 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

  10. Facts about Antibiotic Resistance

    MedlinePlus

    ... Trends and Cost Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance has been called one of the world’s most ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children is of particular concern ...

  11. Five-year assessment of causative agents and antibiotic resistances in urinary tract infections

    PubMed Central

    Çoban, Bayram; Ülkü, Nesrin; Kaplan, Halit; Topal, Burhan; Erdoğan, Haluk; Baskın, Esra

    2014-01-01

    Aim: To show the distribution and changes of causative agents of urinary tract infections in children and resistance rates by years and select the most appropriate antibiotics. Material and Methods: In this study, the Başkent University Alanya Research and Application Hospital automation system microbiology recording book was screened retrospectively. Growth of a single microorganism above 105 colonies (cfu/mL) was included in the assessment. Throughout the study, 10 691 urinary cultures were studies and growth was found in 392 (3.7%). Results: Three hundred and nine (78.8%) of the samples with growth belonged to girls. Growth was found in the neonatal period in 32 patients (8.2%). The most commonly isolated microorganism was Escherichia coli (E. coli) which was found in 68.4% of the patients. Klebsiella spp. were found with a rate of 12.0%; Enterobacter spp. were found with a rate of 10.7% and proteus spp. were found with a rate of 5.1%. Resistance to cefalotin (62.1%), trimethoprim-sulfamethoxasole (43.1%), amoxycillin-clavulanate (34.8%), ampicillin (30.4%), cefixim (26.3%) and nitrofurantoin (3.6%) was found in E. coli species. The antibiotic which had the highest resistance rate was ampicillin with a rate of 93.2% for klebsiella and 83.4% for enterobacter. Klebsiella spp. were the most commonly grown pathogens in newborns (40.6%). In a follow-up period of 5 years, the resistance of E. coli to amoxycillin-clavulanate regressed from 40.3% to 31.3%, while the resistance to trimethoprim-sulfamethoxasole (TMP-SMX) regressed from 45.6% to 34.7%. Conclusions: A high resistance against first-generation cephalosporins, ampicillin, amoxycillin-clavulanate and TMP-SMX which are the first-line antibiotics in childhood urinary tract infections was found. Carbapenem (meropenem, imipenem) resistance was not found in our center. Nitrofurantoin, aminoglycosides and cefixime can be recommended for empirical treatment in our hospital because of low resistance. Antibiotic

  12. 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

  13. 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

  14. 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

  15. The in vitro activity of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis.

    PubMed

    Chen, C H; Yang, M H; Lin, J S; Lee, Y C; Perng, R P

    1995-04-01

    Although there are reports that the addition of a beta-lactamase inhibitor to ampicillin or amoxicillin greatly improves their in vitro activity against M. tuberculosis, there are no written reports about the antituberculosis effects of beta-lactamase inhibitors in combination with cephalosporins against M. tuberculosis. In this report, we have determined the minimal inhibitory concentrations (MIC) of 5 cephalosporins with or without combination with beta-lactamase inhibitor against M. tuberculosis strains isolated from patients before antituberculosis treatment and checked the production of beta-lactamase by bacteria before this procedure. Four strains of M. tuberculosis were contaminated during the experiment, and all the other 16 strains hydrolyzed the nitrocefin disc, thus indicating a beta-lactamase producer. The MICs of cephalosporins alone against M. tuberculosis were 200-400 micrograms/ml for ceforanide, 100-400 micrograms/ml for cephapirin, 400-1600 micrograms/ml for cefamandole, 200-1600 micrograms/ml for cefotaxime, and 800-1600 micrograms/ml for ceftriaxone. After adding the equimolar concentrations of sulbactam, the MICs were reduced to 100-200 micrograms/ml for ceforanide, 12.5-100 micrograms/ml for cephapirin, 100-400 micrograms/ml for cefamandole, 25-200 micrograms/ml for cefotaxime, and 100-800 micrograms/ml for ceftriaxone. We concluded that sulbactam enhanced the antituberculosis effect of cephalosporins. PMID:7624446

  16. Lack of relevance of kinetic parameters for exocellular DD-peptidases to cephalosporin MICs.

    PubMed Central

    Boyd, D B; Ott, J L

    1986-01-01

    MICs of a set of cephalosporins against a variety of gram-positive and gram-negative pathogens showed no strong correlations with the rate at which these inhibitors acylate or are deacylated by beta-lactam-sensitive DD-peptidases excreted by Streptomyces sp. strain R61 and Actinomadura sp. strain R39. PMID:3729340

  17. Risk factors for occurrence of cephalosporin-resistant Escherichia coli in Norwegian broiler flocks.

    PubMed

    Mo, Solveig Sølverød; Kristoffersen, Anja Bråthen; Sunde, Marianne; Nødtvedt, Ane; Norström, Madelaine

    2016-08-01

    A longitudinal study of 27 broiler farms including 182 broiler flocks was performed to determine risk factors for occurrence of cephalosporin-resistant Escherichia coli in Norwegian broiler flocks. Information regarding possible risk factors was collected by an online questionnaire and by samples obtained from broiler and parent flocks during the study period. Additional information was provided by the broiler production company. The prevalence of cephalosporin-resistant E. coli in parent flocks and broiler flocks sampled in the study was estimated. Cephalosporin-resistant E. coli was detected in 13.8% of the parent flocks and 22.5% of the broiler flocks included in the study. A multivariable generalized linear model was used to estimate risk factors. The risk for occurrence of cephalosporin-resistant E. coli was associated with the status of the previous flock in the broiler house (odds ratio=12.7), number of parent flocks supplying the broiler flock with day-old chickens (odds ratio=6.3), routines for disinfection of floor between production cycles (odds ratio=0.1), and transport personnel entering the room where the broilers are raised (odds ratio=9.3). Our findings highlights that implementation of a high level of biosecurity with a minimal number of people entering the broiler house during production cycles, as well as rigorous cleaning and disinfection routines between production cycles will contribute to a decrease in the occurrence of cephalosporin-resistant E. coli in broiler flocks provided that there is no selection pressure from antimicrobial use in the broiler production. PMID:27435654

  18. Bacteriology of Naja atra Snakebite Wound and Its Implications for Antibiotic Therapy.

    PubMed

    Mao, Yan-Chiao; Liu, Po-Yu; Hung, Dong-Zong; Lai, Wei-Cheng; Huang, Shih-Ting; Hung, Yao-Min; Yang, Chen-Chang

    2016-05-01

    A total of 112 cases of Naja atra envenomation were examined at two referring hospitals: Taichung Veterans General Hospital in central Taiwan and Taipei Veterans General Hospital (VGH-TP) in northern Taiwan. Overall, 77% (86/112) of cases developed clinically suspected wound infections and 54% (61/112) required surgery secondary to tissue necrosis, finger or toe gangrene, and/or necrotizing fasciitis. Morganella morganii was the most abundant gram-negative bacterial strain isolated from bite wounds, followed by Proteus spp., Aeromonas hydrophila, Pseudomonas aeruginosa, and Providencia spp. in descending order; Enterococcus spp. were the most common gram-positive bacteria and Bacteroides spp. were the only anaerobic bacteria. A few episodes of bacteremia were caused by Bacteroides and Shewanella spp. There were no significant variations in the distribution of bacterial species between these two hospitals except for a higher incidence of M. morganii, Enterococcus spp., and polymicrobial infection observed at VGH-TP, which may have been related to variations in the fecal flora of prey and oral flora of individual snakes in different geographic areas in Taiwan. According to the susceptibility test involving various pathogens, first-line drug options for the management of N. atra snakebite wound infections may include monotherapy with ureidopenicillin or combination therapy with aminopenicillin and a third-generation cephalosporin or fluoroquinolone. A prospective evaluation of empiric antibiotic therapy for the management of N. atra snakebite should be considered. PMID:26976881

  19. 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

  20. Assessment of Treatment of Community Acquired Severe Pneumonia by Two Different Antibiotics

    PubMed Central

    Bilal, Jalal Ali; Eldouch, Widad; Abdin, Ali

    2016-01-01

    Introduction Pneumonia is common presentation in the emergency room and is still a cause of morbidity and mortality. The rationale of this study was to test the trend of paediatricians to achieve rapid response facing severe pneumonia, the lack of agreed on plan for the management of community acquired pneumonia (CAP) and the few experiences regarding injectable form of β-lactam antimicrobial. Materials and Methods This is a prospective case control study, purposive randomized sampling, three patients were excluded since their information was incomplete, 132 patients were randomly divided into groups, one group named control group (penicillin according to the guidelines of WHO 2013), 33 patients; second group treated by β-lactam inhibitors (Augmentin IV) 50 patients; and third group treated by 3rd generation cephalosporin (ceftriaxone) 49 patients. The study was conducted at the main tertiary care and paediatrics teaching hospital in Khartoum capital of Sudan. The study was completed within the duration from 2010 to 2011. Results Both group showed more or less similar results regarding response, as well as the failure rate however, the Augmentin and ceftriaxone groups showed a little bit better survival than the control group. Conclusion Antibiotics decrease the mortality rate among the pneumonia patients provided that it is given early in the disease. PMID:27437318

  1. Antibiotic usage in 2013 on a dairy CAFO in NY State, USA.

    PubMed

    Doane, Marie; Sarenbo, Sirkku

    2014-01-01

    Antimicrobial resistance is threatening humans and animals worldwide. Biosecurity and 1-year usage of antibiotics on a dairy concentrated animal feeding operation (CAFO) in NY State, USA, were mapped: how much antibiotics were used, for what purpose, and whether any decrease could be warranted. Approximately 493 kg antibiotics was used, of which 376 kg was ionophores (monensin and lasalocides), 79 kg penicillin, 16.5 kg lincosamides, 8.0 kg aminoglycosides, 7.7 kg sulfamides, 3.4 kg cephalosporin, 2 kg macrolides, 0.7 kg amphenicols, and 0.1 kg fluoroquinolones. Usage reduction by 84% was realistic without compromising the animal welfare. Further reduction could be possible by improving the biosecurity and by utilizing antibiotic sensitivity testing. PMID:24891936

  2. 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, 28°C and 35°C, following Clinical and Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, β-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

  3. Antibiotic usage in 2013 on a dairy CAFO in NY State, USA

    PubMed Central

    Doane, Marie; Sarenbo, Sirkku

    2014-01-01

    Antimicrobial resistance is threatening humans and animals worldwide. Biosecurity and 1-year usage of antibiotics on a dairy concentrated animal feeding operation (CAFO) in NY State, USA, were mapped: how much antibiotics were used, for what purpose, and whether any decrease could be warranted. Approximately 493 kg antibiotics was used, of which 376 kg was ionophores (monensin and lasalocides), 79 kg penicillin, 16.5 kg lincosamides, 8.0 kg aminoglycosides, 7.7 kg sulfamides, 3.4 kg cephalosporin, 2 kg macrolides, 0.7 kg amphenicols, and 0.1 kg fluoroquinolones. Usage reduction by 84% was realistic without compromising the animal welfare. Further reduction could be possible by improving the biosecurity and by utilizing antibiotic sensitivity testing. PMID:24891936

  4. Surveillance of antibiotic resistance

    PubMed Central

    Johnson, Alan P.

    2015-01-01

    Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

  5. Sample preservation for the analysis of antibiotics in water.

    PubMed

    Llorca, Marta; Gros, Meritxell; Rodríguez-Mozaz, Sara; Barceló, Damià

    2014-11-21

    This paper describes a stability study performed for 56 antibiotics belonging to 9 different groups--macrolides, tetracyclines, fluoroquinolones, quinolones, penicillins, cephalosporines, lincosamides, sulfonamides and nitroimidazole antibiotics--in purified water samples fortified with the selected compounds at 10 ng/ml. For this purpose, three different sample preservation modes were tested with the aim of avoiding biotic and abiotic degradation: (i) storage at -20°C, (ii) storage at -20°C with 0.1% of EDTA and (iii) pre-concentration in a solid phase extraction cartridge (SPE), which was afterwards stored at -20°C. Concentrations of antibiotics in the samples preserved using the different protocols were monitored after 0, 1, 2 and 12 weeks. The results showed that, for the accurate determination of all compounds they should be analyzed right after sampling. However, if this is not possible, most of the antibiotics can be analyzed within the 1st week after sampling and preservation at -20°C (with or without EDTA) or in a SPE cartridges at -20°C. Nonetheless, some antibiotics found extensively in the environment, such as sulfamethoxazole, ciprofloxacin, ofloxacin, erythromycin, azithromycin and clarithromycin exhibited low stability after 1 week preservation and, therefore, they should be analyzed within this time. PMID:25441070

  6. 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.

  7. 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

  8. Ciprofloxacin residue and antibiotic-resistant biofilm bacteria in hospital effluent.

    PubMed

    Ory, Jérôme; Bricheux, Geneviève; Togola, Anne; Bonnet, Jean Louis; Donnadieu-Bernard, Florence; Nakusi, Laurence; Forestier, Christiane; Traore, Ousmane

    2016-07-01

    Discharge of antimicrobial residues and resistant bacteria in hospital effluents is supposed to have strong impacts on the spread of antibiotic resistant bacteria in the environment. This study aimed to characterize the effluents of the Gabriel Montpied teaching hospital, Clermont-Ferrand, France, by simultaneously measuring the concentration of ciprofloxacin and of biological indicators resistant to this molecule in biofilms formed in the hospital effluent and by comparing these data to ciprofloxacin consumption and resistant bacterial isolates of the hospital. Determination of the measured environmental concentration of ciprofloxacin by spot sampling and polar organic chemical integrative (POCIS) sampling over 2 weeks, and comparison with predicted environmental concentrations produced a hazard quotient >1, indicating a potential ecotoxicological risk. A negative impact was also observed with whole hospital effluent samples using the Tetrahymena pyriformis biological model. During the same period, biofilms were formed within the hospital effluent, and analysis of ciprofloxacin-resistant isolates indicated that Gamma-Proteobacteria were numerous, predominantly Aeromonadaceae (69.56%) and Enterobacteriaceae (22.61%). Among the 115 isolates collected, plasmid-mediated fluoroquinolone-resistant genes were detected, with mostly aac(6')-lb-cr and qnrS. In addition, 60% of the isolates were resistant to up to six antibiotics, including molecules mostly used in the hospital (aminosides and third-generation cephalosporins). In parallel, 1247 bacteria isolated from hospitalized patients and resistant to at least one of the fluoroquinolones were collected. Only 5 of the 14 species identified in the effluent biofilm were also found in the clinical isolates, but PFGE typing of the Gram-negative isolates found in both compartments showed there was no clonality among the strains. Altogether, these data confirm the role of hospital loads as sources of pollution for wastewater

  9. Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

    PubMed Central

    Barry, B; Muffat-Joly, M; Bauchet, J; Faurisson, F; Gehanno, P; Pocidalo, J J; Carbon, C

    1996-01-01

    We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media. PMID:8878566

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

    PubMed

    Angel Villegas, Natalia; Baronetti, José; Albesa, Inés; Etcheverría, Analía; 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

  11. Pemphigus vulgaris after coxsackievirus infection and cephalosporin treatment: a paraviral eruption?

    PubMed

    Ruocco, E; Lo Schiavo, A; Baroni, A; Sangiuliano, S; Puca, R V; Brunetti, G; Ruocco, V

    2008-01-01

    Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous agents, mainly drugs and viruses. Herein we report the case of a 66-year-old woman referred to our department for the onset of painful oral erosions and bullous lesions on the torso. Clinical, laboratory and histopathological investigations led to the diagnosis of pemphigus vulgaris. Two weeks before the outbreak of the lesions, the patient had suffered from a viral pharyngitis, subsequently diagnosed as herpangina, and had been taking an oral cephalosporin (cefixime) for 1 week to prevent possible bacterial complications. A relationship between the onset of pemphigus and coxsackievirus infection or cefixime administration or both was supposed. The case may represent a peculiar paraviral eruption, where a predisposing pemphigus-prone genetic background paved the way for the acantholytic autoimmune disorder as a consequence of the combined effect of the coxsackievirus infection and the cephalosporin treatment. PMID:18230979

  12. Horizontal Transfer of Plasmid-Mediated Cephalosporin Resistance Genes in the Intestine of Houseflies (Musca domestica).

    PubMed

    Fukuda, Akira; Usui, Masaru; Okubo, Torahiko; Tamura, Yutaka

    2016-06-01

    Houseflies are a mechanical vector for various types of bacteria, including antimicrobial-resistant bacteria (ARB). If the intestine of houseflies is a suitable site for the transfer of antimicrobial resistance genes (ARGs), houseflies could also serve as a biological vector for ARB. To clarify whether cephalosporin resistance genes are transferred efficiently in the housefly intestine, we compared with conjugation experiments in vivo (in the intestine) and in vitro by using Escherichia coli with eight combinations of four donor and two recipient strains harboring plasmid-mediated cephalosporin resistance genes and chromosomal-encoded rifampicin resistance genes, respectively. In the in vivo conjugation experiment, houseflies ingested donor strains for 6 hr and then recipient strains for 3 hr, and 24 hr later, the houseflies were surface sterilized and analyzed. In vitro conjugation experiments were conducted using the broth-mating method. In 3/8 combinations, the in vitro transfer frequency (Transconjugants/Donor) was ≥1.3 × 10(-4); the in vivo transfer rates of cephalosporin resistance genes ranged from 2.0 × 10(-4) to 5.7 × 10(-5). Moreover, cephalosporin resistance genes were transferred to other species of enteric bacteria of houseflies such as Achromobacter sp. and Pseudomonas fluorescens. These results suggest that houseflies are not only a mechanical vector for ARB but also a biological vector for the occurrence of new ARB through the horizontal transfer of ARGs in their intestine. PMID:26683492

  13. Metabolic engineering of β-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis.

    PubMed

    Veiga, Tânia; Gombert, Andreas K; Landes, Nils; Verhoeven, Maarten D; Kiel, Jan A K W; Krikken, Arjen M; Nijland, Jeroen G; Touw, Hesselien; Luttik, Marijke A H; van der Toorn, John C; Driessen, Arnold J M; Bovenberg, Roel A L; van den Berg, Marco A; van der Klei, Ida J; Pronk, Jack T; Daran, Jean-Marc

    2012-07-01

    Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via β-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of β-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of β-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis. PMID:22525490

  14. Clostridium difficile infection following systemic antibiotic administration in randomised controlled trials: a systematic review and meta-analysis.

    PubMed

    Vardakas, Konstantinos Z; Trigkidis, Kyriakos K; Boukouvala, Eleni; Falagas, Matthew E

    2016-07-01

    Antibiotics have been the most important risk factor for Clostridium difficile infection (CDI). However, only data from non-randomised studies have been reviewed. We sought to evaluate the risk for development of CDI associated with the major antibiotic classes by analysing data from randomised controlled trials (RCTs). The PubMed, Cochrane and Scopus databases were searched and the references of selected RCTs were also hand-searched. Eligible studies should have compared only one antibiotic versus another administered systemically. Inclusion of studies comparing combinations of antibiotics was allowed only if the second antibiotic was the same or from the same class or if it was administered in a subset of the enrolled patients who were equally distributed in the two arms. Only a minority of the selected RCTs (79/1332; 5.9%) reported CDI episodes. Carbapenems were associated with more CDI episodes than fluoroquinolones [risk ratio (RR) = 2.44, 95% confidence interval (CI) 1.32-4.49] and cephalosporins (RR = 2.24, 95% CI 1.46-3.42), but not penicillins (RR = 2.53, 95% CI 0.87-7.41). Cephalosporins were associated with more CDIs than penicillins (RR = 2.36, 95% CI 1.32-4.23) and fluoroquinolones (RR = 2.84, 95% CI 1.60-5.06). There was no difference in CDI frequency between fluoroquinolones and penicillins (RR = 1.34, 95% CI 0.55-3.25). Finally, clindamycin was associated with more CDI episodes than cephalosporins and penicillins (RR = 3.92, 95% CI 1.15-13.43). In conclusion, data from RCTs showed that clindamycin and carbapenems were associated with more CDIs than other antibiotics. PMID:27216385

  15. The structural basis of cephalosporin formation in a mononuclear ferrous enzyme.

    PubMed

    Valegård, Karin; Terwisscha van Scheltinga, Anke C; Dubus, Alain; Ranghino, Graziella; Oster, Linda M; Hajdu, Janos; Andersson, Inger

    2004-01-01

    Deacetoxycephalosporin-C synthase (DAOCS) is a mononuclear ferrous enzyme that transforms penicillins into cephalosporins by inserting a carbon atom into the penicillin nucleus. In the first half-reaction, dioxygen and 2-oxoglutarate produce a reactive iron-oxygen species, succinate and CO2. The oxidizing iron species subsequently reacts with penicillin to give cephalosporin and water. Here we describe high-resolution structures for ferrous DAOCS in complex with penicillins, the cephalosporin product, the cosubstrate and the coproduct. Steady-state kinetic data, quantum-chemical calculations and the new structures indicate a reaction sequence in which a 'booby-trapped' oxidizing species is formed. This species is stabilized by the negative charge of succinate on the iron. The binding sites of succinate and penicillin overlap, and when penicillin replaces succinate, it removes the stabilizing charge, eliciting oxidative attack on itself. Requisite groups of penicillin are within 1 A of the expected position of a ferryl oxygen in the enzyme-penicillin complex. PMID:14718929

  16. 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 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.

  17. [Side effects and consequences of frequently used antibiotics in clinical practice].

    PubMed

    Cerny, A

    1996-03-30

    Oral antimicrobial substances belonging to the beta-lactams, quinolones, macrolides, tetracyclines and the trimethoprim-sulfamethoxazole combination are among the most prescribed classes of drugs in private practice. Knowledge of the potential side effects considered in the light of various patient-associated factors such as genetic makeup, renal and liver function, underlying diseases, drug allergies and coadministered drugs, is important in order to minimize the risk of adverse reactions. This article reviews important side effect patterns and focuses on more recent aspects of antibiotic-associated diarrhea and beta-lactam allergy relevant to the practicing physician. Diarrhea occurring during antibiotic treatment raises the possibility of Clostridium-difficile-associated disease, which may evolve into life-threatening toxic megacolon. Mild cases with resolving symptoms after discontinuation of the antibiotic usually do not require further workup. More severe cases with watery diarrhea, abdominal pain, dehydration and electrolyte abnormalities warrant rapid diagnosis, cessation of antibiotic treatment and specific treatment including oral metronidazole. The use of oral vancomycin as a first line drug is discouraged because of the possibility of selecting vancomycin-resistant enterococci. Hypersensitivity reactions to beta-lactams are the most important type of side effects which can often be prevented. Patients with a history of beta-lactam associated IgE-mediated hypersensitivity (hives, wheezing or hypotension) should undergo penicillin skin testing. The frequently observed maculopapular rash associated with aminopenicillins without hives is in most cases not caused by an IgE-mediated mechanism. Patients with previous life-threatening penicillin allergy such as anaphylaxis or Lyell's syndrome should not undergo skin testing. Currently available tests do not reliably predict cephalosporin hypersensitivity. More recent data suggest that crossreactivity between

  18. Bacteria subsisting on antibiotics.

    PubMed

    Dantas, Gautam; Sommer, Morten O A; Oluwasegun, Rantimi D; Church, George M

    2008-04-01

    Antibiotics are a crucial line of defense against bacterial infections. Nevertheless, several antibiotics are natural products of microorganisms that have as yet poorly appreciated ecological roles in the wider environment. We isolated hundreds of soil bacteria with the capacity to grow on antibiotics as a sole carbon source. Of 18 antibiotics tested, representing eight major classes of natural and synthetic origin, 13 to 17 supported the growth of clonal bacteria from each of 11 diverse soils. Bacteria subsisting on antibiotics are surprisingly phylogenetically diverse, and many are closely related to human pathogens. Furthermore, each antibiotic-consuming isolate was resistant to multiple antibiotics at clinically relevant concentrations. This phenomenon suggests that this unappreciated reservoir of antibiotic-resistance determinants can contribute to the increasing levels of multiple antibiotic resistance in pathogenic bacteria. PMID:18388292

  19. Molecular-weight-dependent, anionic-substrate-preferential transport of β-lactam antibiotics via multidrug resistance-associated protein 4.

    PubMed

    Akanuma, Shin-Ichi; Uchida, Yasuo; Ohtsuki, Sumio; Kamiie, Jun-ichi; Tachikawa, Masanori; Terasaki, Tetsuya; Hosoya, Ken-ichi

    2011-01-01

    β-Lactam antibiotics have cerebral and peripheral adverse effects. Multidrug resistance-associated protein 4 (MRP4) has been reported to transport several β-lactam antibiotics, and its expression at the blood-brain barrier also serves to limit their distribution to the brain. Therefore, the purpose of this study was to clarify the structure-activity relationship of MRP4-mediated transport of β-lactam antibiotics using MRP4-expressing Sf9 membrane vesicles. The transport activity was evaluated as MRP4-mediated transport per MRP4 protein [nL/(min·fmol MRP4 protein)] based on measurement of MRP4 protein expression by means of liquid chromatography-tandem mass spectrometry. Cefotiam showed the greatest MRP4-mediated transport activity [8.90 nL/(min·fmol MRP4 protein)] among the β-lactam antibiotics examined in this study. Measurements of differential transport activity of MRP4 for various β-lactam antibiotics indicated that (i) cephalosporins were transported via MRP4 at a greater rate than were penams, β-lactamase inhibitors, penems, or monobactams; (ii) MRP4-mediated transport activity of anionic cephalosporins was greater than that of zwitterionic cephalosporins; and (iii) higher-molecular-weight anionic β-lactam antibiotics showed greater MRP4-mediated transport activity than lower-molecular-weight ones, whereas zwitterionic β-lactam antibiotics did not show molecular weight dependency of MRP4-mediated transport. These quantitative data should prove useful for understanding MRP-related adverse effects of β-lactam antibiotics and their derivatives. PMID:21897051

  20. Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia.

    PubMed

    Sánchez, María B

    2015-01-01

    Stenotrophomonas maltophilia is an environmental bacterium found in the soil, associated with plants and animals, and in aquatic environments. It is also an opportunistic pathogen now causing an increasing number of nosocomial infections. The treatment of S. maltophilia is quite difficult given its intrinsic resistance to a number of antibiotics, and because it is able to acquire new resistances via horizontal gene transfer and mutations. Certainly, strains resistant to quinolones, cotrimoxale and/or cephalosporins-antibiotics commonly used to treat S. maltophilia infections-have emerged. The increasing number of available S. maltophilia genomes has allowed the identification and annotation of a large number of antimicrobial resistance genes. Most encode inactivating enzymes and efflux pumps, but information on their role in intrinsic and acquired resistance is limited. Non-typical antibiotic resistance mechanisms that also form part of the intrinsic resistome have been identified via mutant library screening. These include non-typical antibiotic resistance genes, such as bacterial metabolism genes, and non-inheritable resistant phenotypes, such as biofilm formation and persistence. Their relationships with resistance are complex and require further study. PMID:26175724

  1. Antibiotic consumption in non-teaching Lebanese hospitals: A cross-sectional study.

    PubMed

    Iskandar, Katia; Hanna, Pierre A; Salameh, Pascale; Raad, Etwal B

    2016-01-01

    The rising threat of antibiotic resistance is linked to patterns of antibiotic use in hospital settings where global efforts are undertaken to encourage reporting and benchmarking antibiotic consumption in an attempt to improve prescription regimens. In Lebanon, where data concerning the level of antibiotic consumption in hospitals is scarce, the aim of our paper is to track the intensity of antibiotic consumption in order to identify potential evidence of antibiotic misuse or abuse. The study is conducted in 2012 for a period of 12-month using data from pharmacy records in 27 non-teaching Lebanese hospitals according to the Anatomical, Therapeutic and chemical classification system and Defined Daily Dose (ATC/DDD) recommended by the World Health Organization and compiling data on ABC Calc software version 3.1. Results show that the average antibiotic consumption excluding pediatric cases is 72.56 Defined Daily Dose per 100 Bed-Days (DDD/100BD). Total broad spectrum antibiotic consumption is 12.14 DDD/100BD with no significant difference found between public and private hospitals (p>0.05 for all). The most commonly used antibiotics were Amoxycillin/Clavulanic acid, Ceftriaxone, Amoxycillin and Cefuroxime for parenteral use. Consumption of beta-lactams, Cephalosporins, Carbapenems, Monobactams and quinolones did not vary significantly by region, occupancy rate, number of beds including the number of intensive care unit beds. Our data findings provides baseline information on patterns of antibiotic consumption in Lebanon and the issue calls for concerted efforts to encourage data reporting on national basis and to correlate future findings with results of antibiotic susceptibility testing which can provide insights and tools needed to assess the public health consequences of antimicrobial misuse and to evaluate the impact of antibiotic resistance containment interventions. PMID:26806876

  2. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic.

    PubMed

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents - linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2, 5

  3. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic

    PubMed Central

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents — linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2

  4. Combating Antibiotic Resistance

    MedlinePlus

    ... for infectious diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...

  5. Antibiotics and Resistance: Glossary

    MedlinePlus

    ... induced by natural or human activity on the ecology and living organisms. Ecology The study of the relationships and interactions between ... antibiotics The Cost of Resistance Science of Resistance Ecology Antibiotics in Agriculture Antibacterial Agents Glossary References Web ...

  6. MedlinePlus: Antibiotics

    MedlinePlus

    ... or not using them properly, can add to antibiotic resistance . This happens when bacteria change and become able ... ports Pseudomembranous colitis Sensitivity analysis Related Health Topics Antibiotic Resistance Bacterial Infections Medicines National Institutes of Health The ...

  7. Efficacy evaluation of some antibiotics against syrian brucella spp isolates, in vitro

    PubMed Central

    Safi, Mazen; Al-Mariri, Ayman

    2012-01-01

    Brucellosis is an endemic zoonosis in Syria, affecting large numbers of animals and there are an increasing number of cases in humans. The aim of this study is to investigate the in vitro efficacy of various traditional and new antibiotics against 89 Brucella isolates (isolated from domestic animals) collected from different Syrian regions. Minimum inhibitory concentrations (MICs) of seventeen antibiotics were determined. Ciprofloxacin and ofloxacin were the most effective antibiotics, whereas sparfloxacin, levofloxacin, doxycycline and tetracycline had a moderate activity. In contrast, moxifloxacin and rifampicin had a low activity, while streptomycin, spiramycin and cephalosporines were ineffective. As a result, we come to the conclusion that a combination between one effective quinolone and doxycycline has a good efficacy against Brucella. Further in vivo studies are necessary to support this suggestion. PMID:24031952

  8. 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.

  9. Antibiotic susceptibility profile of Aeromonas spp. isolates from food in Abu Dhabi, United Arab Emirates.

    PubMed

    Awan, Mohammad Bashir; Maqbool, Ahmed; Bari, Abdul; Krovacek, Karel

    2009-01-01

    A total of 57 Aeromonas isolates from food samples such as fresh and frozen chicken, game birds, pasteurized milk, baby food, bakery products, fruit and vegetables, fish, and water from Abu Dahbi, UAE were investigated for antibiotic susceptibility profile. Most strains were resistant to penicillins (ticarcillin, mezlocillin, oxacillin, piperacillin), sulfamethoxazole, trimethoprim and macrolides (erythromycin, vancomycin, clindamycin) but sensitive to tetracycline, chloramphenicol, nitrofurantoin, aminoglycosides (amikacin, gentamicin, tobramycin), cephalosporins (cefuroxime, ceftrioxone, cefazolin, cephalexin, cephalothin, cefoxitin, cefotaxime), quinolone (ciprofloxacin), colistin sulphate and SXT (trimethoprim-sulfamethoxazole). On the other hand, many antibiotics showed excellent inhibitory activity (>75% strains were sensitive to them) against all the strains tested. These include cefuroxime, ceftrioxone, ciprofloxacin, colistin, amikacin, gentamicin, tetracycline, chloramphenicol, nitrofurantoin, cefotaxime and tobramycin. In conclusion, the results show a detailed pattern of sensitivity of the various Aeromonas spp. isolates to a variety of antibiotics and provide useful information in the context of selective isolation and phenotypic identification of the aeromonads from food. PMID:19382665

  10. Occupational Asthma in Antibiotic Manufacturing Workers: Case Reports and Systematic Review

    PubMed Central

    Díaz Angulo, Sara; Szram, Joanna; Welch, Jenny; Cannon, Julie; Cullinan, Paul

    2011-01-01

    Background. The risks of occupational asthma (OA) from antibiotics are uncertain. We report 4 new cases and a systematic review of the literature. Methods. Cases were identified through a specialist clinic, each underwent specific provocation testing (SPT). We subsequently reviewed the published literature. Results. The patients were employed in the manufacture of antibiotics; penicillins were implicated in three cases, in the fourth erythromycin, not previously reported to cause OA. In two, there was evidence of specific IgE sensitisation. At SPT each developed a late asthmatic reaction and increased bronchial hyperresponsiveness. 36 case reports have been previously published, 26 (citing penicillins or cephalosporins). Seven cross-sectional workplace-based surveys found prevalences of 5–8%. Conclusions. OA in antibiotic manufacturers may be more common than is generally recognised. Its pathogenesis remains unclear; immunological tests are of uncertain value and potential cases require confirmation with SPT. Further study of its frequency, mechanisms, and diagnosis is required. PMID:21603168