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Showing papers on "Penicillin published in 2012"


Journal ArticleDOI
TL;DR: Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs and that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedication swine.
Abstract: Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.

824 citations


Journal ArticleDOI
TL;DR: The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing.
Abstract: The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

492 citations


Journal ArticleDOI
TL;DR: Overall cross reactivity between penicillins and cephalosporins is lower than previously reported, though there is a strong association between amoxicillin and ampicillin with first- and second-generation cep Halosporin that share a similar R1 side chain.
Abstract: Background The practice of avoiding cephalosporin administration to penicillin-allergic patients persists despite the low rate of cross reactions between both groups of antibiotics. Objective The purpose of this literature review is to evaluate the published evidence regarding the commonly held belief that patients with a history of an allergic reaction to penicillin have a significantly increased risk of an allergic reaction to cephalosporins. Materials and Methods Articles were identified through a computerized search of MEDLINE from 1950 to the present using the search terms “penicillin$,” “cephalosporin$,” “allerg$,” “hypersensitivity,” and “cross-react$.” All articles were reviewed, and additional sources cited in them were added to the literature review. Results Penicillins have a cross allergy with first-generation cephalosporins (odds ratio 4.8; confidence interval 3.7–6.2) and a negligible cross allergy with second-generation cephalosporins (odds ratio 1.1; confidence interval 0.6–2.1). Laboratory and cohort studies confirm that the R1 side chain is responsible for this cross reactivity. Overall cross reactivity between penicillins and cephalosporins is lower than previously reported, though there is a strong association between amoxicillin and ampicillin with first- and second-generation cephalosporins that share a similar R1 side chain. Conclusions Although a myth persists that approximately 10% of patients with a history of penicillin allergy will have an allergic reaction if given a cephalosporin, the overall cross-reactivity rate is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains. However, a single study reported the prevalence of cross reactivity with cefadroxil as high as 27%. For penicillin-allergic patients, the use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy.

166 citations


Journal ArticleDOI
TL;DR: The mechanisms of action of the antibiotics most commonly used in the periodontal treatment, penicillin, tetracycline, macrolide and metronidazole and the main mechanisms of bacterial resistance to these drugs are reviewed.
Abstract: Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections.

161 citations


Journal ArticleDOI
TL;DR: A change to the simpler azithromycin treatment regimen could enable yaws elimination through mass drug administration programmes and avoids the need for injection equipment and medically trained personnel.

134 citations


Journal ArticleDOI
TL;DR: Nares of healthy sheep could be a reservoir of PVL-positive community-associated-MRSA and also of TSST-positive S. aureus isolates, with potential implications in public health.

81 citations


Journal ArticleDOI
TL;DR: Herd-level use of certain antimicrobials administered for mastitis treatment and control, such as intramammary penicillin and pirlimycin as well as systemically administered penichill and florfenicol, was positively associated with antimicrobial resistance in bovine mastitis pathogens in the field conditions.

79 citations


Journal ArticleDOI
TL;DR: Helicobacter pylori eradication rates with standard triple therapy are declining worldwide, and new treatment combinations for antibiotic resistant H.pylori strains are required, especially for patients with penicillin allergy.
Abstract: SummaryBackground Helicobacter pylori eradication rates with standard triple therapy are declining worldwide. The optimal management of H. pylori is evolving and new treatment combinations for antibiotic resistant H. pylori strains are required, especially for patients with penicillin allergy. Aim To review the effectiveness of alternative antibiotic combinations and necessity of pre-antibiotic sensitivity testing. Methods A total of 310 consecutive patients who had failed at least one course of standard 7-day triple therapy initially prescribed by their physicians were included in this study between year 2007 and 2011. Antibiotics were prescribed based on pre-antibiotic sensitivity tests and, if any, patient's allergy to penicillin. Results In 98.7% of the patients' samples, H. pylori was successfully cultured. The proportion resistant to clarithromycin and metronidazole was 94.1% and 67.6% respectively, with 65% resistant to both. For the in-house primary quadruple therapy, with Proton pump inhibitor, Amoxicillin, Rifabutin and Ciprofloxacin (PARC), H. pylori was successfully eradicated in 95.2% of patients. For patients allergic to amoxicillin, an alternative quadruple therapy using Proton pump inhibitor, Bismuth subcitrate, Rifabutin and Ciprofloxacin (PBRC) gave an eradication rate of 94.2%. Patients needing alternative salvage therapy were given novel personalised combinations consisting of bismuth, rifabutin, tetracycline or furazolidone; the eradication rate was 73.8%. Conclusions Patients who present with antibiotic resistant H. pylori can be confidently treated with PARC, PBRC or other personalised salvage therapies. These regimens can be used when treatment options are limited by penicillin allergy. Pre-treatment H. pylori antibiotic sensitivity tests contributed to the high eradication rate in this study.

74 citations


Journal ArticleDOI
TL;DR: BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.
Abstract: Background BC-3781 is an investigational semi-synthetic pleuromutilin antibiotic, which recently finished a clinical Phase 2 trial in acute bacterial skin and skin structure infections. BC-3781 binds to the 50S ribosomal subunit and cross-resistance with other antimicrobial classes is uncommon. We evaluated the activity of BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs). Methods BC-3781 and comparator agents were susceptibility tested against Streptococcus pneumoniae (157 isolates; 33% penicillin resistant), Haemophilus influenzae (102; 50% β-lactamase producers), Moraxella catarrhalis (50) and Legionella pneumophila (30) by broth microdilution and the agar dilution method. Mycoplasma pneumoniae (50 strains) was tested by broth microdilution, while Chlamydophila pneumoniae (50 strains) MIC values were determined using HEp-2 cells. Results Against S. pneumoniae (MIC(50/90) 0.12/0.25 mg/L) BC-3781 was 16- and 8-fold more active than azithromycin (MIC(50/90) 2/>16 mg/L) and levofloxacin (MIC(50/90) 1/1 mg/L), respectively, and its activity was not adversely affected by resistance to penicillin. S. pneumoniae showed high resistance rates to azithromycin (50.3%) and clindamycin (31.2%), all being inhibited by BC-3781 at concentrations ≤0.5 mg/L. H. influenzae and M. catarrhalis exhibited low BC-3781 MIC values independent of β-lactamase production. BC-3781 activity against L. pneumophila (MIC(50/90) 0.06/0.5 mg/L) was similar to that of erythromycin, but lower than that of azithromycin. BC-3781 also showed potent activity against M. pneumoniae and C. pneumoniae, with MIC(50/90) of 0.006/0.006 and 0.02/0.04 mg/L, respectively. Conclusions BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.

74 citations



Journal ArticleDOI
TL;DR: Combination of antibiotics with antimicrobial peptides could allow reduced use of antibiotics in medical applications and could help slow the emergence of bacteria resistant to antibiotics.

Journal Article
TL;DR: The developed method was fully validated in terms of selectivity, linearity, accuracy, precision, stability and sensitivity according to the European Union Decision 2002/657/EC.
Abstract: A confirmatory high performance liquid chromatography method for the determination of six penicillin antibiotics and three amphenicol antibiotics in gilthead seabream (Sparus Aurata) tissue was developed. Ampicillin (AMP), penicillin G (PG), penicillin V (PV), oxacillin (OXA), cloxacillin (CLO), dicloxacillin (DICLO), thiamphenicol (TAP), florfenicol (FFC) and chloramphenicol (CAP) were separated on an Inertsil, C8 (250 × 4 mm, 5 µm) column by gradient elution with a mobile phase consisting of ammonium acetate 0.05 M and acetonitrile at 25 °C. Diode array detection with monitoring at 225 nm (for the determination of AMP, PG, PV, TAP and FFC), 240 nm (for OXA, CLO and DICLO) and 278 nm (for CAP) was applied. Examined antibiotics were isolated from gilthead seabream tissue by liquid-liquid extraction and further clean-up was performed by solid phase extraction using Oasis HLB (200 mg/6 mL) cartridges. The developed method was fully validated in terms of selectivity, linearity, accuracy, precision, stability and sensitivity according to the European Union Decision 2002/657/EC.

Journal ArticleDOI
TL;DR: It was showed that CoNS and E. coli are the most common causative agents of nosocomial BSIs and UTIs, and control of infection needs to be addressed in both antibiotic prescription and general hygiene.
Abstract: Treatment of nosocomial infections is becoming difficult due to the increasing trend of antibiotics resistance. Current knowledge on antibiotic resistance pattern is essential for appropriate therapy. We aimed to evaluate antibiotic resistance profiles in nosocomial bloodstream and urinary tract pathogens. A total of 129 blood stream and 300 urinary tract positive samples were obtained from patients referring to Besat hospital over a two-year period (2009 and 2010). Antibiotic sensitivity was ascertained using the Kirby-Bauer disk diffusion technique according to CLSI guidelines. Patient's data such as gender and age were recorded. The ratio of gram-negative to gram-positive bacteria in BSIs was 1.6 : 1. The most prevalent BSI pathogen was Coagulase-Negative Staphylococci (CoNS). The highest resistance rate of CoNS was against penicillin (91.1%) followed by ampicillin (75.6%), and the lowest rate was against vancomycin (4.4%). Escherichia coli was the most prevalent pathogen isolated from urinary tract infections (UTIs). Ratio of gram-negative to gram-positive bacteria was 3.2 : 1. The highest resistance rate of E. coli isolates was against nalidixic acid (57.7%). The present study showed that CoNS and E. coli are the most common causative agents of nosocomial BSIs and UTIs, and control of infection needs to be addressed in both antibiotic prescription and general hygiene.

Journal ArticleDOI
N. Zhou1, Jing Zhang1, Mingtao Fan1, Jianlong Wang1, G. Guo, Wei Xiaoshi1 
TL;DR: Evaluating the susceptibility of 43 strains of lactic acid bacteria isolated from Chinese yogurts made in different geographical areas to 11 antibiotics found widespread resistance to ampicillin, chloramphenicol, chlortetracy Cline, tetracyclines, lincomycin, streptomycin, neomycin; and gentamycin was found among the 35 strains tested.

Journal ArticleDOI
TL;DR: The molecular diversity, antibiotic resistance patterns and presence of resistance genes were determined in Staphylococcus aureus isolates from cases of bovine mastitis in a dairy cattle herd in China.
Abstract: The molecular diversity, antibiotic resistance patterns and presence of resistance genes were determined in Staphylococcus aureus isolates from cases of bovine mastitis in a dairy cattle herd in China. Multiple locus variable number tandem repeat analysis was used for molecular typing. Resistance was determined through minimum inhibitory concentrations and resistance genes were detected by PCR. There was low molecular diversity; one predominant strain (type I) accounted for the majority of cases of S. aureus mastitis in the herd and this strain had a high frequency of resistance to penicillin and tetracycline. The most prevalent resistance genes were blaZ, ermC and tetM.

Journal ArticleDOI
TL;DR: It is shown that penicillin production in high-yielding strains can be further improved by the overexpression of IAT while at very high levels of I AT the precursor 6-aminopenicillic acid (6-APA) accumulates.
Abstract: cIntense classical strain improvement has yielded industrial Penicillium chrysogenum strains that produce high titers of penicillin. These strains contain multiple copies of the penicillin biosynthesis cluster encoding the three key enzymes: d-(l-a-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), isopenicillin N synthase (IPNS), and isopenicillin N acyltransferase (IAT). The phenylacetic acid coenzyme A (CoA) ligase (PCL) gene encoding the enzyme responsible for the activation of the side chain precursor phenylacetic acid is localized elsewhere in the genome in a single copy. Since the protein level of IAT already saturates at low cluster copy numbers, IAT might catalyze a limiting step in high-yielding strains. Here, we show that penicillin production in high-yielding strains can be further improved by the overexpression of IAT while at very high levels of IAT the precursor 6-aminopenicillic acid (6-APA) accumulates. Overproduction of PCL only marginally stimulates penicillin production. These data demonstrate that in high-yielding strains IAT is the limiting factor and that this limitation can be alleviated by a balanced overproduction of this enzyme.

Journal ArticleDOI
TL;DR: The findings underscore the need to monitor blood culture isolates and their antimicrobial resistance patterns to observe resistance trends that would influence appropriate empiric treatment and infection control strategies for bacteremic children.
Abstract: Introduction: Bloodstream infections (BSI) are a serious cause of morbidity and mortality worldwide. Emerging antimicrobial drug resistance among bacterial pathogens causing BSI can limit therapeutic options and complicate patient management. Methodology: To encourage the prudent use of appropriate antibiotics in our pediatric population at Children's Medical Center Hospital, Tehran, Iran, we studied the frequency and antibiogram patterns of blood culture isolates from January 2001 to December 2005. Results: Of 25,223 blood cultures examined, 2,581 (10.23 %) were positive for bacterial growth. The frequency of Gram-positive bacteria isolated was 47.6% (1228 of 2581) and that for Gram-negatives was 52.4% (1353 of 2581). The rates of methicillin (oxacillin) resistance in Staphylococcus aureus and coagulase-negative staphylococci (CoNS) were 79% and 89%, respectively. About 45% of Streptococcus pneumoniae were resistant to trimethoprim-sulfamethoxazole and approximately 66% to penicillin. Among the Gram-negative isolates, Pseudomonas aeruginosa was most frequently isolated, representing 943 (36.7%) over five years. This possibly represents an unrecognized hospital outbreak or contamination of blood culture bottles or other products such as skin disinfectants. Additionally, this pathogen showed extremely high rates of antimicrobial resistance. There were notable differences in frequency of the five most common microorganisms isolated from blood cultures, which can help set priorities for focused infection control efforts. Conclusions: Our findings underscore the need to monitor blood culture isolates and their antimicrobial resistance patterns to observe resistance trends that would influence appropriate empiric treatment and infection control strategies for bacteremic children. Bloodstream infections (BSI) due to bacterial and fungal pathogens are a tremendously important cause of morbidity and mortality worldwide. To provide crucial information for the understanding of the spread of antibiotic resistance and encourage the prudent use of antibiotics, we reviewed the antimicrobial susceptibility patterns of bloodstream isolates in 25,223 blood cultures at Children Medical Center Hospital, Tehran, Iran from January 2001 to December 2005. Of 25,223 blood cultures examined in this investigation, 2581 (10.23 %) were positive for bacterial growth. The frequency of isolation of Gram-positive bacteria was 47.5% of all isolated microorganisms, and the remaining 52.5% were Gram negative. Overall, staphylococci were the most frequent group of organisms recovered from our blood cultures, comprising 1036 (40.1%) of all bacteria recovered from blood cultures. The rates of oxacillin resistance for S. aureus and Coagulase-negative staphylococci (CoNS) isolates were similar (86% versus 89%); however, the rate of S. aureus vancomycin resistance was almost twice that of CoNS resistance (35% versus 19%). About 45% of S. pneumoniae were resistant to Co-trimoxazole and approximately 73% to penicillin. P. aeruginosa was the first most common Gram-negative with 943 isolates evaluated. This pathogen showed extremely high rates of resistance to the majority of the antimicrobial agents tested. There were notable differences in the order of the five most common organisms isolated from blood cultures, which can help set priorities for focused control efforts. Our findings underscore the need to continue antimicrobial resistance surveillance programs, which can provide valuable insight into resistance trends. Bloodstream infections (BSI) due to bacterial and fungal pathogens are a tremendously important cause of morbidity and mortality worldwide. To provide crucial information for the understanding of the spread of antibiotic resistance and encourage the prudent use of antibiotics, we reviewed the antimicrobial susceptibility patterns of bloodstream isolates in 25,223 blood cultures at Children Medical Center Hospital, Tehran, Iran from January 2001 to December 2005. Of 25,223 blood cultures examined in this investigation, 2581 (10.23 %) were positive for bacterial growth. The frequency of isolation of Gram-positive bacteria was 47.5% of all isolated microorganisms, and the remaining 52.5% were Gram negative. Overall, staphylococci were the most frequent group of organisms recovered from our blood cultures, comprising 1036 (40.1%) of all bacteria recovered from blood cultures. The rates of oxacillin resistance for S. aureus and Coagulase-negative staphylococci (CoNS) isolates were similar (86% versus 89%); however, the rate of S. aureus vancomycin resistance was almost twice that of CoNS resistance (35% versus 19%). About 45% of S. pneumoniae were resistant to Co-trimoxazole and approximately 73% to penicillin. P. aeruginosa was the first most common Gram-negative with 943 isolates evaluated. This pathogen showed extremely high rates of resistance to the majority of the antimicrobial agents tested. There were notable differences in the order of the five most common organisms isolated from blood cultures, which can help set priorities for focused control efforts. Our findings underscore the need to continue antimicrobial resistance surveillance programs, which can provide valuable insight into resistance trends.

Journal ArticleDOI
TL;DR: Almost 20% of all patients with positive outcome during penicillin challenge are detected by adding p.o.7 with Penicillin to the original ENDA guidelines, which was extended to include a 7-day oral treatment for all patients who were negative in the ENDA programme.
Abstract: Many patients experience reactions during penicillin treatment. The diagnosis may be difficult and is mainly based on short-term tests. The European Network for Drug Allergy (ENDA) guidelines proposed for diagnosing penicillin allergy do not include long-term challenge. In this study a total of 405 patients were evaluated. The ENDA guidelines were extended, to include a 7-day oral treatment (p.o.7) with penicillin for all patients who were negative in the ENDA programme. Among the 405 patients; 85 had an immediate reaction to penicillin, and a further 13 reacted during p.o.7. Among the 307 patients with a negative outcome, 88 had a case history of reaction to other β-lactam antibiotics and were subsequently tested with the culprit drug. Thirteen patients had a positive outcome: 3 on single-dose challenge and 10 during p.o.7. The extended penicillin diagnostic work-up was positive in 111 patients, 30.0% showed immediate reactions and 5.7% reacted during p.o.7. Approximately 20% of all patients with positive outcome during penicillin challenge are detected by adding p.o.7 with penicillin to the original ENDA guidelines.

Journal ArticleDOI
TL;DR: Avoidance of cephalosporins may be recommended in cases of penicillin allergy, but newer generation cep HALsporins have demonstrate less cross-reactivity toPenicillin than earlier generation ones, and desensitization protocols for cep Halosporin are available but not standardized.
Abstract: Allergy to penicillin is the most commonly reported antibiotic allergy. However, most patients who report a positive history of a prior reaction to penicillin are not found to be allergic to penicillin upon skin testing. Often, this history is vague or based on a parent’s recollection of an event that occurred in the distant past. Avoidance of penicillin based on self-reported allergic history alone often leads to the use of an alternate antibiotic with greater cost or side effect profile. Patients with a negative skin test to both major and minor determinants may generally be given penicillin, with a statistical risk of developing an allergic reaction similar to that observed in the general population. A more cautious approach in these cases where the degree of suspicion is low, an allergic etiology is unproven, or there is a negative skin test, is to do a graded challenge. If the skin test is positive, an alternate antibiotic should be used. If, however, an alternate antibiotic is not available, then desensitization may be performed, but there are limitations to desensitization as well, and tolerance is not permanent. Avoidance of cephalosporins may be recommended in cases of penicillin allergy, but newer generation cephalosporins have demonstrate less cross-reactivity to penicillin than earlier generation ones. Desensitization protocols for cephalosporins are available but not standardized. The mechanisms of antibiotic sensitization are not clearly understood.

Book
19 May 2012

Journal ArticleDOI
TL;DR: The clinical practice of treating patients with gonorrhoea with an additional agent for presumptive Chlamydia trachomatis infection—particularly azithromycin and, to a lesser extent, doxycycline—may have prevented the appearance of treatment failures in those individuals infected with N gonor rhoeae strains possessing high cephalosporin MICs.
Abstract: The pattern of antimicrobial resistance in Neisseria gonorrhoeae is depressingly predictable. An antibiotic is chosen and used for a few years but resistance develops, so the dose is increased to maintain efficacy before the drug finally fails irrevocably. For penicillin, this process took a number of decades but with the subsequent use of tetracyclines, macrolides and fluoroquinolones, the cycle has shortened, and the utility of oral cephalosporins is now threatened within a few short years of their introduction as preferred therapy in many countries.1 Following the emergence of N gonorrhoeae strains with decreased susceptibility to oral cephalosporins, clinical treatment failures soon appeared in Japan and Hong Kong;2–4 more recently, similar outcomes have reported from other regions of the world, including Europe. There still exists some debate as to the minimum inhibitory concentration (MIC) breakpoint for oral cephalosporins that correlates with clinical failure. However, data from Deguchi et al suggest that clinical failures may occur with MICs of 0.125 mg/l or higher.3 Pharmacodynamic modelling with Monte Carlo simulations highlighted the fact that, for reliable efficacy, cephalosporins require a free drug level above the MIC for 20–24 h (compared to 7–10 h in the case of penicillin G).5 These analyses predicted that failures with standard doses of cefixime (400 mg) and ceftriaxone (250 mg) become likely around MICs of 0.125 mg/l and 0.25 mg/l respectively. The clinical practice of treating patients with gonorrhoea with an additional agent for presumptive Chlamydia trachomatis infection—particularly azithromycin and, to a lesser extent, doxycycline—may have prevented the appearance of treatment failures in those individuals infected with N gonorrhoeae strains possessing high cephalosporin MICs. The mechanism of resistance to oral cephalosporins involves changes in the structure and function of a number of key proteins, notably the penA -encoded penicillin binding protein …

Journal ArticleDOI
TL;DR: This review summarizes current knowledge on the results of this classical strain improvement process, and discusses avenues to improve β‐lactam biosynthesis and to exploit P. chrysogenum as an industrial host for the production of other antibiotics and peptide products.
Abstract: Industrial production of β-lactam antibiotics by the filamentous fungus Penicillium chrysogenum is based on successive classical strain improvement cycles. This review summarizes our current knowledge on the results of this classical strain improvement process, and discusses avenues to improve β-lactam biosynthesis and to exploit P. chrysogenum as an industrial host for the production of other antibiotics and peptide products. Genomic and transcriptional analysis of strain lineages has led to the identification of several important alterations in high-yielding strains, including the amplification of the penicillin biosynthetic gene cluster, elevated transcription of genes involved in biosynthesis of penicillin and amino acid precursors, and genes encoding microbody proliferation factors. In recent years, successful metabolic engineering and synthetic biology approaches have resulted in the redirection of the penicillin pathway towards the production of cephalosporins. This sets a new direction in industrial antibiotics productions towards more sustainable methods for the fermentative production of unnatural antibiotics and related compounds.

Journal ArticleDOI
TL;DR: The finding suggested that using the combination of sub-inhibitory concentrations of Au3+ and methicillin, erythromycin, nalidixic acid or vancomycin may be a promising new strategy for the treatment of highly resistant P. aeruginosa infections.
Abstract: Despite much success in drug design and development, Pseudomonas aeruginosa is still considered as one of the most problematic bacteria due to its ability to develop mutational resistance against a variety of antibiotics. In search for new strategies to enhance antibacterial activity of antibiotics, in this work, the combination effect of gold materials including trivalent gold ions (Au3+) and gold nanoparticles (Au NPs) with 14 different antibiotics was investigated against the clinical isolates of P. aeruginosa, Staphylococcus aureus and Escherichia coli. Disk diffusion assay was carried out, and test strains were treated with the sub-inhibitory contents of gold nanomaterial. Results showed that Au NPs did not increase the antibacterial effect of antibiotics at tested concentration (40 μg/disc). However, the susceptibility of resistant P. aeruginosa increased in the presence of Au3+ and methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid, up to 147 %. As an individual experiment, the same group of antibiotics was tested for their activity against clinical isolates of S. aureus, E. coli and a different resistant strain of P. aeruginosa in the presence of sub-inhibitory contents of Au3+, where Au3+ increased the susceptibility of test strains to methicillin, erythromycin, vancomycin, penicillin G, clindamycin and nalidixic acid. Our finding suggested that using the combination of sub-inhibitory concentrations of Au3+ and methicillin, erythromycin, nalidixic acid or vancomycin may be a promising new strategy for the treatment of highly resistant P. aeruginosa infections.

Journal ArticleDOI
TL;DR: The results suggest the importance of continued monitoring of A. pleuropneumoniae clinical isolates in order to choose the most appropriate treatment of infections and to control the increase of resistance to currently used antimicrobials.

Journal ArticleDOI
TL;DR: Increasing the disk diffusion zone size interpretive criteria to 35 mm for this antimicrobial/organism combination from the current 29-mm breakpoint may improve the sensitivity of phenotypic penicillin susceptibility testing.

Journal ArticleDOI
TL;DR: The development and validation of a simple method for the detection and quantification of six β-lactam antibiotics residues in bovine milk using a fast liquid–liquid extraction (LLE) and liquid chromatography-electrospray-tandem mass spectrometry (LC-MS/MS) are presented.
Abstract: This study presents the development and validation of a simple method for the detection and quantification of six β-lactam antibiotics residues (ceftiofur, penicillin G, penicillin V, oxacillin, cloxacillin and dicloxacillin) in bovine milk using a fast liquid-liquid extraction (LLE) for sample preparation, followed by liquid chromatography-electrospray-tandem mass spectrometry (LC-MS/MS). LLE consisted of the addition of acetonitrile to the sample, followed by addition of sodium chloride, centrifugation and direct injection of an aliquot into the LC-MS/MS system. Separation was performed in a C(18) column, using acetonitrile and water, both with 0.1% of formic acid, as mobile phase. Method validation was performed according to the criteria of Commission Decision 2002/657/EC. Limits of detection ranged from 0.4 (penicillin G and penicillin V) to 10.0 ng ml(-1) (ceftiofur), and linearity was achieved. The decision limit (CCα), detection capability (CCβ), accuracy, inter- and intra-day repeatability of the method are reported.

Journal Article
TL;DR: High rate of resistance to penicillin and amino glycosides is observed in the authors' tertiary care hospital and emergence of VRE has further worsened this situation, so, there is an urgent need for more rational and restricted use of antimicrobials.
Abstract: Aims: Enterococcus species are major nosocomial pathogen and are exhibiting vancomycin resistance with increasing frequency.Continouous monitoring and determination of antimicrobial susceptibility pattern is a necessacity.The present study aims to determine the prevalence and susceptibility pattern of Enterococci in tertiary care hospital. Methods and Material: Total of 92 enterococcal strains isolated from various samples were identified and speciated as per scheme of Facklam and Collins. Antibiotic susceptibility was determined for various drugs by Kirby bauer disc diffusion method. Results were interpreted as per CLSI guidelines and were even compared with Vitek2 automated system. Results: 69 strains were E.faecalis, 21 were E.faecium and two were E.gallinarum. High level resistance to penicillin, ampicillin, gentamicin and streptomycin were observed. All strains were sensitive to linezolid and teicoplanin.8% strains showed vancomycin resistance which was detected by Vitek2 automated system. Conclusions: High rate of resistance to penicillin and amino glycosides is observed in our tertiary care hospital and emergence of VRE has further worsened this situation. So, there is an urgent need for more rational and restricted use of antimicrobials.

Journal ArticleDOI
TL;DR: In recent decades, the prevalence and rate of penicillin resistance and non-susceptibility among Streptococcus pneumoniae isolates have increased in Saudi Arabia and the organism remains, however, susceptible to other beta-lactams and to quinolones.
Abstract: Several species of Gram-positive cocci are major nosocomial or community pathogens associated with morbidity and mortality. Here, we review the antimicrobial resistance among these pathogens in Saudi Arabia. In the last decades, antimicrobial resistance has increased among Staphylococcus aureus in the Kingdom with a growing prevalence of both nosocomial and community methicillin-resistant S. aureus (MRSA) isolates. As yet, no vancomycin-resistant MRSA have been reported, although isolates with reduced susceptibility to the drug have been noted. Currently, the prevalence of vancomycin-resistant entrococci (VRE) is low; however, VRE has been described in the Kingdom as well as Enterococcus faecalis and E. faecium isolates with high-level resistance to penicillin, sulfamethoxazole, macrolides, tetracycline, and aminoglycosides. In recent decades, the prevalence and rate of penicillin resistance and non-susceptibility among Streptococcus pneumoniae isolates have increased in Saudi Arabia. The organism...

Journal ArticleDOI
TL;DR: Newer promising anti-gram-positive bacterial drugs with activity against methicillin-resistant staphylococci include daptomycin, linezolid, tigecycline and telavancin, however, toxicity concerns, limited data in immunocompromised populations and high cost prevent the widespread use of these drugs among patients with cancer.
Abstract: Bacterial infections, particularly those due to gram-positive bacteria, continue to predominate in patients with cancer. Coagulase-negative and coagulase-positive staphylococci and enterococci remain as common pathogenic microorganisms. Clostridium diffi cile has emerged as a signifi cant pathogen. Major clinical syndromes include vascular catheter-related infection, febrile neutropenia, diarrhea and colitis. Rising antimicrobial resistance among gram-positive bacteria is of serious concern. The clinical utility of penicillin against streptococci and vancomycin against coagulase-negative and coagulase-positive staphylococci and enterococci may be rapidly diminishing. Liberal empiric use of vancomycin during neutropenic fever needs careful reconsideration. Newer promising anti-gram-positive bacterial drugs with activity against methicillin-resistant staphylococci include daptomycin, linezolid, tigecycline and telavancin. However, toxicity concerns, limited data in immunocompromised populations and high cost prevent the widespread use of these drugs among patients with cancer.

Journal ArticleDOI
TL;DR: In this article, an electronic physician survey was sent to 623 providers in allergy, internal medicine, pediatrics, and family medicine, querying beta-lactam use in patients with a history of penicillin allergy.
Abstract: Beta-lactam antibiotics are widely used, but hypersensitivity reactions are common and difficult to manage. This study was designed to identify lack of knowledge regarding the safe use of alternative beta-lactams in penicillin-allergic patients and assess management differences between allergists and nonallergists. An electronic physician survey was sent to 623 providers in allergy, internal medicine, pediatrics, and family medicine, querying beta-lactam use in patients with a history of penicillin allergy. A total of 110 (17.7%) surveys were completed. For patients with a prior maculopapular rash to penicillin, most providers were uncomfortable prescribing penicillins again, although they would use other beta-lactams. In patients with an exfoliative dermatitis to penicillin, 46% of responders would not prescribe any beta-lactam again. For patients with a positive skin test to penicillin, only 45.1% of nonallergists were comfortable prescribing monobactams versus 62.5% of allergists; 30.3% of all responders would give a carbapenem. In patients with urticaria to penicillin, pediatricians were the most comfortable prescribing third- or fourth-generation cephalosporins. Providers (both allergists and nonallergists) were unfamiliar with the safety of prescribing penicillin in patients with history of maculopapular rash, the safety of monobactams, and low cross-reactivity with carbapenems in penicillin-allergic individuals. Nonallergists were also unfamiliar with the usefulness of penicillin skin testing. Improved education is needed to address these areas. Additionally, we found variability in responses regarding exfoliative dermatitis and comfort prescribing cephalosporins in patients with suspected IgE-mediated drug allergy to penicillin, highlighting the need for additional research in these areas.