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Showing papers on "Penicillin published in 2020"


Journal ArticleDOI
TL;DR: The different classes of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams and penems) are discussed in light of their stability, sensitivity to β- lactamases, mechanism of action and spectrum of antimicrobial activity.

154 citations


Journal ArticleDOI
01 Feb 2020-Allergy
TL;DR: Operationalizing penicillin allergy de‐labeling into a new arm of antimicrobial stewardship programs (ASPs) has become an increasing global focus.
Abstract: Background Even though 8%‐25% of most populations studied globally are labeled as penicillin allergic, most diagnoses of penicillin allergy are made in childhood and relate to events that are either not allergic in nature, are low risk for immediate hypersensitivity, or are a potential true allergy that has waned over time. Penicillin allergy labels directly impact antimicrobial stewardship by leading to use of less effective and broader spectrum antimicrobials and are associated with antimicrobial resistance. They may also delay appropriate antimicrobial therapy and lead to increased risk of specific adverse healthcare outcomes. Operationalizing penicillin allergy de‐labeling into a new arm of antimicrobial stewardship programs (ASPs) has become an increasing global focus. Methods We performed an evidence‐based narrative review of the literature of penicillin allergy label carriage, the adverse effects of penicillin allergy labels, and current approaches and barriers to penicillin allergy de‐labeling. Over the period 1928‐2018 in Pubmed and Medline, search terms used included “penicillin allergy” or “penicillin hypersensitivity” alone or in combination with “adverse events,” “testing,” “evaluation,” “effects,” “label,” “de‐labeling,” “prick or epicutaneous,” and “intradermal” skin testing, “oral challenge or provocation,” “cross‐reactivity,” and “antimicrobial stewardship”. Results Penicillin allergy labels are highly prevalent, largely inaccurate and their carriage may lead to unnecessary treatment and inferior outcomes with alternative agents as well as adverse public health outcomes such as antibiotic resistance. Conclusions Operationalizing penicillin allergy de‐labeling as an aspect of ASP has become an increasing global focus. There is a need for validated approaches that optimally combine the use of history and ingestion challenge with or without proceeding formal skin testing to tackle penicillin allergy efficiently within complex healthcare systems. At the same time, there is great promise for penicillin allergy evaluation and de‐labeling as an individual and public health strategy to reduce adverse healthcare outcomes, improve antimicrobial stewardship, and decrease healthcare costs.

120 citations


Journal ArticleDOI
TL;DR: The results suggest that a PEN-FAST score of less than 3, associated with a high negative predictive value, could be used by clinicians and antimicrobial stewardship programs to identify low-risk penicillin allergies at the point of care.
Abstract: Importance Penicillin allergy is a significant public health issue for patients, antimicrobial stewardship programs, and health services. Validated clinical decision rules are urgently needed to identify low-risk penicillin allergies that potentially do not require penicillin skin testing by a specialist. Objective To develop and validate a penicillin allergy clinical decision rule that enables point-of-care risk assessment of patient-reported penicillin allergies. Design, Setting, and Participants In this diagnostic study, a multicenter prospective antibiotic allergy–tested cohort of 622 patients from 2 tertiary care sites in Melbourne, Australia (Austin Health and Peter MacCallum Cancer Centre) was used for derivation and internal validation of a penicillin allergy decision rule. Backward stepwise logistic regression was used to derive the model, including clinical variables predictive of a positive penicillin allergy test result. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in retrospective penicillin allergy–tested cohorts consisting of 945 patients from Sydney and Perth, Australia, and Nashville, Tennessee. Patients who reported a penicillin allergy underwent penicillin allergy testing using skin prick, intradermal, or patch testing and/or oral challenge (direct or after skin testing). Data were collected from June 26, 2008, to June 3, 2019, and analyzed from January 9 to 12, 2019. Main Outcomes and Measures The primary outcome for the model was any positive result of penicillin allergy testing performed during outpatient or inpatient assessment. Results From an internal derivation and validation cohort of 622 patients (367 female [59.0%]; median age, 60 [interquartile range{IQR}, 48-71] years) and an external validation cohort of 945 patients (662 female [70.1%]; median age, 55 [IQR, 38-68] years), the 4 features associated with a positive penicillin allergy test result on multivariable analysis were summarized in the mnemonic PEN-FAST:penicillin allergy,five or fewer years ago,anaphylaxis/angioedema,severe cutaneous adverse reaction (SCAR), andtreatment required for allergy episode. The major criteria included an allergy event occurring 5 or fewer years ago (2 points) and anaphylaxis/angioedema or SCAR (2 points); the minor criterion (1 point), treatment required for an allergy episode. Internal validation showed minimal mean optimism of 0.003 with internally validated area under the curve of 0.805. A cutoff of less than 3 points for PEN-FAST was chosen to classify a low risk of penicillin allergy, for which only 17 of 460 patients (3.7%) had positive results of allergy testing, with a negative predictive value of 96.3% (95% CI, 94.1%-97.8%). External validation resulted in similar findings. Conclusions and Relevance In this study, PEN-FAST was found to be a simple rule that accurately identified low-risk penicillin allergies that do not require formal allergy testing. The results suggest that a PEN-FAST score of less than 3, associated with a high negative predictive value, could be used by clinicians and antimicrobial stewardship programs to identify low-risk penicillin allergies at the point of care.

104 citations


Journal ArticleDOI
TL;DR: A comprehensive analysis of the prevalence of antibiotic resistance in Group B Streptococcus is provided and the specific resistance mechanisms identified in GBS isolates to date are outlined.
Abstract: Group B Streptococcus (GBS) is the leading cause of neonatal disease worldwide, and invasive disease in adults is becoming more prevalent. Currently, some countries adopt an intrapartum antibiotic prophylaxis regime to help prevent the transmission of GBS from mother to neonate during delivery. This precaution has reduced the incidence of GBS-associated early-onset disease; however, rates of late-onset disease and stillbirths associated with GBS infections remain unchanged. GBS is still recognized as being universally susceptible to beta-lactam antibiotics; however, there have been reports of reduced susceptibility to beta-lactams, including penicillin, in some countries. Resistance to second-line antibiotics, such as erythromycin and clindamycin, remains high amongst GBS, with several countries noting increased resistance rates in recent years. Moreover, resistance to other antibiotic classes, such as fluoroquinolones and aminoglycosides, also continues to rise. In instances where patients are allergic to penicillin and second-line antibiotics are ineffective, vancomycin is administered. While vancomycin, a last resort antibiotic, still remains largely effective, there have been two documented cases of vancomycin resistance in GBS. This review provides a comprehensive analysis of the prevalence of antibiotic resistance in GBS and outlines the specific resistance mechanisms identified in GBS isolates to date.

55 citations


Journal ArticleDOI
TL;DR: Outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.
Abstract: The preparation and characterization of ionic liquids and organic salts (OSILs) that contain anionic penicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichia coli and Staphylococcus aureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxide salts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C2OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C16Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.

46 citations


Journal ArticleDOI
TL;DR: Abundance and antibiotic resistance of bacteria of the genus Aeromonas isolated from the water of three carp ponds were studied in this article, which showed that planktonic aeromonas inhabiting those ponds strongly differed in the resistance level to tested antibiotics.
Abstract: Abundance and antibiotic resistance of bacteria of the genus Aeromonas isolated from the water of three carp ponds were studied. The number of those bacteria differed between the studied ponds, sites and season. The results of the present study showed that planktonic Aeromonas inhabiting those ponds strongly differed in the resistance level to tested antibiotics. These microorganisms were the most resistant to amoxicillin, ampicillin, clindamycin and penicillin. However, all isolates Aeromonas were susceptible to gentamycin and streptomycin. Majority of bacterial strains were characterized by resistance to 4-6 of the 12 antibiotics tested. Bacterial resistance to antibiotics depended on their chemical structure. Aeromonas strains isolated from the studied ponds were the most resistant to β-lactam and lincosamides antibiotics, while the most susceptible to aminoglycosides, chloramphenicols and fluoroquinolones.

45 citations


Journal ArticleDOI
TL;DR: Understanding the evolution of antibiotic resistance at the molecular level as a functional tool for bioinformatic-based drug design is an important step in the fight against antibiotic resistance.
Abstract: The use of antibiotics to manage infectious diseases dates back to ancient civilization, but the lack of a clear distinction between the therapeutic and toxic dose has been a major challenge. This precipitates the notion that antibiotic resistance was from time immemorial, principally because of a lack of adequate knowledge of therapeutic doses and continuous exposure of these bacteria to suboptimal plasma concentration of antibiotics. With the discovery of penicillin by Alexander Fleming in 1924, a milestone in bacterial infections' treatment was achieved. This forms the foundation for the modern era of antibiotic drugs. Antibiotics such as penicillins, cephalosporins, quinolones, tetracycline, macrolides, sulphonamides, aminoglycosides and glycopeptides are the mainstay in managing severe bacterial infections, but resistant strains of bacteria have emerged and hampered the progress of research in this field. Recently, new approaches to research involving bacteria resistance to antibiotics have appeared; these involve combining the molecular understanding of bacteria systems with the knowledge of bioinformatics. Consequently, many molecules have been developed to curb resistance associated with different bacterial infections. However, because of increased emphasis on the clinical relevance of antibiotics, the synergy between in silico study and in vivo study is well cemented and this facilitates the discovery of potent antibiotics. In this review, we seek to give an overview of earlier reviews and molecular and structural understanding of bacteria resistance to antibiotics, while focusing on the recent bioinformatics approach to antibacterial drug discovery.

36 citations



Journal ArticleDOI
TL;DR: In this article, the detection of penicillin-resistant and ciprofloxacin-resistant N meningitidis serogroup Y (NmY) isolates in the United States was described.
Abstract: Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts Historically, N meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin This report describes detection of penicillin-resistant and ciprofloxacin-resistant N meningitidis serogroup Y (NmY) isolates in the United States NmY isolates containing a blaROB-1 β-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020 Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA) Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013 Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations

32 citations


Journal ArticleDOI
TL;DR: Clostridioides difficile infection was more common after parenteral exposures, and with extended-spectrum penicillins, beta lactamase combinations, carbapenems, monobactam, and clindamycin exposures compared to oral penicllins or clind amycin.

31 citations


Journal ArticleDOI
TL;DR: Robust evidence is presented for the role of an allele of the major histocompatibility complex I gene HLA-B in the occurrence of penicillin allergy.
Abstract: Summary Hypersensitivity reactions to drugs are often unpredictable and can be life threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown. We extracted data from the electronic health records of more than 600,000 participants from the UK, Estonian, and Vanderbilt University Medical Center’s BioVU biobanks to study the role of genetic variation in the occurrence of self-reported penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from these cohorts to further fine map the human leukocyte antigen (HLA) association and replicated our results in 23andMe’s research cohort involving a total of 1.12 million individuals. Genome-wide meta-analysis of penicillin allergy revealed two loci, including one located in the HLA region on chromosome 6. This signal was further fine-mapped to the HLA-B∗55:01 allele (OR 1.41 95% CI 1.33–1.49, p value 2.04 × 10−31) and confirmed by independent replication in 23andMe’s research cohort (OR 1.30 95% CI 1.25–1.34, p value 1.00 × 10−47). The lead SNP was also associated with lower lymphocyte counts and in silico follow-up suggests a potential effect on T-lymphocytes at HLA-B∗55:01. We also observed a significant hit in PTPN22 and the GWAS results correlated with the genetics of rheumatoid arthritis and psoriasis. We present robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.

Journal ArticleDOI
TL;DR: Two broad-spectrum bacteriocins acted synergistically with each other and with penicillin G in killing MRSA in vitro, demonstrating that the three-component formulation was efficient in eradicating the pathogen from treated wounds.
Abstract: The emergence of antibiotic resistant pathogens has caused a serious world-wide problem in infection treatments in recent years. One of these pathogens is the methicillin-resistant Staphylococcus aureus (MRSA) which is a major cause of skin and soft tissue infections. Alternative strategies and novel sources of antimicrobials to solve antibiotic resistance problems are urgently needed. In this study, we explored the potential of two broad-spectrum bacteriocins, garvicin KS and micrococcin P1, in skin infection treatments. These two bacteriocins were acting synergistically with each other and with penicillin G in killing MRSA in vitro. The minimum inhibitory concentration (MIC) of the antimicrobials in the three-component mixture was 40 ng/ml for micrococcin P1 and 2 μg/ml for garvicin KS and penicillin G, which were 62, 16 and at least 1250 times less when compared to their MICs when assessed individually. To assess its therapeutic potential further, we challenged this three-component formulation in a murine skin infection model with the multidrug-resistant luciferase-tagged MRSA Xen31, a strain derived from the clinical isolate S. aureus ATCC 33591. Using the tagged luciferase activity as a reporter for the presence of Xen31 in wounds, we evidently demonstrated that the three-component formulation was efficient to eradicate the pathogen from treated wounds. Furthermore, compared to Fucidin cream which is an antibiotic commonly used in skin infection treatments, our formulation was also superior in terms of preventing resistance development.

Journal ArticleDOI
TL;DR: The high frequency of potentially pathogenic MDR S. aureus in milk samples intended for human consumption, demonstrates the public health relevance of this pathogen in the region.
Abstract: Background: Biofilm formation in S. aureus may reduce the rate of penetration of antibiotics, thereby complicating treatment of infections caused by these bacteria. The aim of this study was to correlate biofilm-forming potentials, antimicrobial resistance, and genes in S. aureus isolates. Methods: A total of 64 milk samples were analysed, and 77 S. aureus were isolated. Results: Seventy (90.9%) isolates were biofilm producers. The ica biofilm-forming genes were detected among 75.3% of the isolates, with icaA being the most prevalent (49, 63.6%). The icaB gene was significantly (P = 0.027) higher in isolates with strong biofilm formation potentials. High resistance (60%–90%) of the isolates was observed against ceftriaxone, vancomycin, and penicillin, and 25 (32.5%) of S. aureus showed multidrug resistance (MDR) to at least three antibiotics. Five resistance genes, namely blaZ (29, 37.7%), vanC (29, 37.7%), tetK (24, 31.2%), tetL (21, 27.3%), and msrA/B (16, 20.8%) were detected. Most MDR phenotypes possessed at least one resistance gene alongside the biofilm genes. However, no distinct pattern was identified among the resistance and biofilm phenotypes. Conclusions: The high frequency of potentially pathogenic MDR S. aureus in milk samples intended for human consumption, demonstrates the public health relevance of this pathogen in the region.

Journal ArticleDOI
25 Apr 2020
TL;DR: The penicillin biosynthesis finding shows that in order to increase biosynthesis of novel secondary metabolites it is essential to adequately target enzymes to organelles.
Abstract: Fungal secondary metabolites are synthesized by complex biosynthetic pathways catalized by enzymes located in different subcellular compartments, thus requiring traffic of precursors and intermediates between them. The β-lactam antibiotics penicillin and cephalosporin C serve as an excellent model to understand the molecular mechanisms that control the subcellular localization of secondary metabolites biosynthetic enzymes. Optimal functioning of the β-lactam biosynthetic enzymes relies on a sophisticated temporal and spatial organization of the enzymes, the intermediates and the final products. The first and second enzymes of the penicillin pathway, ACV synthetase and IPN synthase, in Penicillium chrysogenum and Aspergillus nidulans are cytosolic. In contrast, the last two enzymes of the penicillin pathway, phenylacetyl-CoA ligase and isopenicillin N acyltransferase, are located in peroxisomes working as a tandem at their optimal pH that coincides with the peroxisomes pH. Two MFS transporters, PenM and PaaT have been found to be involved in the import of the intermediates isopenicillin N and phenylacetic acid, respectively, into peroxisomes. Similar compartmentalization of intermediates occurs in Acremonium chrysogenum; two enzymes isopenicillin N-CoA ligase and isopenicillin N-CoA epimerase, that catalyse the conversion of isopenicillin N in penicillin N, are located in peroxisomes. Two genes encoding MFS transporters, cefP and cefM, are located in the early cephalosporin gene cluster. These transporters have been localized in peroxisomes by confocal fluorescence microscopy. A third gene of A. chrysogenum, cefT, encodes an MFS protein, located in the cell membrane involved in the secretion of cephalosporin C, although cefT-disrupted mutants are still able to export cephalosporin by redundant transporters. The secretion of penicillin from peroxisomes to the extracellular medium is still unclear. Attempts have been made to identify a gene encoding the penicillin secretion protein among the 48 ABC-transporters of P. chrysogenum. The highly efficient secretion system that exports penicillin against a concentration gradient may involve active penicillin extrusion systems mediated by vesicles that fuse to the cell membrane. However, there is no correlation of pexophagy with penicillin or cephalosporin formation since inactivation of pexophagy leads to increased penicillin or cephalosporin biosynthesis due to preservation of peroxisomes. The penicillin biosynthesis finding shows that in order to increase biosynthesis of novel secondary metabolites it is essential to adequately target enzymes to organelles.

Journal ArticleDOI
TL;DR: The ability to acquire detailed antimicrobial resistance information directly from molecular data will facilitate the transition to whole-genome sequencing analysis from phenotypic testing and can fill the surveillance gap in an era of increased reliance on nucleic acid assay testing (NAAT) diagnostics.
Abstract: The emergence of Neisseria gonorrhoeae strains that are resistant to azithromycin and extended-spectrum cephalosporins represents a public health threat, that of untreatable gonorrhea infections. Multivariate regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to the overall antimicrobial MICs for ceftriaxone, cefixime, azithromycin, tetracycline, ciprofloxacin, and penicillin. A training data set consisting of 1,280 N. gonorrhoeae strains was used to generate regression equations which were then applied to validation data sets of Canadian (n = 1,095) and international (n = 431) strains. The predicted MICs for extended-spectrum cephalosporins (ceftriaxone and cefixime) were fully explained by 5 amino acid substitutions in PenA, A311V, A501P/T/V, N513Y, A517G, and G543S; the presence of a disrupted mtrR promoter; and the PorB G120 and PonA L421P mutations. The correlation of predicted MICs within one doubling dilution to phenotypically determined MICs of the Canadian validation data set was 95.0% for ceftriaxone, 95.6% for cefixime, 91.4% for azithromycin, 98.2% for tetracycline, 90.4% for ciprofloxacin, and 92.3% for penicillin, with an overall sensitivity of 99.9% and specificity of 97.1%. The correlations of predicted MIC values to the phenotypically determined MICs were similar to those from phenotype MIC-only comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular data will facilitate the transition to whole-genome sequencing analysis from phenotypic testing and can fill the surveillance gap in an era of increased reliance on nucleic acid assay testing (NAAT) diagnostics to better monitor the dynamics of N. gonorrhoeae.

Journal ArticleDOI
29 Apr 2020
TL;DR: The relative frequency of PBP sequence variation within a global database of 9,667 S. pyogenes isolates indicated that while heavy antibiotic pressure may select for mutations in the PBPs, there is currently no evidence of such mutations becoming fixed in the S.pyogenes population or that mutations are being sequentially acquired in thePBPs.
Abstract: A recent clinical report has linked Streptococcus pyogenes β-lactam antibiotic resistance to mutation in the penicillin binding protein (PBP) PBP2x. To determine whether this is an isolated case or reflects a broader prevalence of mutations that might confer reduced β-lactam susceptibility, we investigated the relative frequency of PBP sequence variation within a global database of 9,667 S. pyogenes isolates. We found that mutations in S. pyogenes PBPs (PBP2x, PBP1a, PBP1b, and PBP2a) occur infrequently across this global database, with fewer than 3 amino acid changes differing between >99% of the global population. Only 4 of the 9,667 strains contained mutations near transpeptidase active sites of PBP2x or PBP1a. The reported PBP2x T553K substitution was not identified. These findings are in contrast to those of 2,520 S. pneumococcus sequences where PBP mutations are relatively frequent and are often located in key β-lactam binding pockets. These data, combined with the general lack of penicillin resistance reported in S. pyogenes worldwide, suggests that extensive, unknown constraints restrict S. pyogenes PBP sequence plasticity. Our findings imply that while heavy antibiotic pressure may select for mutations in the PBPs, there is currently no evidence of such mutations becoming fixed in the S. pyogenes population or that mutations are being sequentially acquired in the PBPs.IMPORTANCE β-Lactam antibiotics are the first-line therapeutic option for Streptococcus pyogenes infections. Despite the global high prevalence of S. pyogenes infections and widespread use of β-lactams worldwide, reports of resistance to β-lactam antibiotics, such as penicillin, have been incredibly rare. Recently, β-lactam resistance, as defined by clinical breakpoints, was detected in two clinical S. pyogenes isolates with accompanying mutations in the active site of the penicillin binding protein PBP2x, raising concerns that β-lactam resistance will become more widespread. We screened a global database of S. pyogenes genome sequences to investigate the frequency of PBP mutations, identifying that PBP mutations are uncommon relative to those of Streptococcus pneumoniae These findings support clinical observations that β-lactam resistance is rare in S. pyogenes and suggest that there are considerable constraints on S. pyogenes PBP sequence variation.

Journal ArticleDOI
02 Dec 2020
TL;DR: It is shown that a combination of two bacteriocins with distinct structural and functional characteristics, garvicin KS, and micrococcin P1, showed a synergetic antibacterial activity against biofilms produced in vitro by S. aureus, including several MRSA strains.
Abstract: Antibiotic-resistant and biofilm-associated infections brought about by methicillin-resistant Staphylococcus aureus (MRSA) strains is a pressing issue both inside as well as outside nosocomial environments worldwide. Here, we show that a combination of two bacteriocins with distinct structural and functional characteristics, garvicin KS, and micrococcin P1, showed a synergetic antibacterial activity against biofilms produced in vitro by S. aureus, including several MRSA strains. In addition, this bacteriocin-based antimicrobial combination showed the ability to restore the sensitivity of the highly resilient MRSA strain ATCC 33591 to the β-lactam antibiotic penicillin G. By using a combination of bacterial cell metabolic assays, confocal and scanning electron microscopy, we show that the combination between garvicin KS, micrococcin P1, and penicillin G potently inhibit cell viability within S. aureus biofilms by causing severe cell damage. Together these data indicate that bacteriocins can be valuable therapeutic tools in the fight against biofilm-associated MRSA infections.

Journal ArticleDOI
TL;DR: This work serves as an initial exploration into the resistance-encoding mutations harbored by nonpathogenic Neisseria, which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired by N. gonorrhoeae.
Abstract: Nonpathogenic Neisseria transfer mutations encoding antibiotic resistance to their pathogenic relative Neisseria gonorrhoeae. However, the resistance genotypes and subsequent phenotypes of nonpathogens within the genus have been described infrequently. Here, we characterize the minimum inhibitory concentrations (MICs) of a panel of Neisseria (n = 26)-including several commensal species-to a suite of diverse antibiotics. We furthermore use whole genome sequencing and the Comprehensive Antibiotic Resistance Database Resistance Gene Identifier (RGI) platform to predict putative resistance-encoding mutations. Resistant isolates to all tested antimicrobials including penicillin (n = 5/26), ceftriaxone (n = 2/26), cefixime (n = 3/26), tetracycline (n = 10/26), azithromycin (n = 11/26), and ciprofloxacin (n = 4/26) were found. In total, 63 distinct mutations were predicted by RGI to be involved in resistance. The presence of several mutations had clear associations with increased MIC such as DNA gyrase subunit A (gyrA) (S91F) and ciprofloxacin, tetracycline resistance protein (tetM) and 30S ribosomal protein S10 (rpsJ) (V57M) and tetracycline, and TEM-type β-lactamases and penicillin. However, mutations with strong associations to macrolide and cephalosporin resistance were not conclusive. This work serves as an initial exploration into the resistance-encoding mutations harbored by nonpathogenic Neisseria, which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired by N. gonorrhoeae.

Journal ArticleDOI
TL;DR: Data from the literature is shown which suggests the presence of S. pyogenes isolates that are not susceptible to β-lactam antibiotics and whether these strains are really nonsusceptible to β -lactAM antibiotics and the presenceof mutation in the pbp2x gene requires further research and confirmation.
Abstract: Streptococcus pyogenes is regarded as susceptible to β-lactam antibiotics. The guidelines of the Clinical and Laboratory Standards Institute (CLSI) are widely recognized and have long-recommended penicillin for treatment of S. pyogenes infections. There is no CLSI guideline for the treatment of S. pyogenes infections that have intermediate susceptibility or resistance to penicillin. However, there have been several reports of S. pyogenes isolates that are nonsusceptible or even resistant to β-lactam antibiotics, mostly from Chinese journals. The purpose of this commentary is to show data from the literature which suggests the presence of S. pyogenes isolates that are not susceptible to β-lactam antibiotics and whether these strains are really nonsusceptible to β-lactam antibiotics and the presence of mutation in the pbp2x gene requires further research and confirmation.

Journal ArticleDOI
TL;DR: The high frequency of adhesin and toxin genes in MRSA indicates their potential virulence in bovine mastitis in China and should lead to calls for antibiogram analysis before antimicrobial therapy.

Journal ArticleDOI
TL;DR: It is demonstrated that the known prevalence of true penicillin allergy extends to pregnant women and PST and desensitization can be safely applied during pregnancy and are tools that should be used more frequently.
Abstract: Objective This study sought to evaluate available evidence of the safety of penicillin skin testing (PST), challenge, and desensitization in pregnancy, with efforts to improve perinatal care for patients with a penicillin allergy history and mitigate the negative sequelae of unverified penicillin allergy labels. Methods A systematic review of studies was conducted using Cochrane Library, Medline, EMBASE, and International Pharmaceutical Abstracts. Included were peer-reviewed studies without date restrictions, published in English or French, relating to PST, challenge, or desensitization in pregnancy. Editorials, opinion pieces, and letters were excluded. Review authors independently screened citations and full-text articles, extracted data, and conducted quality assessment. Given the heterogeneity of study designs, a narrative synthesis was conducted. Results The search identified 1195 references, of which 18 studies met inclusion criteria. In total there were 231 patients with varying histories of penicillin allergy, the majority requiring treatment for syphilis or group B streptococcal (GBS) disease during pregnancy. Of the 203 participants who underwent PST, 83.7% had negative test results. Allergy-related reactions were rare in PST (1.5%) and challenge (0%), and although these reactions were more common in desensitization (19.7%), most were benign. Among the 231 cases, only one adverse pregnancy outcome was reported (0.4%). Conclusion This review demonstrates that the known prevalence of true penicillin allergy extends to pregnant women. PST and desensitization can be safely applied during pregnancy and are tools that should be used more frequently. Further data on the safety of challenge during pregnancy are recommended.

Journal ArticleDOI
TL;DR: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce, so the use of a quadruple therapy with PPI, bismuth, tetracycline, and M has been recommended.
Abstract: Background: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. Aim: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the “European Registry of H pylori management” (Hp-EuReg). Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. Results: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera®; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. Conclusion: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Journal ArticleDOI
TL;DR: It is shown that PBP3 activity localizes as patches in single cells and concentrates as a ring at the septum and the division site during the cell growth cycle, which was not possible with previous chemical and biological approaches.
Abstract: Selective chemical probes enable individual investigation of penicillin-binding proteins (PBPs) and provide critical information about their enzymatic activity with spatial and temporal resolution. To identify scaffolds for novel probes to study peptidoglycan biosynthesis in Bacillus subtilis, we evaluated the PBP inhibition profiles of 21 β-lactam antibiotics from different structural subclasses using a fluorescence-based assay. Most compounds readily labeled PBP1, PBP2a, PBP2b, or PBP4. Almost all penicillin scaffolds were coselective for all or combinations of PBP2a, 2b, and 4. Cephalosporins, on the other hand, possessed the lowest IC50 values for PBP1 alone or along with PBP4 (ceftriaxone, cefoxitin) and 2b (cefotaxime) or 2a, 2b, and 4 (cephalothin). Overall, five selective inhibitors for PBP1 (aztreonam, faropenem, piperacillin, cefuroxime, and cefsulodin), one selective inhibitor for PBP5 (6-aminopenicillanic acid), and various coselective inhibitors for other PBPs in B. subtilis were discovered. Surprisingly, carbapenems strongly inhibited PBP3, formerly shown to have low affinity for β-lactams and speculated to be involved in β-lactam resistance in B. subtilis. To investigate the specific roles of PBP3, we developed activity-based probes based on the meropenem core and utilized them to monitor the activity of PBP3 in living cells. We showed that PBP3 activity localizes as patches in single cells and concentrates as a ring at the septum and the division site during the cell growth cycle. Our activity-based approach enabled spatial resolution of the transpeptidation activity of individual PBPs in this model microorganism, which was not possible with previous chemical and biological approaches.


Journal ArticleDOI
TL;DR: The results show a low prevalence of antibiotic multidrug resistance in S. aureus isolates, even if the detection of selected antimicrobial resistance genes did not always correspond with the occurrence of phenotypic antibiotic resistance; the immune evasion cluster gene prevalence was quite low in the samples analyzed.


Journal ArticleDOI
TL;DR: In a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ∼90% cases, which should result in reduced incidence of renal failure, an important prognostic factor in IE.

Journal ArticleDOI
TL;DR: A higher risk of postoperative infection is found after prophylactic use of intravenous clindamycin antibiotic after shoulder arthroplasty after surgery for patients with penicillin allergy.
Abstract: Background This study determines whether infection rates differ between prophylactic antibiotic use for patients with or without penicillin allergy before shoulder arthroplasty surgery. Methods Seven thousand one hundred forty primary shoulder arthroplasties operated between 2005 and 2016 were identified. We compared deep surgical site infection risk of patients who received perioperative vancomycin alone (6.2%, N = 444) or clindamycin alone (7.1%, N = 508) for penicillin allergy versus patients who received cefazolin alone without penicillin allergy (86.7%, N = 6,188). Results Seventy deep infections (1.2% 5-year cumulative incidence) were observed. The most common organism was Cutibacterium acnes (39.4%, N = 27). Compared with patients treated with cefazolin, infection risk was not different for those treated with vancomycin (hazard ratio = 1.17, 95% confidence interval 0.42 to 3.30, P = 0.8), but a higher risk of infection was identified for those treated with clindamycin alone (hazard ratio = 3.45, 95% confidence interval 1.84 to 6.47, P Conclusion A higher risk of postoperative infection is found after prophylactic use of intravenous clindamycin antibiotic after shoulder arthroplasty. Vancomycin is preferred over clindamycin for patients with penicillin allergy. Level of evidence III, retrospective cohort study.

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TL;DR: In patients with such hypersensitivity who need these alternative β-lactams, pretreatment skin tests are advisable because of the possibility of coexisting sensitivities or, much less frequently, of a sensitivity to an antigenic determinant of the common β- lactam ring.

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TL;DR: DC is a safe, effective, and less expensive method for penicillin de-labeling in adult inpatients with a low risk, cutaneous-only reaction history >20 years ago.