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141. Mutations in Genes Encoding Penicillin-Binding Proteins and Efflux Pumps Play a Role in β-Lactam Resistance in <i>Helicobacter cinaedi</i>. Full Text available with Trip Pro

Mutations in Genes Encoding Penicillin-Binding Proteins and Efflux Pumps Play a Role in β-Lactam Resistance in Helicobacter cinaedi. β-Lactams are often used to treat Helicobacter cinaedi infections; however, the mechanism underlying β-lactam resistance is unknown. In this study, we investigated β-lactam resistance in an H. cinaedi strain, MRY12-0051 (MICs of amoxicillin [AMX] and ceftriaxone [CRO], 32 and 128 μg/ml; obtained from human feces). Based on a comparative whole-genome (...) analysis of MRY12-0051 and the CRO-susceptible H. cinaedi strain MRY08-1234 (MICs of AMX and CRO, 1 and 4 μg/ml; obtained from human blood), we identified five mutations in genes encoding penicillin-binding proteins (PBPs), including two in pbpA, one in pbp2, and two in ftsI Transformation and penicillin binding assays indicated that CRO resistance was mainly associated with mutations in pbpA; mutations in ftsI also led to increased resistance to AMX. Knocking out cmeB and cmeD, which encode resistance

2017 Antimicrobial Agents and Chemotherapy

142. <i>Mycobacterium abscessus</i> L,D-transpeptidases are susceptible to inactivation by carbapenems and cephalosporins but not penicillins. Full Text available with Trip Pro

Mycobacterium abscessus L,D-transpeptidases are susceptible to inactivation by carbapenems and cephalosporins but not penicillins. As a growing number of clinical isolates of Mycobacterium abscessus are resistant to most antibiotics, new treatment options that are effective against these drug-resistant strains are desperately needed. The majority of the linkages in the cell wall peptidoglycan of M. abscessus are synthesized by nonclassical transpeptidases, namely, the l,d-transpeptidases (...) . Emerging evidence suggests that these enzymes represent a new molecular vulnerability in this pathogen. Recent studies have demonstrated that inhibition of these enzymes by the carbapenem class of β-lactams determines their activity against Mycobacterium tuberculosis Here, we studied the interactions of β-lactams with two l,d-transpeptidases in M. abscessus, namely, LdtMab1 and LdtMab2, and found that both the carbapenem and cephalosporin, but not penicillin, subclasses of β-lactams inhibit

2017 Antimicrobial Agents and Chemotherapy

143. A clinical decision-making algorithm for penicillin allergy. (Abstract)

A clinical decision-making algorithm for penicillin allergy. About 10% of subjects report suspected penicillin allergy, but 85-90% of these patients are not truly allergic and could safely receive beta-lactam antibiotics Objective: To design and validate a clinical decision-making algorithm, based on anamnesis (chronology, severity, and duration of the suspected allergic reactions) and reaching a 100% sensitivity and negative predictive value, to assess allergy risk related to a penicillin (...) prescription in general practise.All patients were included prospectively and explorated based on ENDA/EAACI recommendations. Results of penicillin allergy work-up (gold standard) were compared with results of the algorithm.Allergological work-up diagnosed penicillin hypersensitivity in 41/259 patients (15.8%) [95% CI: 11.5-20.3]. Three of these patients were diagnosed as having immediate-type hypersensitivity to penicillin, but had been misdiagnosed as low risk patients using the clinical algorithm. Thus

2017 Annals of Medicine

144. Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia. Full Text available with Trip Pro

Clonal Expansion of New Penicillin-Resistant Clade of Neisseria meningitidis Serogroup W Clonal Complex 11, Australia. In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease.

2017 Emerging Infectious Diseases

145. Meningococcal B Vaccine Failure With a Penicillin-Resistant Strain in a Young Adult on Long-Term Eculizumab. Full Text available with Trip Pro

Meningococcal B Vaccine Failure With a Penicillin-Resistant Strain in a Young Adult on Long-Term Eculizumab. We describe a case of invasive meningococcal disease due to a vaccine-preventable and penicillin-resistant strain in a fully immunized young adult on long-term complement inhibitor therapy and daily penicillin chemoprophylaxis. Eculizumab is a humanized monoclonal antibody that binds human complement C5 protein and inhibits the terminal complement pathway. It is currently recommended (...) for the treatment of complement-mediated thrombotic microangiopathies. An unwanted complication of inhibiting complement, however, is an increased risk of invasive meningococcal disease. Here, we report the first case of meningococcal group B vaccine failure in a young adult receiving eculizumab for atypical hemolytic uremic syndrome. She developed invasive meningococcal disease due to a vaccine-preventable and penicillin-resistant meningococcal group B strain 4 months after receiving 2 doses of meningococcal

2017 Pediatrics

146. Utility of minor determinants for skin testing in inpatient penicillin allergy evaluation. (Abstract)

Utility of minor determinants for skin testing in inpatient penicillin allergy evaluation. Most patients with a history of penicillin allergy can tolerate penicillin. Skin testing can identify tolerant patients, but not all known allergenic determinants are commercially available. Protocols exist that use only available reagents, but the sensitivity and safety of these protocols, particularly for hospitalized patients, are controversial.To determine the number of hospitalized patients referred (...) for penicillin skin testing who showed unique positivity to the minor determinants penicilloate and penilloate.A retrospective chart review was conducted of all inpatients who underwent penicillin skin testing at 1 institution. Patients were referred by their treating physician. All patients underwent skin prick testing to benzylpenicilloyl polylysine (major determinant), penicillin G, penicilloate, penilloate (minor determinants), amoxicillin, and positive and negative controls. If the result was negative

2017 Asthma & Immunology

147. Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews. Full Text available with Trip Pro

Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews. Benzathine penicillin G (BPG) is the only recommended treatment to prevent mother-to-child transmission of syphilis. Due to recent reports of country-level shortages of BPG, an evaluation was undertaken to quantify countries that have experienced shortages in the past 2 years and to describe factors contributing

2017 PLoS medicine

148. Development of a novel multi-penicillin assay and assessment of the impact of analyte degradation: lessons for scavenged sampling in antimicrobial pharmacokinetic study design. Full Text available with Trip Pro

Development of a novel multi-penicillin assay and assessment of the impact of analyte degradation: lessons for scavenged sampling in antimicrobial pharmacokinetic study design. Penicillins are widely used to treat infections in children; however, the evidence is continuing to evolve in defining the optimal dosing. Modern pediatric pharmacokinetic study protocols frequently favor opportunistic, "scavenged" sampling. This study aimed to develop a small-volume single assay for five major (...) penicillins and to assess the influence of sample degradation on inferences made using pharmacokinetic modeling, to investigate the suitability of scavenged sampling strategies. Using a rapid ultrahigh-performance liquid chromatographic-tandem mass spectrometric method, an assay for five penicillins (amoxicillin, ampicillin, benzylpenicillin, piperacillin, and flucloxacillin) in blood plasma was developed and validated. Penicillin stabilities were evaluated under different conditions. Using these data

2017 Antimicrobial Agents and Chemotherapy

149. Phylogenetic distribution and expression of a penicillin-binding protein homologue, Ear and its significance in virulence of Staphylococcus aureus. Full Text available with Trip Pro

Phylogenetic distribution and expression of a penicillin-binding protein homologue, Ear and its significance in virulence of Staphylococcus aureus. Staphylococcus aureus is an opportunistic human pathogen that can cause serious infections in humans. A plethora of known and putative virulence factors are produced by staphylococci that collectively orchestrate pathogenesis. Ear protein (Escherichia coli ampicillin resistance) in S. aureus is an exoprotein in COL strain, predicted

2017 Journal of Medical Microbiology

150. Enhancing antibiotic stewardship by tackling 'spurious' penicillin allergy. (Abstract)

Enhancing antibiotic stewardship by tackling 'spurious' penicillin allergy. Approximately 90-99% of patients with a label of penicillin allergy (PenA) are not allergic when comprehensively investigated. An inaccurate label of PenA has major public health implications-longer hospital stay, more frequent hospital admissions, greater use of fluoroquinolones, glycopeptides, cephalosporins and other expensive antibiotics resulting in significantly higher costs to the health service and predisposing

2017 Clinical and Experimental Allergy

151. A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as Treatment Agents for Early Syphilis in Jiangsu, China. Full Text available with Trip Pro

A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as Treatment Agents for Early Syphilis in Jiangsu, China. The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early syphilis because there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an human immunodeficiency virus coinfection.A randomized, open-label controlled study

2017 Clinical Infectious Diseases Controlled trial quality: uncertain

152. Impact of Penicillin Allergy on Empirical Carbapenem Use in Gram-Negative Bloodstream Infections: An Antimicrobial Stewardship Opportunity. (Abstract)

Impact of Penicillin Allergy on Empirical Carbapenem Use in Gram-Negative Bloodstream Infections: An Antimicrobial Stewardship Opportunity. Retrospective matched-cohort study evaluating association between penicillin allergy and empirical carbapenem use in gram-negative bloodstream infections (BSIs) and utility of antimicrobial stewardship interventions in reducing carbapenem utilization.Hospitalized adults with community-onset gram-negative BSI from January 1, 2010, to June 30, 2015, at two (...) large community hospitals in Columbia, SC, were identified. Antimicrobial stewardship interventions targeting penicillin allergy and carbapenem utilization were fully implemented January 1, 2014. Multivariate logistic regression was used to examine impact of penicillin allergy and antimicrobial stewardship interventions on empirical carbapenem use. Kaplan-Meier analysis was used to evaluate time to carbapenem deescalation in patients with penicillin allergy before and after interventions.Patients

2017 Pharmacotherapy

153. Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a narrative review. Full Text available with Trip Pro

Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a narrative review. Anti-staphylococcal penicillins (ASPs) are recommended as first-line agents in methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Concerns about their safety profile have contributed to the increased use of cefazolin. The comparative clinical effectiveness and safety profile of cefazolin versus ASPs for such infections remain unclear

2017 Clinical Microbiology and Infection

154. Benzathine Penicillin G once-every-3-week prophylaxis for recurrent erysipelas a retrospective study of 132 patients. (Abstract)

Benzathine Penicillin G once-every-3-week prophylaxis for recurrent erysipelas a retrospective study of 132 patients. To evaluate effectivity, safety and patients' adherence to benzathine penicillin G (BPG) 1,200,000 units (1.2 MU) once-every-3-week intramuscularly prophylaxis for recurrent erysipelas.Patients with documented two or more erysipelas episodes in last two years who received at least one of 10 planned doses of BPG 1.2 MU intramuscularly between January 2009 and December 2015 were (...) ; 95% CI: 0.05-0.34; p < .01). In univariate analysis recurrence was significantly associated only with presence of any local risk factor concurrently with obesity (OR 3.40; 95% CI: 1.10-10.50; p < .05).Benzathine penicillin G 1.2 MU once every 3 weeks is an effective and well-tolerated prophylaxis of recurrent erysipelas with good patient adherence to the treatment. Further studies to determine the appropriate duration of prophylaxis are necessary.

2017 Journal of Dermatological Treatment

155. Removal of Penicillin G by combination of sonolysis and Photocatalytic (sonophotocatalytic) process from aqueous solution: process optimization using RSM (Response Surface Methodology) Full Text available with Trip Pro

Removal of Penicillin G by combination of sonolysis and Photocatalytic (sonophotocatalytic) process from aqueous solution: process optimization using RSM (Response Surface Methodology) Penicillin G (PG) is used in a variety of infectious diseases, extensively. Generally, when antibiotics are introduced into the food chain, they pose a threat to the environment and can risk health outcomes. The aim of the present study was the removal of Penicillin G from an aqueous solution through (...) an integrated system of UV/ZnO and UV/WO3 with Ultrasound pretreatment.In this descriptive-analytical work dealing with the removal of Penicillin G from an aqueous solution, four significant variables, contact time (60-120 min), Penicillin G concentration (50-150 mg/L), ZnO dose (200-400 mg/L), and WO3 dose (100-200 mg/L) were investigated. Experiments were performed in a Pyrex reactor (batch, 1 Lit) with an artificial UV 100-Watt medium pressure mercury lamp, coupled with ultrasound (100 W, 40 KHz) for PG

2016 Electronic physician

156. Conformational dynamics in penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus, allosteric communication network and enablement of catalysis Full Text available with Trip Pro

Conformational dynamics in penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus, allosteric communication network and enablement of catalysis The mechanism of the β-lactam antibacterials is the functionally irreversible acylation of the enzymes that catalyze the cross-linking steps in the biosynthesis of their peptidoglycan cell wall. The Gram-positive pathogen Staphylococcus aureus uses one primary resistance mechanism. An enzyme, called penicillin-binding protein 2a

2017 Journal of the American Chemical Society

157. Suppression and Synthetic-Lethal Genetic Relationships of ΔgpsB Mutations Indicate That GpsB Mediates Protein Phosphorylation and Penicillin-Binding Protein Interactions in Streptococcus pneumoniae D39 Full Text available with Trip Pro

Suppression and Synthetic-Lethal Genetic Relationships of ΔgpsB Mutations Indicate That GpsB Mediates Protein Phosphorylation and Penicillin-Binding Protein Interactions in Streptococcus pneumoniae D39 GpsB regulatory protein and StkP protein kinase have been proposed as molecular switches that balance septal and peripheral (side-wall like) peptidoglycan (PG) synthesis in Streptococcus pneumoniae (pneumococcus); yet, mechanisms of this switching remain unknown. We report that ΔdivIVA mutations

2017 Molecular microbiology

158. Alanine-501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness Full Text available with Trip Pro

Alanine-501 Mutations in Penicillin-Binding Protein 2 from Neisseria gonorrhoeae: Structure, Mechanism, and Effects on Cephalosporin Resistance and Biological Fitness Resistance of Neisseria gonorrhoeae to expanded-spectrum cephalosporins such as ceftriaxone and cefixime has increased markedly in the past decade. The primary cephalosporin resistance determinant is a mutated penA gene, which encodes the essential peptidoglycan transpeptidase, penicillin-binding protein 2 (PBP2). Decreased (...) -spectrum cephalosporins, we randomized codon 501 in a mosaic penA allele and transformed N. gonorrhoeae to increased cefixime resistance. Interestingly, only five substitutions of Ala501 (A501V, A501T, A501P, A501R, and A501S) that increased resistance and preserved essential transpeptidase function were isolated. To understand their structural implications, these mutations were introduced into the nonmosaic PBP2-6140CT, which contains four C-terminal mutations present in PBP2 from the penicillin

2017 Biochemistry

159. Penicillin-Susceptible, Oxidase-Negative, Nonhemolytic, Nonmotile Bacillus megaterium in Disguise of Bacillus anthracis Full Text available with Trip Pro

Penicillin-Susceptible, Oxidase-Negative, Nonhemolytic, Nonmotile Bacillus megaterium in Disguise of Bacillus anthracis Bacillus anthracis is a bacterial pathogen of major concern. The spores of this bacteria can survive harsh environmental conditions for extended periods and are well recognized as a potential bioterror weapon with significant implications. Accurate and timely identification of this Bacillus species in the diagnostic laboratory is essential for disease and public health

2017 Case reports in infectious diseases

160. Interplay between Penicillin-binding proteins and SEDS proteins promotes bacterial cell wall synthesis Full Text available with Trip Pro

Interplay between Penicillin-binding proteins and SEDS proteins promotes bacterial cell wall synthesis Bacteria utilize specialized multi-protein machineries to synthesize the essential peptidoglycan (PG) cell wall during growth and division. The divisome controls septal PG synthesis and separation of daughter cells. In E. coli, the lipid II transporter candidate FtsW is thought to work in concert with the PG synthases penicillin-binding proteins PBP3 and PBP1b. Yet, the exact molecular

2017 Scientific reports

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