Showing papers on "Penicillin published in 2018"
TL;DR: Patients with a reported penicillin allergy had a 50% increased odds of SSI, attributable to the receipt of second-line perioperative antibiotics.
Abstract: Background A reported penicillin allergy may compromise receipt of recommended antibiotic prophylaxis intended to prevent surgical site infections (SSIs). Most patients with a reported penicillin allergy are not allergic. We determined the impact of a reported penicillin allergy on the development of SSIs. Methods In this retrospective cohort study of Massachusetts General Hospital hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, and coronary artery bypass grafting patients from 2010 to 2014, we compared patients with and without a reported penicillin allergy. The primary outcome was an SSI, as defined by the Centers for Disease Control and Prevention's National Healthcare Safety Network. The secondary outcome was perioperative antibiotic use. Results Of 8385 patients who underwent 9004 procedures, 922 (11%) reported a penicillin allergy, and 241 (2.7%) had an SSI. In multivariable logistic regression, patients reporting a penicillin allergy had increased odds (adjusted odds ratio, 1.51; 95% confidence interval, 1.02-2.22) of SSI. Penicillin allergy reporters were administered less cefazolin (12% vs 92%; P < .001) and more clindamycin (49% vs 3%; P < .001), vancomycin (35% vs 3%; P < .001), and gentamicin (24% vs 3%; P < .001) compared with those without a reported penicillin allergy. The increased SSI risk was entirely mediated by the patients' receipt of an alternative perioperative antibiotic; between 112 and 124 patients with reported penicillin allergy would need allergy evaluation to prevent 1 SSI. Conclusions Patients with a reported penicillin allergy had a 50% increased odds of SSI, attributable to the receipt of second-line perioperative antibiotics. Clarification of penicillin allergies as part of routine preoperative care may decrease SSI risk.
272 citations
TL;DR: Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of β lactam alternative antibiotics.
Abstract: Objective To evaluate the relation between penicillin allergy and development of meticillin resistant Staphylococcus aureus (MRSA) and C difficile. Design Population based matched cohort study. Setting United Kingdom general practice (1995-2015). Participants 301 399 adults without previous MRSA or C difficile enrolled in the Health Improvement Network database: 64 141 had a penicillin allergy and 237 258 comparators matched on age, sex, and study entry time. Main outcome measures The primary outcome was risk of incident MRSA and C difficile. Secondary outcomes were use of β lactam antibiotics and β lactam alternative antibiotics. Results Among 64 141 adults with penicillin allergy and 237 258 matched comparators, 1365 developed MRSA (442 participants with penicillin allergy and 923 comparators) and 1688 developed C difficile (442 participants with penicillin allergy and 1246 comparators) during a mean 6.0 years of follow-up. Among patients with penicillin allergy the adjusted hazard ratio for MRSA was 1.69 (95% confidence interval 1.51 to 1.90) and for C difficile was 1.26 (1.12 to 1.40). The adjusted incidence rate ratios for antibiotic use among patients with penicillin allergy were 4.15 (95% confidence interval 4.12 to 4.17) for macrolides, 3.89 (3.66 to 4.12) for clindamycin, and 2.10 (2.08 to 2.13) for fluoroquinolones. Increased use of β lactam alternative antibiotics accounted for 55% of the increased risk of MRSA and 35% of the increased risk of C difficile. Conclusions Documented penicillin allergy was associated with an increased risk of MRSA and C difficile that was mediated by the increased use of β lactam alternative antibiotics. Systematically addressing penicillin allergies may be an important public health strategy to reduce the incidence of MRSA and C difficile among patients with a penicillin allergy label.
205 citations
TL;DR: It is concluded that there is ample evidence to allow the safe use of cephalosporins in patients with isolated confirmed penicillin or amoxicillin allergy, and the structural involvement of the R1 and R2 chemical side chains of the cep Halosporin causing IgE-mediated cross-reactivity with penicillins and other cep HALsporins is debated.
130 citations
TL;DR: It is shown that mastitis pathogens were susceptible to most antibiotics with exceptions of staphylococci tested against penicillin and streptococci against erythromycin or tetracycline and the high need to set additional clinical breakpoints for antibiotics frequently used to treat mastitis is highlighted.
70 citations
TL;DR: A comprehensive overview on what is known about macrolides resistance with an emphasis on the macrolide phosphotransferase and esterase enzymes is presented and how this information can assist in addressing resistance to macrolid antibiotics is explored.
Abstract: Since their discovery in the early 1950s, macrolide antibiotics have been used in both agriculture and medicine. Specifically, macrolides such as erythromycin and azithromycin have found use as substitutes for β-lactam antibiotics in patients with penicillin allergies. Given the extensive use of this class of antibiotics it is no surprise that resistance has spread among pathogenic bacteria. In these bacteria different mechanisms of resistance have been observed. Frequently observed are alterations in the target of macrolides, i.e., the ribosome, as well as upregulation of efflux pumps. However, drug modification is also increasingly observed. Two classes of enzymes have been implicated in macrolide detoxification: macrolide phosphotransferases and macrolide esterases. In this review, we present a comprehensive overview on what is known about macrolide resistance with an emphasis on the macrolide phosphotransferase and esterase enzymes. Furthermore, we explore how this information can assist in addressing resistance to macrolide antibiotics.
67 citations
TL;DR: Conventional predictors of allergy toPenicillin performed weakly and the authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of nonsevere penicillus allergy in children.
Abstract: Background Diagnostic guidelines for penicillin allergy in children recommend cumbersome protocols based partially on data from adults, which may be suboptimal for pediatric use. Objective To assess the accuracy of tools for diagnosis of penicillin allergy in children. Methods A prospective, multicenter study was conducted in children with reported adverse events related to penicillin, excluding severe reactions. All patients underwent a uniform diagnostic protocol that consisted of clinical history, skin tests, serum specific IgE (sIgE), and, regardless of these results, drug provocation tests (DPTs). Results A total of 732 children (mean age, 5.5 years; 51.2% males) completed the allergy workup, including DPTs. Amoxicillin triggered 96.9% of all reactions. None of the patients with an immediate index reaction (IR) developed a reaction on DPT. Penicillin allergy was confirmed in 35 children (4.8%): 6 immediate reactions (17%) and 29 nonimmediate reactions (83%) on the DPT. No severe reactions were recorded. The allergist diagnosis based on the clinical history was not associated with the DPT final outcome. In 30 of 33 allergic patients (91%), the results of all skin tests and sIgE tests were negative. A logistic regression model identified the following to be associated with penicillin allergy: a family history of drug allergy (odds ratio [OR], 3.03; 95% confidence interval [CI], 1.33-6.89; P = .008), an IR lasting more than 3 days vs 24 hours or less (OR, 8.96; 95% CI, 2.01-39.86; P = .004), and an IR treated with corticosteroids (OR, 2.68; 95% CI, 1.30-5.54; P = .007). Conclusion Conventional predictors of allergy to penicillin performed weakly. The authors propose straightforward penicillin provocation testing in controlled, experienced centers for the diagnosis of nonsevere penicillin allergy in children.
61 citations
TL;DR: By functional analysis of residues required for hydrolysis, Sun et al. reveal stringent sequence constraints for carbapenems, suggesting that specific combinations of NDM-1 inhibitors might help reducing resistance development.
Abstract: New Delhi metallo-β-lactamase-1 exhibits a broad substrate profile for hydrolysis of the penicillin, cephalosporin and 'last resort' carbapenems, and thus confers bacterial resistance to nearly all β-lactam antibiotics. Here we address whether the high catalytic efficiency for hydrolysis of these diverse substrates is reflected by similar sequence and structural requirements for catalysis, i.e., whether the same catalytic machinery is used to achieve hydrolysis of each class. Deep sequencing of randomized single codon mutation libraries that were selected for resistance to representative antibiotics reveal stringent sequence requirements for carbapenem versus penicillin or cephalosporin hydrolysis. Further, the residue positions required for hydrolysis of penicillins and cephalosporins are a subset of those required for carbapenem hydrolysis. Thus, while a common core of residues is used for catalysis of all substrates, carbapenem hydrolysis requires an additional set of residues to achieve catalytic efficiency comparable to that for penicillins and cephalosporins.
60 citations
TL;DR: A β-lactamase, a novel type of amidase, and the phenylacetic acid catabolon comprise a catabolic pathway, revealed by genomic and transcriptomic analysis, that enables multiple soil bacteria to use β- lactam antibiotics as a carbon source.
Abstract: The soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. While resistance genes are widely distributed in the soil, there is a dearth of knowledge concerning antibiotic catabolism. Here we describe a pathway for penicillin catabolism in four isolates. Genomic and transcriptomic sequencing revealed β-lactamase, amidase, and phenylacetic acid catabolon upregulation. Knocking out part of the phenylacetic acid catabolon or an apparent penicillin utilization operon (put) resulted in loss of penicillin catabolism in one isolate. A hydrolase from the put operon was found to degrade in vitro benzylpenicilloic acid, the β-lactamase penicillin product. To test the generality of this strategy, an Escherichia coli strain was engineered to co-express a β-lactamase and a penicillin amidase or the put operon, enabling it to grow using penicillin or benzylpenicilloic acid, respectively. Elucidation of additional pathways may allow bioremediation of antibiotic-contaminated soils and discovery of antibiotic-remodeling enzymes with industrial utility.
59 citations
TL;DR: The 5-day challenge is a safe and effective way to rule out nonimmediate amoxicillin allergy, and it ensures better compliance with future penicillin use.
58 citations
TL;DR: It is demonstrated the successful and safe implementation of a pilot oral penicillin challenge program for cancer patients with low-riskPenicillin allergies, increasing the use of penicillus and narrow-spectrum beta-lactams post-testing.
Abstract: Antibiotic allergies are reported by up to 1 in 4 cancer patients, almost 50% of which are considered low risk and precede the cancer diagnosis. We demonstrate the successful and safe implementation of a pilot oral penicillin challenge program for cancer patients with low-risk penicillin allergies, increasing the use of penicillin and narrow-spectrum beta-lactams post-testing.
54 citations
TL;DR: In this article, β-lactams have been consistently associated with the majority of drug-related adverse events and these adverse events are mild under proper dosing and judicious selection.
Abstract: Introduction: β-lactams have been consistently associated with the majority of drug-related adverse events. Generally, these are mild under proper dosing and judicious selection.Areas covered: Imme...
TL;DR: A clinical practice algorithm for the perioperative evaluation and management of patients reporting a history of penicillin allergy is presented, concluding that cephalosporins can be safely administered to a majority of such patients.
Abstract: Administration of preoperative antimicrobial prophylaxis, often with a cephalosporin, is the mainstay of surgical site infection prevention guidelines. Unfortunately, due to prevalent misconceptions, patients labeled as having a penicillin allergy often receive alternate and less-effective antibiotics, placing them at risk of a variety of adverse effects including increased morbidity and higher risk of surgical site infection. The perioperative physician should ascertain the nature of previous reactions to aid in determining the probability of the prevalence of a true allergy. Penicillin allergy testing may be performed but may not be feasible in the perioperative setting. Current evidence on the structural determinants of penicillin and cephalosporin allergies refutes the misconception of cross-reactivity between penicillins and cefazolin, and there is no clear evidence of an increased risk of anaphylaxis in cefazolin-naive, penicillin-allergic patients. A clinical practice algorithm for the perioperative evaluation and management of patients reporting a history of penicillin allergy is presented, concluding that cephalosporins can be safely administered to a majority of such patients.
TL;DR: Children with low-risk penicillin allergy symptoms whose test results were negative for penicillus allergy tolerated aPenicillin challenge without a severe allergic reaction developing and delabeling children changed prescription behavior and led to actual health care savings.
Abstract: BACKGROUND: Penicillin allergy is commonly reported in the pediatric emergency department. We previously performed 3-tier penicillin allergy testing on children with low-risk symptoms, and 100% tolerated a penicillin challenge without an allergic reaction. We hypothesized that no serious allergic reactions would occur after re-exposure to penicillin and that prescription practices would change after testing. METHODS: We performed a follow-up case series of 100 children whose test results were negative for penicillin allergy. Research staff administered a brief follow-up phone survey to the parent and primary care provider of each patient tested. We combined the survey data and summarized baseline patient characteristics and questionnaire responses. We then completed a 3-tier economic analysis from the prescription information gathered from surveys in which cost savings, cost avoidance, and potential cost savings were calculated. RESULTS: A total of 46 prescriptions in 36 patients were reported by the primary care provider and/or parents within the year after patients were tested for penicillin allergy. Twenty-six (58%) of the prescriptions filled were penicillin derivatives. One (4%) child developed a rash 24 hours after starting the medication; no child developed a serious adverse reaction after being given a penicillin challenge. We found that the cost savings of delabeling patients as penicillin allergic was $1368.13, the cost avoidance was $1812.00, and the total potential cost savings for the pediatric emergency department population was $192 223.00. CONCLUSIONS: Children with low-risk penicillin allergy symptoms whose test results were negative for penicillin allergy tolerated a penicillin challenge without a severe allergic reaction developing. Delabeling children changed prescription behavior and led to actual health care savings.
TL;DR: These findings provide evidence that S. aureus CRB has at least two P BP4-mediated resistance mechanisms, and present the first crystallographic PBP4 structures of apo and acyl-enzyme intermediate forms complexed with three late-generation β-lactam antibiotics: ceftobiprole, ceftaroline, and nafcillin.
TL;DR: In this article, the gamma radiation-induced degradation of penicillin G was inhibited in the presence of peptone and glucose and the inhibitive effect increased with increasing their concentrations.
TL;DR: Although IPD has decreased greatly and stabilized in the post-PCV13 era, the species continually generates recombinants that adapt to selective pressures exerted by vaccines and antimicrobials.
Abstract: Invasive pneumococcal disease (IPD) has greatly decreased since implementation in the U.S. of the 7 valent conjugate vaccine (PCV7) in 2000 and 13 valent conjugate vaccine (PCV13) in 2010. We used whole genome sequencing (WGS) to predict phenotypic traits (serotypes, antimicrobial phenotypes, and pilus determinants) and determine multilocus genotypes from 5334 isolates (~90% of cases) recovered during 2015-2016 through Active Bacterial Core surveillance. We identified 44 serotypes; 26 accounted for 98% of the isolates. PCV13 serotypes (inclusive of serotype 6C) accounted for 1503 (28.2%) isolates, with serotype 3 most common (657/5334, 12.3%), while serotypes 1 and 5 were undetected. Of 305 isolates from children 0.12 μg/ml) was found among 22.4% (1193/5334) isolates, with higher penicillin MICs (2-8 μg/ml) found in 8.0% (425/5334) of isolates that were primarily (372/425, 87.5%) serotypes 35B and 19A. Most (792/1193, 66.4%) penicillin-nonsusceptible isolates were macrolide-resistant, 410 (34.4%) of which were erm gene positive and clindamycin-resistant. The proportion of macrolide-resistant isolates increased with increasing penicillin MICs; even isolates with reduced penicillin susceptibility (MIC = 0.06 μg/ml) were much more likely to be macrolide-resistant than basally penicillin-susceptible isolates (MIC < 0.03 μg/ml). The contribution of recombination to strain diversification was assessed through quantitating 35B/CC558-specific bioinformatic pipeline features among non-CC558 CCs and determining the sizes of gene replacements. Although IPD has decreased greatly and stabilized in the post-PCV13 era, the species continually generates recombinants that adapt to selective pressures exerted by vaccines and antimicrobials. These data serve as a baseline for monitoring future changes within each invasive serotype.
TL;DR: The rates of ciprofloxacin resistance and penicillin resistance were very high across Germany, and the percentage of isolates with resistance to cefixime was low, whereas azithromycin resistance showed high levels during the observation period.
Abstract: The widespread antimicrobial resistance of Neisseria gonorrhoeae is a serious problem for the treatment and control of gonorrhoea Many of the previously effective therapeutic agents are no longer viable Because N gonorrhoeae infections are not reportable in Germany, only limited data on disease epidemiology and antimicrobial susceptibility patterns are available The Gonococcal Resistance Network (GORENET) is a surveillance project to monitor trends in the antimicrobial susceptibility of N gonorrhoeae in Germany in order to guide treatment algorithms and target future prevention strategies Between April 2014 and December 2015, data on patient-related information were collected from laboratories nationwide, and susceptibility testing was performed on 537 N gonorrhoeae isolates forwarded from the network laboratories to the Conciliar Laboratory for gonococci Susceptibility results for cefixime, ceftriaxone, azithromycin, ciprofloxacin and penicillin were defined according to EUCAST 40 standards Percentages, medians and interquartile ranges (IQR) were calculated Altogether, 90% of isolates were from men The median age was 32 (IQR 25–44) years for men and 25 (IQR 22–40) years for women (p-value < 0001) The most frequently tested materials among men were urethral (961%) and rectal swabs (17%), and among women, it was mainly endocervical and vaginal swabs (843%) None of the isolates were resistant to ceftriaxone Furthermore, 19% (in 2014) and 14% (in 2015) of the isolates were resistant to cefixime, 119% and 98% showed resistance against azithromycin, 720% and 583% were resistant to ciprofloxacin, and 291% and 188% were resistant to penicillin Resistance to ceftriaxone was not detected, and the percentage of isolates with resistance to cefixime was low, whereas azithromycin resistance showed high levels during the observation period The rates of ciprofloxacin resistance and penicillin resistance were very high across Germany Continued surveillance of antimicrobial drug susceptibilities for N gonorrhoeae remains highly important to ensure efficient disease management
TL;DR: Heat treatment can be considered as an effective pretreatment for PMD practical application and variations of germination index (GI) implied that the created phytotoxicity was significantly reduced.
TL;DR: The current PBPK model can help predict milk discard interval for penicillin following extralabel use through IM and IMM administrations and showed that even 4 times label dose did not lead to violative tissue residues in healthy dairy cows with IMM infusions.
TL;DR: Analysis of antibiotic susceptibility testing data for clinical Corynebacterium isolates received between 2011 and 2016 revealed that empirical drug treatment options are limited to vancomycin and linezolid, and much lower susceptibility to penicillin is shown than previously reported in the literature.
Abstract: Non-diphtheriae Corynebacterium-associated disease has been increasingly observed and often presents a conundrum to the treating physician. Analysis of antibiotic susceptibility testing data for 1,970 clinical Corynebacterium isolates received between 2011 and 2016 revealed that empirical drug treatment options are limited to vancomycin and linezolid. Corynebacterium striatum was the most frequently observed species during this study period, along with C. amycolatum and C. pseudodiphtheriticum/C. propinquum Low levels of susceptibility to penicillin (14.5%), erythromycin (15.1%), and clindamycin (8.7%) were observed for non-diphtheriae Corynebacterium species, while 3.0% of isolates were not susceptible to daptomycin. Similarly, 26.9% and 38.1% of Corynebacterium isolates were susceptible to ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. Our data show much lower susceptibility to penicillin than previously reported in the literature and an increasing number of isolates resistant to daptomycin, highlighting the need for continued antibiotic surveillance studies for appropriate patient management and treatment success.
TL;DR: The aim of this study was to evaluate the antimicrobial susceptibilities of 866 Neisseria meningitidis invasive strains during 11 years of surveillance in Italy and found that two and six strains were resistant to ciprofloxacin and rifampin, respectively.
Abstract: The aim of this study was to evaluate the antimicrobial susceptibilities of 866 Neisseria meningitidis invasive strains during 11 years of surveillance in Italy. Two and six strains were resistant to ciprofloxacin and rifampin, respectively. Forty-five percent were penicillin intermediate, associated with hypervirulent serogroup C clonal complex 11. All of the strains were susceptible to cephalosporins.
TL;DR: The tremendous advantages offered by β-lactam therapy are reviewed and a strong case is made that the debunking of false penicillin allergies through a detailed allergy history andPenicillin allergy testing should be a vital component of antimicrobial stewardship practices.
Abstract: The majority of patients with reported penicillin allergy are not allergic when tested or challenged. Penicillin allergy testing has been shown to significantly reduce annual healthcare expenditures. Data have emerged showing β-lactams have multidimensional antibacterial effects in vivo, far beyond what is appreciated in standard bacteriological susceptibility testing media. These include enhancing bacterial killing by the innate immune system. Supporting the clinical relevance of these secondary underappreciated effects are recent clinical and pharmacoeconomic analyses that show worse outcomes in patients with reported penicillin allergies who receive non-β-lactam antibiotics when compared to their non-penicillin-allergic counterparts. This is particularly relevant in the treatment of Staphylococcus aureus bacteremia. This article reviews the tremendous advantages offered by β-lactam therapy and makes a strong case that the debunking of false penicillin allergies through a detailed allergy history and penicillin allergy testing should be a vital component of antimicrobial stewardship practices.
TL;DR: A significant increase in the number of antibiotic-resistant bacteria was observed, which varied with different antibiotics, and the largest number of bacteria became resistant to nitrofurantoin and penicillin.
TL;DR: None of the MRSA isolates were sensitive to penicillin and ampicillin, however, low resistance was found for chloramphenicol and clindamycin, and being diabetic and use of hands rub was statistically significant with MRSA colonization.
Abstract: The aim of this study was to determine nasal carriage, risk factors and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus among health care-workers of Adigrat and Wukro hospitals Northern Ethiopia. The overall prevalence of S. aureus and methicillin resistance S. aureus (MRSA) in the present study were 12% (29/242) and 5.8% (14/242) respectively. The rate of MRSA among S. aureus was 48.3%(14/29). In this study, MRSA carriage was particularly higher among nurse professionals (7.8%) and surgical ward (17.1%). None of the MRSA isolates were sensitive to penicillin and ampicillin. However, low resistance was found for chloramphenicol and clindamycin. Being diabetic and use of hands rub was statistically significant with MRSA colonization.
TL;DR: Insight is provided into the status of antimicrobial resistance of staphylococci isolated from food and clinical samples in Algeria and the tetM/K, blaZ, aacA-aphD, ermC and mecA genes were detected in food andclinical isolates.
Abstract: The antimicrobial resistance of staphylococci rose worldwide. In total, 96 Staphylococcus isolates from food and clinical samples were collected from two provinces in Algeria. The antimicrobial susceptibility testing was performed and resistance-associated genes were detected. Fifty-one strains were isolated from food samples and differentiated into 33 Staphylococcus aureus and 18 coagulase-negative staphylococci. Forty-five staphylococci were collected from hospital and community-acquired infection cases. All S. aureus isolated from food were resistant to penicillin and 45.5% were resistant to tetracycline. The resistance rates of 45 clinical Staphylococcus isolates were 86.7%, 48.9%, 37.8% and 20.0% to penicillin, tetracycline, erythromycin and kanamycin, respectively. Nine isolates were confirmed as MRSA from food and clinical isolates. One S. aureus originated from food was confirmed as vancomycin-resistant. Multidrug-resistance was observed among 25.5% and 53.3% of food and clinical staphylococci, respectively. The tetM/K, blaZ, aacA-aphD, ermC and mecA genes were detected in food and clinical isolates. ermA gene was not found. This study provided insight into the status of antimicrobial resistance of staphylococci isolated from food and clinical samples in Algeria. Further investigations and surveillance programmes are mandatory.
TL;DR: The reduced susceptibility to β-lactam antibiotics observed in E. faecalis LS4828 results from a combination of both increased expression and remodeling of the active site, resulting in reduced affinity for penicillins and carbapenems.
Abstract: Enterococcus faecalis strains resistant to penicillin and ampicillin are rare and have been associated with increases in quantities of low-affinity penicillin-binding protein 4 (PBP4) or with amino acid substitutions in PBP4. We report an E. faecalis strain (LS4828) isolated from a prosthetic knee joint that was subjected to long-term exposure to aminopenicillins. Subsequent cultures yielded E. faecalis with MICs of penicillins and carbapenems higher than those for wild-type strain E. faecalis JH2-2. Sequence analysis of the pbp4 gene of LS4828 compared to that of JH2-2 revealed two point mutations with amino acid substitutions (V223I, A617T) and deletion of an adenine from the region upstream of the predicted pbp4 −35 promoter sequence (UP region). Purified PBP4 from LS4828 exhibited less affinity for Bocillin FL than did PBP4 from JH2-2, which was recapitulated by purified PBP4 containing only the A617T mutation. Differential scanning fluorimetry studies showed that the LS4828 and A617T variants are destabilized compared to wild-type PBP4. Further, reverse transcription-PCR indicated increased transcription of pbp4 in LS4828 and Western blot analysis with polyclonal PBP4 antibody revealed greater quantities of PBP4 in LS4828 than in JH2-2 lysates and membrane preparations. Placing the promoter regions from LS4828 or JH2-2 upstream of a green fluorescent protein reporter gene confirmed that the adenine deletion was associated with increased transcription. Together, these data suggest that the reduced susceptibility to β-lactam antibiotics observed in E. faecalis LS4828 results from a combination of both increased expression and remodeling of the active site, resulting in reduced affinity for penicillins and carbapenems. IMPORTANCEEnterococcus faecalis is an important cause of community-acquired and nosocomial infections and creates therapeutic dilemmas because of its frequent resistance to several classes of antibiotics. We report an E. faecalis strain with decreased ampicillin and imipenem susceptibility isolated after prolonged courses of aminopenicillin therapy for a prosthetic joint infection. Its reduced susceptibility is attributable to a combination of increased quantities of low-affinity PBP4 and an amino acid substitution in proximity to the active site that destabilizes the protein. Our findings provide a cautionary tale for clinicians who elect to “suppress” infections in prosthetic joints and offer novel insights into the interaction of β-lactam antibiotics with low-affinity PBP4. These insights will help inform future efforts to develop therapeutics capable of inhibiting clinical enterococcal strains.
TL;DR: High prevalence resistance to penicillin, tetracycline, and ciprofloxacin in N. gonorrhoeae obviates their use in future national treatment algorithms for genital discharge, and it is essential to continue monitoring for emerging resistance to currently recommended antimicrobial therapy in this rapidly evolving pathogen.
Abstract: Background: In South Africa, sexually transmitted infections (STIs) are managed through a syndromic approach at primary healthcare centres (PHCs). Neisseria gonorrhoeae is the predominant cause of male urethritis syndrome. We describe antimicrobial resistance patterns and trends in Neisseria gonorrhoeae during a ten-year surveillance period at a large PHC in Johannesburg. Methods: Neisseria gonorrhoeae was cultured from genital discharge swab specimens obtained from consenting adult patients presenting at the Alexandra Health Centre in Johannesburg between 2008 and 2017. Isolates were tested for antimicrobial susceptibility by Etest™ (cefixime, ceftriaxone, ciprofloxacin) or agar dilution (penicillin, tetracycline, azithromycin). Results: During the period of surveillance, high-level resistance prevalence increased from 30% to 51% for penicillin (p-value for trend < 0.001), 75% to 83% for tetracycline (p-value for trend = 0.008), and 25% to 69% for ciprofloxacin (p-value for trend < 0.001). Analysis did not reveal high-level resistance to spectinomycin or a minimum inhibitory concentration (MIC) creep for extended-spectrum cephalosporins, and the prevalence of intermediate-resistance to azithromycin was less than 5%. Conclusions: High prevalence resistance to penicillin, tetracycline, and ciprofloxacin in N. gonorrhoeae obviates their use in future national treatment algorithms for genital discharge. It is essential to continue monitoring for emerging resistance to currently recommended antimicrobial therapy in this rapidly evolving pathogen.
TL;DR: Targeting penicillin allergy testing to patients on aztreonam yields therapeutic and economic benefits during a single admission and provides a cost-effective model for inpatient testing.
Abstract: Background Patients reporting penicillin allergy often receive unnecessary and costly broad-spectrum alternatives such as aztreonam with negative consequences. Penicillin allergy testing improves antimicrobial therapy but is not broadly used in hospitals due to insufficient testing resources and short-term expenses. We describe a clinical decision support (CDS) tool promoting pharmacist-administered penicillin allergy testing in patients receiving aztreonam and its benefits toward antimicrobial stewardship and costs. Methods A CDS tool was incorporated into the electronic medical record, directing providers to order penicillin allergy testing for patients receiving aztreonam. An allergy-trained pharmacist reviewed orders placed through this new guideline and performed skin testing and oral challenges to determine whether these patients could safely take penicillin. Data on tests performed, antibiotic utilization, and cost-savings were compared with patients tested outside the new guideline as part of our institution's standard stewardship program. Results The guideline significantly increased penicillin allergy testing among patients receiving aztreonam from 24% to 85% (P < .001) while reducing the median delay between admission and testing completion from 3.31 to 1.05 days (P = 0.008). Patients tested under the guideline saw a 58% increase in penicillin exposure (P = .046). Institutional aztreonam administration declined from 2.54 to 1.47 administrations per 1000 patient-days (P = .016). Average antibiotic costs per patient tested before and after CDS decreased from $1265.81 to $592.08 USD, a 53% savings. Conclusions Targeting penicillin allergy testing to patients on aztreonam yields therapeutic and economic benefits during a single admission. This provides a cost-effective model for inpatient testing.
TL;DR: IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identifyPenicillin allergy history-positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis.
Abstract: Objective To review the history of the penicillin minor determinants and evaluate their relevance for current diagnosis. Data Sources Skin testing to detect immunoglobulin E (IgE) sensitivity to penicillins in patients with a history of penicillin allergy has been the subject of more than 55 years of published research involving tens of thousands of patients. Study Selections Selection of data was based on its relevance to the objective of this article. Results It was established early on that testing with the major penicilloyl determinant using the polyvalent penicilloyl-polylysine (PPL) is negative in a substantial portion (10% to 64%, including recent increases) of those at risk for immediate hypersensitivity reactions. A variety of minor penicillin determinants are clinically significant in that their use in skin testing is essential to detect all those at risk. In particular, a minor determinant mixture of benzylpenicillin, benzylpenicilloate, and benzylpenilloate, used in conjunction with PPL, has been shown in numerous studies to achieve an average negative predictive value (NPV) of 97.9% in history-positive patients. Benzylpenicillin alone, as the sole minor determinant, leaves many skin test–positive patients undiscovered. Use of amoxicillin as an additional minor determinant reagent appears to identify another 2% to 8% of skin test–positive patients in some populations. Conclusion IgE skin testing, using both the major and appropriate minor determinants of penicillin, can identify, with a high degree of reliability (NPV ∼97%), penicillin allergy history–positive patients who can receive beta-lactam antibiotics without concern for serious acute allergy, including anaphylaxis. The few false-negative skin tests reported globally are largely confined to minor, self-limited cutaneous reactions.
TL;DR: Clinicians and patients need to be supported to use PAT services and equipped with the skills to use penicillins appropriately following a negative allergy test result, and lack of awareness and knowledge of PAT services by both clinicians and patients is suggested.
Abstract: About 10% of U.K. patients believe that they are allergic to penicillin and have a "penicillin allergy label" in their primary care health record. However, around 90% of these patients may be mislabelled. Removing incorrect penicillin allergy labels can help to reduce unnecessary broad-spectrum antibiotic use. A rapid review was undertaken of papers exploring patient and/or clinician views and experiences of penicillin allergy testing (PAT) services and the influences on antibiotic prescribing behaviour in the context of penicillin allergy. We reviewed English-language publications published up to November 2017. Limited evidence on patients' experiences of PAT highlighted advantages to testing as well as a number of concerns. Clinicians reported uncertainty about referral criteria for PAT. Following PAT and a negative result, a number of clinicians and patients remained reluctant to prescribe and consume penicillins. This appeared to reflect a lack of confidence in the test result and fear of subsequent reactions to penicillins. The findings suggest lack of awareness and knowledge of PAT services by both clinicians and patients. In order to ensure correct penicillin allergy diagnosis, clinicians and patients need to be supported to use PAT services and equipped with the skills to use penicillins appropriately following a negative allergy test result.