Evaluation of Oral Amoxicillin/Clavulanate for Urinary Tract Infections Caused by Ceftriaxone Non-Susceptible Enterobacterales.

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

Cefazolin vs Second-line Antibiotics for Surgical Site Infection Prevention After Total Joint Arthroplasty Among Patients With a Beta-lactam Allergy.

Background: Cefazolin is a first-line agent for prevention of surgical site infections (SSIs) after total joint arthroplasty. Patients labeled allergic to beta-lactam antibiotics frequently receive clindamycin or vancomycin perioperatively due to the perceived risk of a hypersensitivity reaction after exposure to cefazolin. Methods: This single-system retrospective review included patients labeled allergic to penicillin or cephalosporin antibiotics who underwent a primary total hip and/or knee arthroplasty between January 2020 and July 2021. A detailed chart review was performed to compare the frequency of SSI within 90 days of surgery and interoperative hypersensitivity reactions (HSRs) between patients receiving cefazolin and patients receiving clindamycin and/or vancomycin. Results: A total of 1128 hip and/or knee arthroplasties from 1047 patients were included in the analysis (cefazolin n = 809, clindamycin/vancomycin n = 319). More patients in the clindamycin and/or vancomycin group had a history of cephalosporin allergy and allergic reactions with immediate symptoms. There were fewer SSIs in the cefazolin group compared with the clindamycin and/or vancomycin group (0.9% vs 3.8%; P < .001) including fewer prosthetic joint infections (0.1% vs 1.9%). The frequency of interoperative HSRs was not different between groups (cefazolin = 0.2% vs clindamycin/vancomycin = 1.3%; P = .06). Conclusions: The use of cefazolin as a perioperative antibiotic for infection prophylaxis in total joint arthroplasty in patients labeled beta-lactam allergic is associated with decreased postoperative SSI without an increase in interoperative HSR.

Penicillin-allergy delabelling resources for clinicians practicing in resource-limited settings: a full educational resource review of the grey literature.

Background: The clinical and financial consequences associated with a penicillin-allergy label are increasingly evident and have garnered support from international organizations to prioritize penicillin-allergy delabelling programmes. Most settings lack access to resources including drug allergy specialists and rely on general practitioners (GPs) and pharmacists. Objectives: The aim of this scoping review was to identify and describe freely available penicillin-allergy delabelling materials to guide clinicians practising in resource-limited settings with initiative application. Methods: This scoping review searched two grey literature databases, six targeted websites and consulted content experts to identify freely available materials in the English language that provided evidence-based and actionable penicillin-allergy delabelling strategies. Study investigators ranked and voted on which screened resources should be included in the final review. Characteristics of resources were evaluated and compared. Results: Out of 1191 total citations, 6 open-access resources were included. Penicillin-allergy toolkits featuring various delabelling strategies were identified in four resources. The toolkits supported a broad range of downloadable and adaptable materials, predominantly targeted towards GPs. Patient educational materials were also provided. Another resource highlighted a point-of-care penicillin-allergy risk assessment calculator via a free mobile app that quickly and accurately identified low-risk penicillin-allergic patients. The final resource, a supplemental instructional video, presented impactful and standardized delabelling strategies that clinicians can adopt into daily practices. Conclusions: Limited penicillin-allergy delabelling materials are available in the grey literature but existing resources provide broad and diverse opportunities. Additional support from health protection agencies is critical to augment ongoing delabelling efforts.

Cost-Effectiveness Analysis of New Beta-Lactam Beta-Lactamase Inhibitor Antibiotics Versus Colistin for the Treatment of Carbapenem-Resistant Infections.

Introduction: Carbapenem-resistant organisms (CROs) present a serious public health problem. Limited treatment options has led to increased use of colistin and polymyxin. Since 2014, the US Food and Drug Administration approved 4 new beta-lactam beta-lactamase inhibitor (BLBLI) combination antibiotics with activity against CROs. These new antibiotics have been shown to be more effective and less toxic than colistin and polymyxin but are considerably more expensive. This study evaluated the cost-effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Methods: A decision-tree microsimulation model was used to evaluate the cost effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Treatment groups differed in risk of mortality and risk of an acute kidney injury (AKI). The relative risk of mortality was determined by creating a meta-analysis comparing new BLBLIs to colistin. Cost inputs included medication costs and the cost to treat an AKI. The primary outcomes include quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Model inputs included: clinical outcomes and adverse events (30-day mortality and AKI); cost of treatment and adverse drug events; and health utilities. A 3% discount was applied for outcomes. A lifetime horizon was used from the perspective of the US healthcare system with a willingness-to-pay (WTP) threshold of $100 000. A sensitivity analysis was done to incorporate uncertainty. Results: The meta-analysis found the treatment with a new BLBLI was associated with a 50% decrease in the relative risk of 30-day mortality compared to colistin (RR 0.47, 95% CI 0.25-0.88). Treatment with a new BLBLI cost $16 200 and produced 11.5 QALYs, on average. The average colistin based regimen cost $3500 and produced 8.3 QALYs. The new BLBLIs were determined to be cost-effective with an ICER of $3900 per QALY gained. Treatment with a BLBLI remained cost-effective under all uncertainty scenarios tested. Conclusion: New BLBLIs are cost-effective compared to colistin for the treatment of CROs and are associated with improved mortality and fewer AKI events. The use of colistin should be reserved for cases where new BLBLIs are not available or there is documented resistance to these new antibiotics.

Allowable room temperature excursions for refrigerated medications: A 20-year review.

PURPOSE: The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions while maintaining stability and potency. METHODS: During a 12-month period ending in June 2021, the prescribing information and published monographs from multiple pharmacy compendia were reviewed for all medications and biologic products approved by the US Food and Drug Administration (FDA) for human use since January 2000. Products that were subsequently withdrawn from the US market were excluded. When temperature excursion data was unavailable in published form, product manufacturers were surveyed via telephone and/or email. Acceptable storage information for all products for which storage is recommended at temperatures below room temperature (20-25 °C [68-77 °F]) was compiled and arranged in tabular format. RESULTS: Of the 705 products or formulations approved by FDA during the predefined time period, 246 were identified as requiring storage at temperatures below room temperature. After review of available prescribing information and manufacturer communications, if applicable, acceptable periods of excursion to temperatures at room temperature or higher were identified for 214 products (87%). CONCLUSION: Information related to acceptable periods of room temperature excursion was compiled for a total of 214 products approved for US distribution since 2000. The included tables may increase patient safety and decrease medication loss or related expenditures.

Immediate Hypersensitivity to Fluoroquinolones: A Cohort Assessing Cross-Reactivity.

Background: Fluoroquinolones are the second-most prescribed antimicrobial and are frequently associated with causing hypersensitivity reactions. Existing evidence regarding cross-reactivity of fluoroquinolones is limited, offering clinicians little guidance in understanding the implications of selecting an in-class alternative among patients with histories of allergic reactions to fluoroquinolones. The aim of this study was to compare the frequency of immediate hypersensitivity reactions to ciprofloxacin, levofloxacin, and/or moxifloxacin among patients with a history of immediate hypersensitivity to a different fluoroquinolone. Methods: This retrospective chart review included adult patients with a history of an immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin and a documented prescription for a different fluoroquinolone. The primary outcome was documentation of a hypersensitivity reaction upon second fluoroquinolone exposure. Results: A total of 321 cases met inclusion criteria. Of these cases, 2.5% experienced an immediate hypersensitivity reaction after second fluoroquinolone exposure to ciprofloxacin, levofloxacin, and/or moxifloxacin. Within the ciprofloxacin, levofloxacin, and moxifloxacin index allergy cohorts, the frequency of cross-reactivity was 2.5%, 2.0%, and 5.3%, respectively. Conclusions: Our data suggest that patients with a history of immediate hypersensitivity reaction to ciprofloxacin, levofloxacin, and/or moxifloxacin are at low risk of experiencing a cross-reaction when exposed to a different fluoroquinolone. Avoidance of all fluoroquinolones in this patient population may not be warranted.

Comparison of immediate hypersensitivity reactions to preoperative antibiotics in patients labeled as penicillin allergic.

BACKGROUND: Cefazolin is routinely recommended as the first-line agent for surgical antibiotic prophylaxis because it prevents more surgical site infections than second-line antibiotics. Clinicians often avoid administering cefazolin to patients who are labeled as penicillin allergic due to concerns of cross-reactivity. The aim of this study was to compare the incidence of hypersensitivity reactions between cefazolin and the second-line antibiotics vancomycin and clindamycin. METHODS: This retrospective study included patients who were labeled as penicillin allergic and received either cefazolin, clindamycin, or vancomycin as preoperative antibiotics. The primary outcome was intraoperative hypersensitivity reactions. RESULTS: A total of 734 surgical procedures in 690 patients were included. Fifteen immediate hypersensitivity reactions were identified. Probable hypersensitivity reactions occurred in 3 (0.9%) patients in the cefazolin group, 4 (1.4%) in the clindamycin group, and 1 (1.1%) in the vancomycin group. Seven of 8 patients reported allergies to additional medications beyond penicillin. There were seven cases of possible hypersensitivity reactions, 3 (0.9%) in the cefazolin group, 1 (1.1%) in the vancomycin group, and 3 (1.0%) in the clindamycin group. CONCLUSION: Our data suggest that perioperative hypersensitivity reactions are uncommon in patients labeled as penicillin allergic. The frequency of immediate hypersensitivity reactions was not different between patients receiving cefazolin, clindamycin, or vancomycin. Avoiding cefazolin in patients labeled as penicillin allergic may not be warranted.

Assessment of the Frequency of Dual Allergy to Penicillins and Cefazolin: A Systematic Review and Meta-analysis.

Importance: Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections. Objective: To examine the incidence of dual allergy to cefazolin and natural penicillins. Data Sources: MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020. Study Selection: In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion. Data Extraction and Synthesis: Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions. Main Outcomes and Measures: Dual allergy to cefazolin and a natural penicillin. Results: Seventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%; I2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%; I2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%; I2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%; I2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%; I2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%; I2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%; I2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin. Conclusions and Relevance: These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.

A Comprehensive Survey of Infectious Diseases Curriculum Among US Pharmacy Schools.

Objective. To describe what and how infectious diseases (ID) topics are taught in US schools of pharmacy and summarize pharmacy faculty members' and students' perceived successes and challenges in teaching and learning about ID. Methods. A 23-item survey instrument was distributed electronically to ID faculty members at 137 US pharmacy schools. Data collected included curricular hours and format, topics covered, active-learning strategies, and curricular successes and concerns. Results. Surveys were collected from 106 schools (77% response rate). Infectious diseases curricula were allotted a median of 60 (IQR=40) hours of classroom time. Respondents dedicated 33% of curriculum hours to ID fundamentals and 66% to disease states. Greater than 94% of schools taught all tier one ID topics from the 2016 American College of Clinical Pharmacy Pharmacotherapy Didactic Curriculum Toolkit. Curricula were primarily delivered through traditional lectures rather than active learning (75% vs 25% of classroom time, respectively). The median number of active-learning strategies used was four (IQR=3). The most common active-learning modalities used either consistently or frequently were patient case application (98%) and audience response systems (76%). The most common successes cited by faculty members were implementation of active learning, the "real-world" applicability of the ID topics, and the breadth of topics and topic exposure covered in the curriculum. The most common concerns were a lack of time to cover material and the amount of material covered. Conclusion. Increased communication and collaboration between ID educators is warranted to increase consistency of ID education and distribution of educational innovations.

Transition to Oral versus Continued Intravenous Antibiotics for Patients with Pyogenic Liver Abscesses: A Retrospective Analysis.

INTRODUCTION: The management of pyogenic liver abscesses usually requires 4 weeks of antibiotic therapy. It is unknown if oral (PO) antibiotics are as effective as intravenous (IV) antibiotics for this indication. OBJECTIVES: To compare 30-, 60-, and 90-day readmission rates between patients with pyogenic liver abscesses receiving IV antibiotics for the duration of therapy and those who were transitioned to PO antibiotics after discharge from the hospital. METHODS: This retrospective study included patients with pyogenic liver abscesses who had undergone percutaneous drainage and received IV antibiotics while in the hospital. Patients were grouped based on receipt of either PO or IV antibiotics at discharge. RESULTS: The final cohort resulted in 99 patients, 48 in the PO group and 51 in the IV group. The most common organisms identified were Klebsiella sp, Escherichia coli, and Streptococcus sp. The most common antibiotic received at discharge in the IV group was ertapenem or ceftriaxone plus metronidazole. Patients in the PO group most commonly received levofloxacin plus metronidazole at discharge. Thirty-day readmission occurred more frequently in the PO group (PO 39.6% vs IV 17.6%, p=0.03). The most common reasons for readmission were complications related to abscess or antibiotic. Univariate logistic regression for readmission identified PO antibiotics at discharge as an independent predictor of readmission at 30 days (odds ratio [OR] 3.1), 60 days (OR 3.9), and 90 days (OR 3.1). CONCLUSION: Transition to PO antibiotics that consisted mostly of fluoroquinolones for patients with pyogenic liver abscesses was associated with a higher rate of 30-day readmission compared with patients treated with IV antibiotics that consisted mostly of ß-lactams.

Comprehensive Assessment of Didactic Curriculum and Career Interest in Infectious Diseases Among Graduating United States Pharmacy Students.

BACKGROUND: The growing need for clinicians with antimicrobial stewardship (AS) skills has resulted in an examination of educational methods for pharmacy and medical learners. This study explores characteristics associated with student assessment of didactic infectious diseases (ID) education quality and variables associated with a career interest in ID and/or AS. METHODS: Infectious diseases faculty from US pharmacy schools were sent a 15-question survey in September 2017. Faculty members e-mailed the survey link to graduating pharmacy students. RESULTS: Participants from 29 pharmacy schools, representing 21 states, resulted in 537 student responses. Quality of ID didactic education was rated as Very Good by 41%, Good by 40%, Acceptable by 14%, and Poor by 4% of participants. The mean number of faculty-provided learning resources differed by quality rating and was significantly associated with perceived educational needs. Infectious diseases was identified as a career interest by 29% of students. These students more frequently rated their ID didactic education as Very Good (52% vs 37%, P < .01) and were more likely to become interested in ID during or after it was taught in pharmacy school (39% vs 21%, P < .01). CONCLUSIONS: In this cohort of graduating pharmacy students, the perceived quality of didactic ID education was associated with a career interest in ID and/or AS. Factors associated with quality of education were quantity and quality of faculty-provided resources. Increasing the quality of the didactic ID curriculum has potential to increase interest in ID/AS careers among pharmacy students.

Antimicrobial stewardship education in US colleges and schools of pharmacy.

Background: Pharmacists are key members of antimicrobial stewardship (AS) teams. It is unknown if and how US colleges and schools of pharmacy incorporate AS into their Doctor of Pharmacy (PharmD) curricula. Methods: This study was a cross-sectional, multicentre, electronic survey distributed to infectious diseases faculty or department chairs of 137 accredited and candidate-status PharmD programmes. Results: One hundred and sixteen programmes participated, representing an 84.7% response rate. AS education was integrated into the required didactic, elective didactic and experiential education components of the curricula in 79 (68.1%), 43 (37.1%) and 97 (83.6%) PharmD programmes, respectively. The most common AS topics in required and elective didactic curricula were AS definitions, principles and purpose (98.7% and 86.0%) and the pharmacist's role in AS (93.7% and 83.7%). In the required and elective didactic curricula, lecture (93.7% and 86.0%) and case-based instruction (57.0% and 83.7%) were the most common instructional methods. For experiential education, the pharmacist's role in AS (96.9%), de-escalation of antimicrobials (96.9%) and antimicrobial dose optimization (95.9%) were the most common AS topics. PharmD programmes employing a faculty member who specializes in AS were more likely to offer AS experiential education than programmes without AS faculty (88.1% versus 71.9%, P = 0.049). Conclusions: Integration of AS education in US PharmD curricula is variable and there are considerable differences in the AS activities and topics delivered. PharmD programmes should attempt to expose students to AS education to prepare future pharmacists for AS practice. Efforts should be made to incorporate interprofessional collaboration into AS education.

Clinical pharmacy academic career transitions: Viewpoints from the field.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is a three-part commentary series that explores select challenges: 1) feedback, evaluation, and advancement; 2) understanding and balancing of distribution of effort; 3) learning how and when to say yes. Faculty, or those interested in pursuing a career in pharmacy academia, can refer to this commentary series as a reference. Schools of pharmacy may utilize this as a tool for new faculty members during orientation in order to ensure smooth integration into the academic environment.

Clinical pharmacy academic career transitions: Viewpoints from the fieldPart 1: Understanding feedback, evaluation, and advancement.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is a three-part commentary series that explores select challenges: 1) feedback, evaluation and advancement; 2) understanding and balancing of distribution of effort; 3) learning how and when to say yes. Faculty, or those interested in pursuing a career in pharmacy academia, can refer to this commentary series as a reference. Schools of pharmacy may utilize this as a tool for new faculty members during orientation in order to ensure smooth integration into the academic environment.

Clinical pharmacy academic career transitions: Viewpoints from the field Part 2: Understanding and balancing the distribution of effort.

INTRODUCTION: The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. The authors represent faculty members teaching within a large, state-funded, research-intensive School of Pharmacy located within a large academic health center. The authors have various backgrounds and represent individuals making transitions at various points in their careers (from residency into academia, from a non-academic environment into academia, and from one academic environment to another). COMMENTARY: This is Part 2 of a three-part commentary series that focuses on understanding and balancing the distribution of effort. Parts 1 and 3 of this commentary series explore feedback, evaluation and advancement; and learning when and how to say yes, respectively. While the entire series is intended to be read in continuity, faculty, or those interested in pursuing a career in pharmacy academia, can refer to Part 2 as a reference to aid in understanding and balancing the different components and the distribution of effort associated with a position in academic pharmacy, specifically. IMPLICATIONS: Schools of Pharmacy may utilize this as a tool for new faculty members during orientation in order to help ensure faculty success.

Clinical pharmacy academic career transitions: Viewpoints from the field part 3: Learning when and how to say yes.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is Part 3 of a three-part commentary series that focuses on when and how to say yes to the multitude of opportunities available to pharmacy practice faculty. Part 1 discusses feedback, evaluation, and advancement. Part 2 explains distribution of effort (DOE) and how to marry the different components of teaching, research, and service. While the entire series is intended to be read in continuity, faculty, or those interested in pursuing a career in pharmacy academia, can refer to Part 3 as a reference on how to screen opportunities within academia to maximize professional and personal growth and minimize career burnout. Schools of pharmacy may utilize this as a tool for new faculty members during orientation to help ensure faculty success.

Systematic review of professional liability when prescribing ß-lactams for patients with a known penicillin allergy.

OBJECTIVE: To describe medical negligence and malpractice cases in which a patient with a known penicillin allergy received a ß-lactam and experienced an adverse reaction related to the ß-lactam. DATA SOURCES: Lexis-Nexus, Westlaw, and Google Scholar were searched. STUDY SELECTIONS: Medical negligence and malpractice cases were eligible for inclusion if they met the following criteria: the plaintiff had a known penicillin allergy, received a ß-lactam, and experienced an adverse event. All United States federal and state cases were eligible. RESULTS: Twenty-seven unique cases met the inclusion criteria. Eighteen cases involved the receipt of a penicillin-based antibiotic; of these cases with a known legal outcome, the plaintiff (patient or representative) prevailed or settled in 3 cases and defendants (providers) prevailed in 7 cases. Seven cases involved the receipt of a cephalosporin; of these cases with a known legal outcome, the plaintiff settled with physicians before trial in 1 case and defendants prevailed in 3 cases. Two cases involved the receipt of a carbapenem. Defendants prevailed in one case and the legal outcome of the other case is unknown. In cases in which the defense successfully moved for summary judgment, judges cited a lack of scientific evidence demonstrating a cephalosporin or carbapenem was contraindicated for a patient with a penicillin allergy. CONCLUSION: The cases with published legal outcomes found limited professional liability for clinicians who prescribed cephalosporins or carbapenems to a patient with a known penicillin allergy. These results may decrease the litigation fears of practitioners and risk managers within health care systems.