Methicillin-Resistant Staphylococcus aureus Bacteremia Treated With Vancomycin Calculated by Area-Under-the-Curve in Patients With Elevated Vancomycin Minimum Inhibitory Concentrations.

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure.

Counting the Cost of Daptomycin Versus Vancomycin in Hospitalized Patients: A Cost Minimization Analysis.

Daptomycin use for gram-positive infections has increased. This cost minimization analysis aimed to determine cost and/or time savings of daptomycin over vancomycin. The estimated hospital cost savings was US$166.41 per patient, and pharmacist time saved of almost 20 minutes per patient. Daptomycin has the potential to save both time and money.

The prevalence of gram-negative bacteria with difficult-to-treat resistance and utilization of novel ß-lactam antibiotics in the southeastern United States.

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel ß-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU). Design: Retrospective, multicenter, cohort. Setting: Ten hospitals in the southeastern United States. Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel ß-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel ß-lactams. Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 (P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel ß-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden. Conclusions: The overall prevalence of GNB with DTR and the use of novel ß-lactams remain low. However, the uptrend in the use of novel ß-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR.

Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

INTRODUCTION: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. METHODS: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. RESULTS: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. CONCLUSIONS: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

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.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications for Hospitalized Patients in 2021.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an "actionable" intervention among hospitalized populations during 2021. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight "actionable" interventions used by antimicrobial stewardship programs in hospitalized populations to capture potentially effective strategies for local implementation.

Evaluation of Dalbavancin in Vancomycin Allergic Patients: A Case Series.

PURPOSE: There is a paucity of data regarding dalbavancin use in patients with a vancomycin allergy because of potential cross-reactivity between the 2 glycopeptide antibiotics. METHODS: A retrospective medical record review was performed between February 2016 and February 2021 in patients with a listed vancomycin allergy who received dalbavancin as an outpatient infusion and had a listed vancomycin allergy in the electronic health record. FINDINGS: There were 559 unique patients during the study period who received dalbavancin as an outpatient infusion, 10 of whom had a documented vancomycin allergy in the electronic health record. Four of the 10 patients had a history of a type I IgE-mediated reaction to vancomycin, 1 patient reported delayed rash, 2 patients reported a vancomycin infusion reaction, 2 patients reported acute kidney injury, and 1 patient reported intolerance with general malaise. All 10 patients received at least 1 dose of dalbavancin with no reported adverse events. IMPLICATIONS: This case series displays that all patients who received dalbavancin tolerated the infusion well with no adverse events reported. Dalbavancin may be a viable option for patients with a listed vancomycin allergy.

Rethinking residency recruitment, application, and interview processes to benefit applicants and programs long-term.

Pharmacy residency recruitment and interviews have been significantly impacted by the COVID-19 pandemic. Many traditional recruitment events and interviews were transitioned from in-person to virtual, and new approaches to recruitment, such as virtual open houses, were developed. There are limited data on how these changes impacted pharmacy residency applicants and programs, and the future of virtual events is currently unknown. We highlight recommendations for virtual recruitment and interviews and provide suggestions for residency programs and national organizations to improve virtual processes in the future.

Evaluation of Pharmacy Residency Recruitment and Interview Processes during the COVID-19 Pandemic (2020-2021 Application Cycle).

Introduction: Due to the COVID-19 pandemic, most pharmacy residency programs changed to an all-virtual format for recruitment and interviews for the 2020-2021 application cycle. There are no data evaluating the experiences and perceptions of these changes from the perspective of pharmacy residency programs and applicants. Methods: An electronic cross-sectional survey was distributed via email to post-graduate year 1 (PGY1) and post-graduate year 2 (PGY2) pharmacy residency programs and applicants across the Southeastern United States. Results have been reported according to the Checklist for Reporting of Survey Studies (CROSS) guidelines (Enhancing the QUAlity and Transparency Of health Research [EQUATOR] Network). Results: 142 residency applicants and 104 residency programs responded to the survey. Most respondents participated in virtual recruitment and interviews. In 2020-2021, less residency programs participated in local/regional showcases and personal placement services, but social media engagement increased. Of the applicants who responded, over half felt the need to apply to more programs during this application cycle, and a corresponding increase in applications were seen by residency programs. Residency interviews appeared shorter than previous years, and less programs offered an informal time to get to know the applicants. Overall, applicants and residency programs preferred on-site interviews, but both parties reported feeling confident creating rank lists after virtual interviews. Conclusion: These results highlight the impact of COVID-19 on residency recruitment and the interview process. Residency programs should implement feedback for improving the virtual experience, as able. The ongoing pandemic may affect the 2022-2023 application cycle, and pharmacy leadership organizations should consider developing guidance for applicants and residency programs on navigating another year of virtual events.This article is protected by copyright. All rights reserved.

A Continuing Education Activity Durably Addressed Knowledge Gaps Related to Penicillin Allergies Among Pharmacists and Pharmacy Technicians.

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

Real-world, multicentre evaluation of the incidence and risk factors for non-susceptible Stenotrophomonas maltophilia isolates.

BACKGROUND: Stenotrophomonas maltophilia is a cause of infection most commonly in the opportunistic host. Trimethoprim-sulfamethoxazole and levofloxacin are considered first-line treatment agents. With reports of increasing resistance to these first-line agents, it is important to determine risk factors associated with a non-susceptible isolate. METHODS: This was a real-world, multicentre, retrospective case-control study from five centres in the southeast United States evaluating S. maltophilia. The primary outcome was risk factors associated with non-susceptibility of S. maltophilia isolates to ≥1 antimicrobial agents. Secondary outcomes include incidence of S. maltophilia non-susceptibility, all-cause mortality, and 30-day readmission rates. RESULTS: There were 325 patients included in the study. For the primary outcome, the only factor associated with non-susceptibility per univariate analysis was isolation from urine culture (13.3% vs. 5.4%; P = 0.014), whereas the presence of mechanical ventilation (37.7% vs. 21.5%) and intensive care unit admission (35.3% vs. 18.4%) were associated with susceptibility (P < 0.001). For the secondary outcomes, non-susceptibility was present in 49% of isolates with 43 of 325 (13.2%), 53 of 324 (16.4%), and 105 of 172 (61%) to TMP-SMX, levofloxacin, and ceftazidime, respectively. Resistance to chloramphenicol and tigecycline was observed among 5/26 and 11/16 of tested isolates, respectively. Sixty-six patients (20%) experienced all-cause, inpatient mortality (18% susceptible vs. 23% non-susceptible; P = 0.280) and 44 patients (17%) were readmitted within 30 days of discharge (16% susceptible vs. 18% non-susceptible; P = 0.673). CONCLUSION: S. maltophilia non-susceptibility had a prevalence of ∼50% to at least one first-line or commonly used agent. More research is needed to delineate risk factors for non-susceptible isolates.

Influence of Probiotics on the Development of Clostridioides difficile Infection in Patients Receiving Fluoroquinolones.

Fluoroquinolones are associated with an increased risk of Clostridioides difficile infection (CDI). Probiotic supplementation has been shown to reduce the risk of antibiotic-associated diarrhea with variable effects on CDI. The objective of this study was to evaluate receipt of probiotics on development of primary CDI among hospitalized patients receiving fluoroquinolones. A retrospective cohort was evaluated that consisted of two groups of 100 patients each, admitted August 2018 through August 2020 that received ≥3 days of definitive monotherapy with levofloxacin or ciprofloxacin within 72 h of admission. Primary outcome was incidence of CDI. Secondary outcomes included rates of C. difficile diagnostic stool testing, additional infectious diagnostic testing, and non-CDI related gastrointestinal side effects. Patients on fluoroquinolones who received probiotics had a non-statistically significantly lower incidence in overall cases of CDI compared to those who did not receive probiotics (0% vs. 3%, p = 0.246). Patients who received probiotics had statistically significantly fewer C. difficile diagnostic stool tests performed (4% vs. 16%, p = 0.005) and fewer additional infectious diagnostic testing performed (4% vs. 10%, p = 0.096), respectively. Further research is warranted to optimize and standardize probiotic prescribing in high-risk patients.

Eosinophilic pneumonia caused by cefepime: A case report and review.

Eosinophilic pneumonia (EP) is characterized by accumulation of eosinophils in the lungs and has been associated with several medications, including antimicrobials. Cefepime is a commonly used broad-spectrum antimicrobial agent for the treatment of nosocomial infections but to date has not been associated with EP. We report the first documented case of EP secondary to cefepime for the treatment of pneumonia. The patient's peripheral eosinophilia and leukocytosis resolved promptly after discontinuation of cefepime and initiation of steroid treatment.

Novel method of calculating adjusted antibiotic use by microbiological burden.

OBJECTIVE: To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics. DESIGN: Retrospective, observational, cross-sectional study. SETTING: Hospitals in the southeastern United States. METHODS: AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL)-producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal ß-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared. RESULTS: Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016. CONCLUSIONS: The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.