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.

Which "weigh" to Go? Alternative Vancomycin Dosing Strategies in Obese Patients.

PurposeThis study aims to compare the performance of alternative weight-based vancomycin dosing strategies to traditional dosing in obese patients using area under the curve (AUC) monitoring. Methods: This retrospective study compared target attainment of an AUC between 400-600mcg*H/mL using alternative vancomycin dosing strategies. All patients received allometrically dosed vancomycin, with patient-specific AUCs calculated using 2 post-infusion steady-state vancomycin serum concentrations using the trapezoidal rule. Predicted AUCs were calculated using the following: 15 mg/kg total body weight (TBW), 15 mg/kg corrected body weight (CBW), and 12.5 mg/kg TBW. Predicted AUCs from the traditional 15 mg/kg TBW dosing were then compared to alternative dosing strategies using the predicted AUCs from 12.5 mg/kg TBW, 15 mg/kg CBW, and the actual AUCs calculated using allometrically scaled vancomycin dosing. The primary outcome was attainment of initial AUC within the target range of 400-600mcg*H/mL for each dosing method. Results: Eighty-four patients were included. When AUCs were compared to traditional 15 mg/kg dosing strategy, the CBW, 12.5 mg/kg, and allometric dosing strategies were significantly more likely to result in initial attainment of an AUC within a target range of 400-600 mcg*H/mL (P = 0.0003, 0.0135, and 0.0088, respectively). No significant differences were seen between each of the alternative dosing methods (P = 0.73). Conclusion: The 3 alternative vancomycin dosing strategies examined were all significantly more likely to achieve an initial AUC within the target range compared to traditional vancomycin dosing in obese patients. Clinicians should strongly consider one of these alternative dosing strategies for obese patients as opposed to traditional vancomycin dosing.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in Non-Hospital Care Settings in 2021.

The scope of antimicrobial stewardship programs has expanded beyond the acute hospital setting. The need to optimize antimicrobial use in emergency departments, urgent, primary, and specialty care clinics, nursing homes, and long-term care facilities prompted the development of core elements of stewardship programs in these settings. Identifying the most innovative and well-designed stewardship literature in these novel stewardship areas can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network evaluated antimicrobial stewardship-related, peer-reviewed literature published in 2021 that detailed actionable interventions specific to the nonhospital setting. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for expansion of antimicrobial stewardship programs beyond the acute hospital setting.

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.

Early Experience With Interleukin-6 Receptor Antagonists in Patients With COVID-19 Admitted to a Community Hospital.

Background/objective: The efficacy of interleukin-6 (IL-6) inhibitors in hospitalized patients with severe coronavirus disease 2019 (COVID-19) pneumonitis is unclear. Method: This retrospective, observational cohort study included patients hospitalized at a community hospital with COVID-19 pneumonia from March 2020 to May 2020. All patients were treated with standard of care (SOC), and a nonrandomly selected subset of patients also received an IL-6 inhibitor. The primary outcome was clinical response, defined as an improvement of at least 2 categories relative to baseline on a 7-category ordinal scale up to hospital discharge or 30 days. In adjusted analyses, logistic and linear regression models were conducted, controlling for covariates of hospital length of stay (LOS), intensive care unit (ICU) care, ICU LOS, gender, age, race, and Charlson Comorbidity Index. Results: A total of 133 patients met inclusion criteria. In all, 30 patients received an IL-6 inhibitor plus SOC. There was no statistical difference in clinical outcome between groups as 76.7% in the SOC alone group and 70.0% in the IL-6 inhibitor group met the defined endpoints for clinical response (P = 0.477). In the adjusted analysis, patients treated with IL-6 inhibitors were approximately 4 times more likely to meet the primary endpoint compared with patients with SOC alone (adj. odds ratio = 4.325; P = 0.038, 95% confidence interval = [1.09-17.18]). Conclusions: Compared with SOC alone, IL-6 inhibitors were not associated with a significant clinical response. However, after adjusting for covariates, this study suggests that the initiation of IL-6 inhibitors in patients with early COVID-19 pneumonitis before progression to the ICU may be associated with improved clinical status.

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.

Evaluating the Safety of Trough Versus Area Under the Curve (AUC)-Based Dosing Method of Vancomycin With Concomitant Piperacillin-Tazobactam.

Background: Vancomycin and piperacillin-tazobactam (VPT) is a common antibiotic combination used in hospitals, and there has been increasing data indicating that the combination is associated with increased rates of acute kidney injury (AKI). It is unclear if the dosing method of vancomycin would mitigate the risk of AKI seen with VPT. Objective: To observe and compare incidence of AKI in patients on VPT when using the trough-based dosing method versus the area-under-the-curve (AUC)-based dosing method. Methods: This was a multi-center, retrospective, observational study at 3 community hospitals. Adults receiving at least 48 hours of VPT were included. Patients with severe renal dysfunction, pregnant patients, prisoners, and patients with central nervous system infections, or malignancy were excluded. The primary outcome was incidence of AKI as defined by the Infectious Disease Society of America (IDSA) criteria. Results: A total of 300 patients were included in the study; 150 patients in both the trough and AUC groups. A total of 23 patients (15%) in the trough group and 17 patients (11%) in the AUC group met the primary outcome (odds ratio [OR]: 0.7058, 95% confidence interval [CI]: [0.3603, 1.3826], P = .3098). Conclusion and Relevance: The incidence of AKI was lower in the AUC group compared with the trough group; however, this was not significant. The results of our study suggest that there is no difference between incidence of AKI when using trough- or AUC-based dosing in those receiving VPT. Because of the small sample size and retrospective nature of the study, more data are needed.

Evaluation of Monoclonal Antibodies in Preventing Hospitalizations, Emergency Department Visits, and Mortality in High-Risk COVID-19 Patients.

Background: The coronavirus disease 2019 (COVID-19) is a novel coronavirus that has caused an unprecedented global pandemic, with few treatment options currently available. Neutralizing monoclonal antibodies (mAbs) are a promising treatment approach to reduce hospitalizations in high-risk patients with mild-to-moderate COVID-19 infections. Objective: The primary objective is to compare hospitalization rates of high-risk patients who tested positive for COVID-19 within 28 days between those who received mAb infusions versus those who did not. Secondary objectives were emergency department (ED) visits and mortality within 28 days of a positive test. Methods: This single-center, institutional review board-approved, retrospective, observational cohort study included patients aged 19 years and older who tested positive for COVID-19 between December 2, 2020 and February 28, 2021. Patients who received the mAbs bamlanivimab or casirivimab/imdevimab were compared with patients who did not receive mAb infusions to examine hospitalization rates, ED visits, and mortality within 28 days of the positive COVID-19 test. Results: A total of 2780 patients were evaluated for inclusion using electronic chart review via Cerner. Of the 1612 patients who met inclusion criteria, 568 received an mAb infusion (mAb group) and 1044 did not (non-mAb group). Baseline characteristics were similar between the 2 groups. Of the patients in the mAb group, 34 (6%) were hospitalized versus 397 (38%) in the non-mAb group. Patients with ED visits included 111 (20%) and 672 (64%) in the mAb and non-mAb groups, respectively. Finally, 5 patients in the mAb group experienced mortality (0.9%) versus 83 (8%) in the non-mAb group. Each endpoint achieved statistical significance with a P value of <0.0001. Conclusion: Monoclonal antibody infusions are effective in preventing hospitalization, ED visits, and mortality in high-risk patients with mild-to-moderate COVID-19.

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.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2019.

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one's institution.

Comparison of Vancomycin Treatment Failures for Methicillin-Resistant Staphylococcus aureus Bacteremia Stratified by Minimum Inhibitory Concentration.

Background: Optimal treatment of methicillin-resistant Staphylococcus aureus bacteremias (MRSABs) with vancomycin minimum inhibitory concentrations (MICs) high within the susceptible range is of concern due to the high rate of mortality and increased prevalence. Objective: The purpose of this study is to evaluate vancomycin treatment failures in patients with MRSAB stratified by vancomycin MIC. Methods: In this retrospective chart review, patients ≥19 years of age with MRSAB between July 2010 and December 2016 were included if they received intravenous vancomycin for ≥72 hours. Vancomycin treatment failures were compared between patients with vancomycin MICs of ≤1 mg/L and 2 mg/L. Vancomycin treatment failure was defined as microbiological failure at 7 days. Inpatient mortality, 30-day readmission, vancomycin-associated nephrotoxicity, and early bacteremia clearance at 48 to 96 hours were assessed as secondary endpoints. Results: Fifty-eight patients were included in the vancomycin MIC ≤1 mg/L group and 22 patients in the vancomycin MIC 2 mg/L group. No significant difference was found in vancomycin treatment failures at 7 days between groups (88% vs 91%, respectively; P = .850). At 96 hours, there was no significant difference in vancomycin treatment failures between groups (72% vs 90%, respectively; P = .127). No significant difference was found in mortality (P > .99) or 30-day readmission (P > .99). Conclusions: In this study, vancomycin treatment failures were not more prevalent in patients with vancomycin MIC of 2 mg/L at 7 days. Regardless of MIC, antibiotics should be switched to an alternative agent at 7 days for persistent bacteremia.

Allometric versus consensus guideline dosing in achieving target vancomycin trough concentrations.

PURPOSE: Results of a study comparing the performance of allometric versus consensus guideline-recommended vancomycin dosing in achieving initial trough concentrations within the desired range are reported. METHODS: A retrospective study was conducted to compare selected outcomes with 2 vancomycin dosing methods: (1) dosing by total body weight, as recommended in current consensus guidelines, and (2) a new empirical vancomycin dosing strategy grounded in allometry (the study of the relationship between body size and physiology). The primary outcome was attainment of an initial vancomycin trough concentration within the target range (10-20 mg/L). Rates of nephrotoxicity associated with the 2 dosing methods were compared. RESULTS: Allometric dosing resulted in 77% of the evaluated patient sample (n = 81) achieving vancomycin trough concentration targets at the initial measurement, as compared with a target attainment rate of 57% (n = 81) with guideline-recommended dosing (p = 0.0121); the rate of target attainment in obese patients was also improved with allometric dosing (73% versus 46%, p = 0.0327). Nephrotoxicity rates did not differ significantly between the 2 groups, but a lower rate was observed with allometric versus guideline-based dosing (1.2% versus 7.4%, p = 0.0584). CONCLUSION: In hospitalized adults, allometric vancomycin dosing achieved a higher frequency of initial vancomycin trough concentrations within the target range of 10-20 mg/L, compared with dosing as recommended by consensus guidelines. The difference between methods in the percentage of troughs within the target range was most pronounced in obese patients.

Drug interactions between common illicit drugs and prescription therapies.

OBJECTIVE: The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. METHODS: Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4-methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drug-drug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. RESULTS: The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. CONCLUSION: Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. SCIENTIFIC SIGNIFICANCE: Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.