Background Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Results Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Conclusions Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This report describes a health-system pharmacy’s response to a natural disaster while staff members simultaneously prepared for the coronavirus disease 2019 (COVID-19) pandemic. By detailing our experience, we hope to help other institutions that are current facing or could encounter similar crises. Summary In early March 2020, a tornado destroyed the health system’s warehouse for storage of most clinical supplies, including personal protective equipment and fluids. The pharmacy purchasing team collaborated with suppliers and manufacturers to recover losses and establish alternative storage areas. Days later, the pharmacy department was forced to address the impending COVID-19 pandemic. Key elements of the COVID-19 response included reducing the potential for patient and staff virus exposure; overcoming challenges in sourcing of staff, personal protective equipment, and medications; and changing care delivery practices to maintain high-quality patient care while maximizing social distancing. The pharmacy department also created distance learning opportunities for 70 pharmacy students on rotations. After an initial plan, ongoing needs include adjustment in patient care activities if significant staff losses occur, when and how to resume clinical activities, and how to best utilize the resources accumulated. Elements of practice changes implemented to reduce COVID-19 threats to patients and pharmacy personnel have proven beneficial and will be further evaluated for potential continuation. Conclusion The pharmacy department’s efforts to respond to a natural disaster and unprecedented pandemic have proven successful to this point and have illuminated several lessons, including the necessity of cohesive department communication, staff flexibility, prioritization of teamwork, and external collaboration.

BackgroundCurrent guidelines recommend vancomycin (VAN) dosing to achieve AUC/MIC ratio ≥400 for patients (pts) with serious MRSA bloodstream infections (BSI), but supporting data were largely derived in single center retrospective studies. A recent study using a Bayesian approach to estimate the VAN AUC found that patients with MRSA BSI who had an AUCDAY2/MICBMD ≥ 650 or an AUCDAY2/MICETEST ≥ 320 had lower incidences of failure (Clin Infect Dis 59:666, 2014). This study prospectively evaluated if these VAN AUCDAY2/MIC targets were associated with lower incidences of failure (PROVIDE, Award number UM1AI104681, Antibacterial Resistance Leadership Group).MethodsProspective, multi-center (n = 14), observational study (2014–2106) of hospitalized adults with confirmed MRSA BSI treated with VAN ≥ 72h. Exclusion: (1) neutropenia; (2) cystic fibrosis; (3) renal replacement therapy; (4) APACHE-II score > 25; (5) previous MRSA BSI within 60 days. VAN exposures were estimated using maximum a posteriori probability procedure in ADAPT 5. MICBMD and MICETEST were performed at a central laboratory. Outcomes: failure (30-day mortality or MRSA BSI ≥ 7 days); acute kidney injury (AKI), ≥1.5 × increase in serum creatinine (Scr) among patients with a baseline SCR < 2.0mg/dl. The study was powered at 80% to detect a 17.5% difference in failure between AUCDAY2/MIC groups.ResultsAmong the 265 evaluable patients, mean (SD) age was 61 (17) and APACHE-II was 12 (6). Endocarditis was definite/possible in 29%. The MIC50/90 by BMD and ETEST were 1/1 and 1.5/1.5mg/l, respectively. Failure occurred in 18%; 26% had AKI. Mean (SD) VAN duration was 18 (14) days. Mean (SD) AUCDAY2 was 586.9 (235.5) and 44% and 73% of patients achieved an AUCDAY2/MICBMD ≥ 650 and AUCDAY2/MICETEST ≥ 320. In the multivariate analyses (Figure 1), failure was not significantly different between AUCDAY2/MIC groups. In contrast, AKI was significantly more common in patients with an AUCDAY2/ MICETEST > = 320.ConclusionAchievement of higher VAN AUCDAY2/MIC exposures for patients with MRSA BSIs were not associated with better outcomes and were found to result in increased AKI. Clinicians should assess the benefits vs. risks of using VAN regimens that confer high AUCDAY2/MIC exposures for patients with MRSA BSIs.Disclosures T. P. Lodise Jr., allergan: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; medicines company: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium; melinta: Consultant, Consulting fee; motif: Consultant and Scientific Advisor, Consulting fee; paratek: Consultant and Scientific Advisor, Consulting fee; nabriva: Consultant, Consulting fee; M. J. Zervos, Merck, Inc.: Investigator, Research grant; M. Scheetz, Bayer: Scientific Advisor, Consulting fee; V. Fowler Jr., Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, ...

We describe a method for measuring piperacillin and tazobactam that meets clinical validation standards. Quick turnaround time and excellent accuracy on a low-cost platform make this method more than adequate for use as a routine therapeutic drug monitoring tool.

BackgroundAnnually in the US alone, Clostridioides difficile infection (CDI) afflicts nearly 500,000 patients causing 29,000 deaths. Since early and aggressive interventions could save lives but are not optimally deployed in all patients, numerous studies have published predictive models for adverse outcomes. These models are usually developed at a single institution, and largely are not externally validated. This aim of this study was to validate the predictability for severe CDI with previously published risk scores in a multicenter cohort of patients with CDI.MethodsWe conducted a retrospective study on four separate inpatient cohorts with CDI from three distinct sites: the Universities of Michigan (2010–2012 and 2016), Chicago (2012), and Wisconsin (2012). The primary composite outcome was admission to an intensive care unit, colectomy, and/or death attributed to CDI within 30 days of positive test. Structured query and manual chart review abstracted data from the medical record at each site. Published CDI severity scores were assessed and compared with each other and the IDSA guideline definition of severe CDI. Sensitivity, specificity, area under the receiver operator characteristic curve (AuROC), precision-recall curves, and net reclassification index (NRI) were calculated to compare models.ResultsWe included 3,775 patients from the four cohorts (Table 1) and evaluated eight severity scores (Table 2). The IDSA (baseline comparator) model showed poor performance across cohorts(Table 3). Of the binary classification models, including those that were most predictive of the primary composite outcome, Jardin, performed poorly with minimal to no NRI improvement compared with IDSA. The continuous score models, Toro and ATLAS, performed better, but the AuROC varied by site by up to 17% (Table 3). The Gujja model varied the most: from most predictive in the University of Michigan 2010–2012 cohort to having no predictive value in the 2016 cohort (Table 3).ConclusionNo published CDI severity score showed stable, acceptable predictive ability across multiple cohorts/institutions. To maximize performance and clinical utility, future efforts should focus on a multicenter-derived and validated scoring system, and/or incorporate novel biomarkers. Disclosures All authors: No reported disclosures.