The Emperor's New Clothes: Prospective Observational Evaluation of the Association between Initial Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE)
Lodise TP, Rosenkranz SL, Finnemeyer M, Evans S, Sims M, Zervos MJ, Creech CB, Patel PC, Keefer M, Riska P, Silveira FP, Scheetz M, Wunderink RG, Rodriguez M, Schrank J, Bleasdale SC, Schultz S, Barron M, Stapleton A, Wray D, Chambers H, Fowler V, and Holland TL. The Emperor's New Clothes: Prospective Observational Evaluation of the Association between Initial Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE). Clin Infect Dis 2019; Epub ahead of print.
Clinical infectious diseases
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 MRSA bacteremic patients. METHODS: 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 pre-specified 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
ePub ahead of print