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Master of Public Health

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)

AUTHORS

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 , Holland TL , , . Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 6 3; ().

ABSTRACT

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 ≤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.

TRIAL REGISTRATION: Registration was not required for this study.

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