The Emperor's New Clothes: PRospective Observational Evaluation of the Association Between Initial VancomycIn Exposure and Failure Rates Among ADult HospitalizEd Patients With Methicillin-resistant Staphylococcus aureus Bloodstream Infections (PROVIDE)

Thomas P. Lodise, Albany College of Pharmacy and Health Sciences
Susan L. Rosenkranz, Harvard T.H. Chan School of Public Health
Matthew Finnemeyer, Harvard T.H. Chan School of Public Health
Scott Evans, The George Washington University
Matthew Sims, William Beaumont Hospital
Marcus J. Zervos, Henry Ford Health System
C. Buddy Creech, Vanderbilt University Medical Center
Pratish C. Patel, Vanderbilt University Medical Center
Michael Keefer, University of Rochester Medical Center
Paul Riska, Montefiore Medical Center
Fernanda P. Silveira, University of Pittsburgh
Marc Scheetz, Chicago College of Osteopathic Medicine
Richard G. Wunderink, Northwestern Memorial Hospital
Martin Rodriguez, The University of Alabama at Birmingham
John Schrank, Greenville Hospital System
Susan C. Bleasdale, University of Illinois at Chicago
Sara Schultz, Drexel University College of Medicine
Michelle Barron, University of Colorado Denver
Ann Stapleton, University of Washington Medical Center
Dannah Wray, Medical University of South Carolina
Henry Chambers, San Francisco General Hospital and Trauma Center
Vance G. Fowler, Duke Clinical Research Institute
Thomas L. Holland, Duke Clinical Research Institute


© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: 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.