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).

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 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.

• Authors: Thomas P Lodise, Susan L Rosenkranz, Matthew Finnemeyer, Scott Evans, Matthew Sims, Marcus J Zervos, C Buddy Creech, Pratish C Patel, Michael Keefer, Paul Riska, Fernanda P Silveira, Marc Scheetz, Richard G Wunderink, Martin Rodriguez, John Schrank, Susan C Bleasdale, Sara Schultz, Michelle Barron, Ann Stapleton, Dannah Wray, Henry Chambers, Vance G Fowler, Thomas L Holland
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 70 Issue 8 Pg. 1536-1545 (04 10 2020) ISSN: 1537-6591 [Electronic] United States
• PMID: 31157370 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Vancomycin

Topics

• Adult
• Anti-Bacterial Agents (therapeutic use)
• Bacteremia (drug therapy)
• Humans
• Methicillin-Resistant Staphylococcus aureus
• Microbial Sensitivity Tests
• Prospective Studies
• Retrospective Studies
• Staphylococcal Infections (drug therapy)
• Treatment Outcome
• Vancomycin (therapeutic use)