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Observational Study
. 2020 Apr 10;70(8):1536-1545.
doi: 10.1093/cid/ciz460.

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  1 , Susan L Rosenkranz  2 , Matthew Finnemeyer  2 , Scott Evans  3 , Matthew Sims  4 , Marcus J Zervos  5 , C Buddy Creech  6 , Pratish C Patel  6 , Michael Keefer  7 , Paul Riska  8 , Fernanda P Silveira  9 , Marc Scheetz  10   11 , Richard G Wunderink  11 , Martin Rodriguez  12 , John Schrank  13 , Susan C Bleasdale  14 , Sara Schultz  15 , Michelle Barron  16 , Ann Stapleton  17 , Dannah Wray  18 , Henry Chambers  19 , Vance G Fowler  20   21 , Thomas L Holland  20   21
Affiliations
Observational Study

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 et al. Clin Infect Dis. .

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.

Keywords: MRSA; bacteremia; outcomes; vancomycin.

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Figures

Figure 1.
Figure 1.
Desirability of outcome ranking analysis by area under the curve quintiles: bottom quintile, 94.3–≤389.8; second quintile, >389.8–≤515.7; third quintile, >515.7–≤620.8; fourth quintile, >620.8–≤757.4; top quintile, >757.4–≤1755.0. Abbreviations: AKI, acute kidney injury; Q, quintile; TF, treatment failure; TS, treatment success
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