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Clin Infect Dis. 2019 Jun 3. pii: ciz460. doi: 10.1093/cid/ciz460. [Epub ahead of print]

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).

Author information

1
Albany College of Pharmacy and Health Sciences, Albany, NY.
2
Harvard T.H. Chan School of Public Health, Boston, MA.
3
Department of Epidemiology and Biostatistics, Biostatistics Center, George Washington University, Washington, DC.
4
William Beaumont Hospital, Royal Oak, MI.
5
Henry Ford Health System, Detroit, MI.
6
Vanderbilt University Medical Center, Nashville, TN.
7
University of Rochester Medical Center, Rochester, NY.
8
Montefiore Medical Center, Bronx, NY.
9
University of Pittsburgh, Pittsburgh, PA.
10
Midwestern University Chicago College of Pharmacy, Department of Pharmacy Practice, Chicago College of Osteopathic Medicine, Department of Pharmacology, Downers Grove, IL.
11
Northwestern Memorial Hospital, Chicago, IL.
12
University of Alabama Birmingham Department of Medicine, Birmingham, AL.
13
Greenville Hospital System University Medical Center, Greenville, SC.
14
University of Illinois Hospital and Health Sciences System, Chicago, IL.
15
Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA.
16
University of Colorado Denver, Aurora, CO.
17
University of Washington Medical Center, Seattle, WA.
18
Medical University of South Carolina, Charleston, SC.
19
San Francisco General Hospital, San Francisco, CA.
20
Duke Clinical Research Institute, Durham, NC.
21
Duke University Medical Center, Durham, NC.

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.

KEYWORDS:

MRSA; bacteremia; outcomes; vancomycin

PMID:
31157370
DOI:
10.1093/cid/ciz460

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