Vancomycin Trough Concentration as a Predictor of Clinical Outcomes in Patients with Staphylococcus aureus Bacteremia: A Meta-analysis of Observational Studies.
OBJECTIVE
To determine the strength of evidence for better clinical outcomes in patients with Staphylococcus aureus bacteremia who had vancomycin trough levels of 15-20 mg/L.


METHODS
Meta-analysis of 14 observational cohort studies.


METHODS
A total of 1677 patients, representing geriatric and unspecified inpatients, who received standard dosing of vancomycin for the treatment of S. aureus bacteremia and who had trough level goals of 15-20 mg/L.


RESULTS
The treatment variables examined in the analysis were vancomycin trough concentrations and 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC) values. The outcomes of interest were mortality, persistent bacteremia, and treatment failure. Mortality was defined as 30-day mortality, in-hospital mortality, or a comparable measure; persistent bacteremia was defined as bacteremia lasting at least 7 days after the initiation of vancomycin; treatment failure was defined as a composite end point that included at least persistent bacteremia and mortality, as previously defined. Higher vancomycin trough levels (15 mg/L or greater or based on MIC) were not associated with significantly reduced treatment failure, persistent bacteremia, or mortality. Higher AUC:MIC values were associated with significantly reduced treatment failure (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.31-0.53), persistent bacteremia (OR 0.53, 95% CI 0.33-0.86), and mortality (OR 0.47, 95% CI 0.33-0.65). The weighted mean ± SD AUC:MIC threshold defined by regression analyses in the included studies was 418 ± 88 hours, which supports the current goal of 400 hours or more.


CONCLUSIONS
Vancomycin trough concentrations do not have sufficient evidence to support their use as the primary guide in vancomycin dosing. Dosing should instead focus on AUC:MIC values, which have strong evidence of benefit.
College of Pharmacy, University of Florida, Gainesville, Florida.
John P
JP
Prybylski
D000900:Anti-Bacterial Agents / Q000097:blood* / Q000627:therapeutic use*; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D016903:Drug Monitoring; D017052:Hospital Mortality; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus; D008826:Microbial Sensitivity Tests; D064887:Observational Studies as Topic; D016017:Odds Ratio; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D017211:Treatment Failure; D014640:Vancomycin / Q000097:blood* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014640:Vancomycin
MRSA; Staphylococcus aureus; meta-analysis; pharmacokinetics; therapeutic drug monitoring; trough; vancomycin