Study 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.
Design: Meta-analysis of 14 observational cohort studies.
Patients: 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.
Measurements and main 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.
Conclusion: 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.
Keywords: MRSA; Staphylococcus aureus; meta-analysis; pharmacokinetics; therapeutic drug monitoring; trough; vancomycin.
© 2015 Pharmacotherapy Publications, Inc.