Is Trough Level Adequate for Determining Vancomycin Dosing in MRSA Bacteremia?

Neil M. Ampel, MD

In a retrospective cohort study, the vancomycin trough level was not predictive of outcome, but the AUC/MIC was.

Most vancomycin dosing schemes for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) are designed to achieve a target area-under-the-curve/minimum-inhibitory-concentration ratio (AUC/MIC) ≥400. However, in clinical practice, a trough level (Cmin) of 15–20 mg/L has been used as a surrogate.

In a manufacturer-funded retrospective cohort study involving 123 adults who received vancomycin while hospitalized with a MRSA BSI between January 2005 and June 2009, researchers evaluated the relationship between various vancomycin exposure variables and outcomes. The variables Cmin and AUC were estimated for each patient using ADAPT 5, a pharmacokinetic/pharmacodynamic software program. With ADAPT, the observed and predicted concentrations of vancomycin were highly correlated (R2=0.99), whereas with the standard approach based on daily vancomycin dose and an estimation of creatinine clearance, the correlation between observed and predicted values was much lower (R2=0.32).

Analysis using Classification and Regression Tree (CART)-derived breakpoints revealed that the Cmin/MIC was not associated with treatment outcomes. However, the risk for treatment failure (i.e., 30-day mortality, bacteremia duration ≥7 days, or recurrence) was 50% lower in patients with an AUC/MIC above the CART-derived values than in those with an AUC/MIC below these values.

Citation(s):

Lodise TP et al. Vancomycin exposure in patients with methicillin-resistant Staphylococcus aureus bloodstream infections: How much is enough? Clin Infect Dis 2014 Sep 1; 59:666.