Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia

Abstract

While pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistant <i>Staphylococcus aureus</i> infections, scant data are available to guide therapy for other Gram-positive infections. A retrospective single-center cohort of patients with <i>Enterococcus</i> bacteremia hospitalized between 1 January 2009 and 31 May 2015 were studied. The average vancomycin AUC_0-24 was computed using a Bayesian approach. The MIC was determined by gradient diffusion (Etest; bioMérieux), and the average AUC_0-24/MIC value over the initial 72 h of therapy was calculated. We assessed 30-day all-cause mortality as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC_0-24/MIC value associated with 30-day mortality. Fifty-seven patients with enterococcal bacteremia (32 <i>E. faecium</i>, 21 <i>E. faecalis</i>, and 4 other <i>Enterococcus</i> spp.) were studied. The median vancomycin MIC was 0.75 mg/liter (range, 0.38 to 3 mg/liter). All-cause 30-day mortality occurred in 10 of 57 patients (17.5%). A CART-derived vancomycin AUC/MIC_Etest value of ≥389 was associated with reduced mortality (<i>P</i> = 0.017); failure to achieve this independently predicted 30-day mortality (odds ratio, 6.83 [95% confidence interval = 1.51 to 30.84]; <i>P</i> = 0.01). We found that a vancomycin AUC/MIC_Etest value of ≥389 achieved within 72 h was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety.