Pharmacokinetic/pharmacodynamic (PK/PD) Determinants of Vancomycin Efficacy in Enterococcal Bacteremia [PublishAheadOfPrint]

Background. While pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections, scant data are available to guide therapy for other gram positive infections.

Methods. A retrospective single-centre cohort of patients with Enterococcus spp. bacteremia hospitalized between 1^st January 2009 and 31^st May 2015 were studied. Average vancomycin AUC_0-24hrs was computed using a Bayesian approach. MIC was determined by gradient diffusion (E-test, bioMerieux) and the average AUC_0-24hrs/MIC over the initial 72 hours 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 vancomycin AUC_0-24hrs/MIC associated with 30-day mortality.

Results. Fifty-seven patients with enterococcal bacteremia (32 E. faecium, 21 E. faecalis, 4 other Enteroccocus spp.) were studied. The median vancomycin MIC was 0.75 mg/L (range 0.38-3 mg/L). All-cause 30-day mortality occurred in 10 out of 57 patients (17.5%). A CART-derived vancomycin AUC/MIC_Etest of ≥389 was associated with reduced mortality (P= 0.017); failure to achieve this independently predicted 30-day mortality [OR 5.65 (95% CI 1.18-27.03), P= 0.03].

Conclusion. We found that a vancomycin AUC/MIC_Etest (≥389), achieved within 72 hours, was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety.

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