Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock

Given the lack of clinical data to guide optimal dosing of vancomycin in critically ill patients with life-threatening infections, the objective was to characterise vancomycin pharmacodynamics in MRSA-associated septic shock. Cases were extracted from an observational, multicentre study in Canadian Intensive Care Units and included 35 adult patients with MRSA-associated septic shock who received vancomycin and had a measured serum concentration within the first 72 h of therapy. Univariate and multivariate analyses were used to assess variables predictive of in-hospital mortality. Patients who survived were significantly younger and had better renal function, lower probability of chronic obstructive pulmonary disease, higher probability of intravenous drug use, lower probability of healthcare-associated infection and lower APACHE II score. Survivors also received higher vancomycin doses and had higher serum troughs and AUC(24)/MIC values. The survival rate was 2.5-fold greater in patients who had vancomycin troughs >= 15 mg/L [70.6% (12/17) vs. 27.8% (5/18); P = 0.001]. Two significant AUC(24)/MIC thresholds for survival, >= 451 (P = 0.006) and >= 578 (P = 0.012), were identified by CART analysis. Only younger age (P = 0.028) and higher vancomycin AUC(24)/MIC (P = 0.045) were significant in multivariate analyses of survival. This study of vancomycin in critically ill patients supports the current recommendation for serum troughs of at least 15 mg/L and, in patients with septic shock, an AUC(24)/MIC threshold higher than the conventional 400. Improved survival was observed with the attainment of these pharmacodynamic targets. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.