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 AUC₂₄/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 AUC₂₄/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 AUC₂₄/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 AUC₂₄/MIC threshold higher than the conventional 400. Improved survival was observed with the attainment of these pharmacodynamic targets.