title: Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock.
abstract: 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.
authors: Faculty of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. zelenits@ms.umanitoba.ca
authors: Sheryl
authors: S
authors: Zelenitsky
authors: Ethan
authors: E
authors: Rubinstein
authors: Robert
authors: R
authors: Ariano
authors: Harris
authors: H
authors: Iacovides
authors: Peter
authors: P
authors: Dodek
authors: Yazdan
authors: Y
authors: Mirzanejad
authors: Anand
authors: A
authors: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002170:Canada; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D016019:Survival Analysis; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin