Pharmacokinetic assessment of vancomycin loading dose in critically ill patients

Abstract

The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose. However, considering only the body weight for dosing might be inadequate in critically ill patients due to pharmacokinetics changes. We sought to assess achieving optimal trough serum levels of vancomycin and AUC0–24/MIC in the first 24 h of treatment by using an LD based on population pharmacokinetic parameters of critically ill patients. We performed a concurrent cohort study over 22 months of patients with severe sepsis who received intravenous vancomycin. The patients were treated with three different strategies to initiate vancomycin: without an LD (group A), with an LD of 25 to 30 mg/kg (group B), and with an LD based on population pharmacokinetic parameters of the critically ill patient (group C). An optimal trough serum concentration was achieved in 5, 9, and 83% of patients in groups A, B, and C, respectively. The number of patients that reached optimal AUC0–24 was 2 of 18 (11%), 5 of 11 (46%), and 11 of 12 (92%) in groups A, B, and C, respectively. The statistical analysis for both parameters revealed significant differences in group C with respect to other groups. The administration of the LD calculated from population pharmacokinetic parameters from the beginning of therapy is a more efficient strategy to obtain adequate trough serum concentrations and AUC0–24/MIC in critical patients.