Performance of a Divided-Load Intravenous Vancomycin Dosing Strategy for Critically Ill Patients

Abstract

Current guidelines recommend vancomycin trough concentrations 15 to 20 µg/mL in complicated infections and all trough concentrations above 10 µg/mL. We assessed the performance of a novel divided-load protocol designed to attain target trough concentrations within 24 hours of initiation and prevent doses given at concentrations above the target range, in critically ill patients. The protocol was evaluated in 79 critically ill patients through retrospective medical record review. Vancomycin serum concentrations were drawn before the third dose after initiation and after any dosing change. Steady-state concentrations were drawn before the fifth or sixth doses. Vancomycin concentrations before the second dose were predicted using a nonparametric expectation maximization algorithm. Sixty-nine of 79 patients received scheduled doses, and 62 (90%) of the scheduled-dose patients attained therapeutic target concentrations 12 to 24 hours after therapy initiation. Eight scheduled-dose patients weighed > 150% of ideal body weight (IBW) and were significantly more likely to exhibit supratherapeutic trough concentrations before the fifth or sixth doses (P = .0004) compared with patients weighing ≤150% of IBW. Ten of 79 patients (8 dialysis dependent and 2 experiencing acute kidney injury) were dosed in response to measured serum drug concentrations drawn according to the divided-load protocol. All the 8 dialysis-dependent patients (100%) attained therapeutic concentrations 12 hours after therapy initiation. The divided-load vancomycin dosing strategy achieved measured trough concentrations 15 to 20 µg/mL for most critically ill patients within 24 hours of initial dosing, without allowing doses given during supratherapeutic concentrations.