Wide variation in single, daily-dose aminoglycoside pharmacokinetics in patients with burn injuries

Five to seven mg/kg single, daily-dose aminoglycoside regimens have been recently advocated as effective alternatives to traditional aminoglycoside regimens. The rationale for single, daily-dose aminoglycoside therapy is to produce an optimal ratio between aminoglycoside peak concentrations (C(max)) and pathogen minimal inhibitory concentration to maximize bacterial killing and to produce an aminoglycoside-free period during the 24-hour dosing interval. Single, daily dose aminoglycoside therapy has not been recommended to date for use in the population of patients with burn injuries. The purpose of this study was to determine the magnitude and variability of aminoglycoside C(max) and the duration of the aminoglycoside-free period after simulated single, daily-dose regimens in patients with burn injuries. Fifty-two patients receiving gentamicin or tobramycin in the burn unit were studied retrospectively to determine the individualized pharmacokinetic parameters and the simulated C(max) and 24-hour after the dose trough minimum concentrations for 5 and 7 mg/kg single, daily-dose aminoglycoside regimens. Patients were only included in the final analysis if they had been treated for burn wound infections and exhibited a calculated creatinine clearance exceeding 60 ml/min (N = 40). Mean [percentage coefficient of variation] C(max)/minimum concentrations were 15.4[30.5]/0.03[200.0] and 21.6[30.6]/0.04[200.0] mg/L for 5 and 7 mg/kg daily doses, respectively. The mean coefficient of variation time to reach an extrapolated concentration of 0.1 mg/L was 15.9[30.8] hours and 17.0[30.6] hours for the 5 and 7 mg/kg daily doses, respectively. Substantial variability in aminoglycoside C(max) and duration of the aminoglycoside-free period was observed. These data suggest that many patients with burn injuries are not candidates for single, daily-dose aminoglycoside therapy because of restrictive creatinine clearance criteria and pronounced variability in length of the aminoglycoside-free interval. If single, daily-dose aminoglycoside therapy is to be used in this patient population, therapeutic drug monitoring is recommended to screen for appropriate candidates and to optimize C(max) and minimal inhibitory concentration ratios and duration of the aminoglycoside-free interval.