A prospective randomized study comparing once- versus twice-daily amikacin dosing in critically ill adult and paediatric patients

Abstract

Three hundred and forty eight critically-ill patients with a documented Gram-negative infection were randomized to receive amikacin once- (od) or twice-daily (bd). The amikacin was given by slow intravenous injection in a daily dose of 20 mg/kg in patients under the age of one year (paediatric group) and 15 mg/kg in patients over the age of one year (adult group). Paediatric and adult patients on the od regimen received a loading dose of 25 and 20 mg/kg respectively. The dosages were subsequently adjusted to achieve desirable blood levels. Patients received other antibiotics as clinically indicated. Forty-eight patients were withdrawn from the study due to death or azotaemia occurring in the first 72 h. One hundred and fifty five patients (76 paediatric) received an od dose and 145 (65 paediatric) received a bd dose. The clinical cure rate was 83% in the od group compared to 66% in the bd group (P = 0.001). The bacteriological cure rate was 81% in the od group compared to 58% in the bd group (P = 0.005). In the paediatric sub-group the cure rate was higher with the od regimen (P = 0.002) but this difference was not statistically significant in the adult patients (P = 0.1). The serum creatinine rose in 35% of patients in the bd group compared to 21% in the od group (P = 0.05). Although audiometry was not performed there was no clinical evidence of ototoxicity in any of the patients. In conclusion od amikacin dosing resulted in a higher cure and less nephrotoxicity than conventional bd dosing.