Once versus thrice daily intramuscular gentamicin in children with systemic infections

Objective: To evaluate the clinical efficacy, pharmacokinetic profiles and nephrotoxicity of once daily versus thrice daily doses of intramuscular gentamicin in infants and children. Design: A randomized trial. Subjects: Patients between ages of one month and eight years with clinically suspected or proven severe bacterial infection with no prior history of aminoglycoside therapy. Interventions: Patients were randomized to receive gentamicin once daily or thrice daily with the same total daily dose of 6 mg/kg body weight. Main Outcome Measures: Clinical efficacy, pharmacokinetic profiles and nephrotoxicity. Results: A total of 107 children were enrolled in the study, and randomized to the intervention. The baseline characteristics were comparable. Only 74 patients who continued to receive gentamicin therapy beyond 48 hours were evaluated. A favourable clinical response was found in 27/35 (77%) in the OD group and 32/39 (82%) in the TD group (p=0.814). Only 52 patients (26 in each group) had pharmacokinetic profiles determined. A statistically significantly higher mean (SD) serum peak concentration was present in the OD [6.45 (1.95) μg/ml] group compared to the TD group [2.75 (1.3) μg/ml] (p<0.001). Through concentrations in both groups were within the desired levels of less than 2 μg/ml. Evidence of apparent nephrotoxicity was absent in both groups. Conclusions: Compared to the recommended thrice daily dosing, once daily administration of intramuscular gentamicin in children achieves better therapeutic drug levels. The once daily intramuscular dose is more convenient for both patients and health workers, is less costly and should therefore be recommended for use in children.