Reevaluation of Kanamycin Dosage in Infants and Children

Abstract

It was recently reported that the dosage of kanamycin formerly recommended for neonates of 7.5 mg/kg every 12 h did not produce therapeutic serum concentrations of 15 to 25 μg/ml, but a larger dosage of 10 mg/kg every 12 h was required. Reevaluation of the pharmacokinetics of kanamycin in infants and children was therefore undertaken. Sixteen time-concentration curves after a dose of 5 mg/kg were obtained from patients 2 months to 12 years of age; the mean peak serum kanamycin concentration was 10.9 (range, 3.6 to 17.9) μg/ml at 0.5 h. Ten time-concentration curves were obtained after a dose of 10 mg/kg; the mean peak serum concentration was 17.6 (range, 8.4 to 30) μg/ml. Eight patients were studied on successive days, and there was doubling of the 1-h peak serum concentration when the dose of kanamycin was increased from 5 to 10 mg/kg. Standard serum bactericidal tests were done against Escherichia coli and Enterobacter cloacae strains, each with a minimal bactericidal concentration of 5 μg of kanamycin per ml. All 3 sera containing 21 μg or more of kanamycin per ml demonstrated a bactericidal titer, whereas only 2 of 23 sera containing less than 21 μg of kanamycin per ml did so. The currently recommended dosage of kanamycin for infants and children fails to produce serum concentrations in the therapeutic range, and preliminary data suggest that the dosage should be increased to 10 mg/kg per dose every 8 h.