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Reevaluation of kanamycin dosage in infants and children
Insights
The current kanamycin dosage for infants and children is insufficient for therapeutic effect. Increasing the dose to 10 mg/kg every 8 hours may achieve necessary serum concentrations for effective treatment.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- The recommended kanamycin dosage for neonates (7.5 mg/kg every 12 hours) may not achieve therapeutic serum concentrations (15-25 µg/ml).
- A higher dosage of 10 mg/kg every 12 hours has been suggested for neonates.
Purpose of the Study:
- To reevaluate the pharmacokinetics of kanamycin in infants and children.
- To determine optimal kanamycin dosing for pediatric patients.
Main Methods:
- Kanamycin pharmacokinetics were studied in patients aged 2 months to 12 years.
- Time-concentration curves were generated after doses of 5 mg/kg and 10 mg/kg.
- Serum bactericidal tests were performed against Escherichia coli and Enterobacter cloacae.
Main Results:
- A 5 mg/kg dose yielded a mean peak serum kanamycin concentration of 10.9 µg/ml.
- A 10 mg/kg dose resulted in a mean peak serum concentration of 17.6 µg/ml.
- Sera with ≥21 µg/ml demonstrated bactericidal activity, unlike those with <21 µg/ml.
Conclusions:
- The current kanamycin dosage for infants and children is inadequate for therapeutic serum concentrations.
- Preliminary data suggest increasing the dosage to 10 mg/kg every 8 hours for improved efficacy.
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 mug/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) mug/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) mug/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 mug of kanamycin per ml. All 3 sera containing 21 mug or more of kanamycin per ml demonstrated a bactericidal titer, whereas only 2 of 23 sera containing less than 21 mug 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.