Clinical pharmacology and efficacy of vancomycin in pediatric patients

Abstract

The emergence of staphylococci resistant to multiple antibiotics and the lack of information on pharmacology, efficacy, and safety of vancomycin in pediatric patients prompted this study. In vitro susceptibility studies showed that 33 to 50% of staphylococci tested were resistant to nafcillin, methicillin, cephalothin, and gentamicin, whereas none were resistant to vancomycin. Pharmacokinetic data of vancomycin were evaluated in 55 pediatric patients and was characterized by the two-compartment open-system kinetic model. Mean peak serum concentrations in infants and children after 10 and 15 mg/kg doses ranged from 25.2 to 32.5 μg/ml. The 10 mg/kg dose in newborn infants resulted in substantially lower peak values. Mean serum elimination phase half-life values correlated inversely with gestational and chronologic age and ranged from 2.2 to 9.8 hours. The CSF penetration in three infants with staphylococcal ventriculoperitoneal shunt infections ranged from 7 to 21%. Sixteen patients with staphylococcal diseases were successfully treated with vancomycin. In these patients peak serum vancomycin concentrations greater than 25 μg/ml and trough concentrations less than 12 μg/ml produced satisfactory inhibitory and bactericidal titers. Laboratory studies and auditory function tests did not reveal any drug-related abnormalities. Dosage schedules were formulated from these data. Indications and precautions for vancomycin therapy in infants and children are presented. The emergence of staphylococci resistant to multiple antibiotics and the lack of information on pharmacology, efficacy, and safety of vancomycin in pediatric patients prompted this study. In vitro susceptibility studies showed that 33 to 50% of staphylococci tested were resistant to nafcillin, methicillin, cephalothin, and gentamicin, whereas none were resistant to vancomycin. Pharmacokinetic data of vancomycin were evaluated in 55 pediatric patients and was characterized by the two-compartment open-system kinetic model. Mean peak serum concentrations in infants and children after 10 and 15 mg/kg doses ranged from 25.2 to 32.5 μg/ml. The 10 mg/kg dose in newborn infants resulted in substantially lower peak values. Mean serum elimination phase half-life values correlated inversely with gestational and chronologic age and ranged from 2.2 to 9.8 hours. The CSF penetration in three infants with staphylococcal ventriculoperitoneal shunt infections ranged from 7 to 21%. Sixteen patients with staphylococcal diseases were successfully treated with vancomycin. In these patients peak serum vancomycin concentrations greater than 25 μg/ml and trough concentrations less than 12 μg/ml produced satisfactory inhibitory and bactericidal titers. Laboratory studies and auditory function tests did not reveal any drug-related abnormalities. Dosage schedules were formulated from these data. Indications and precautions for vancomycin therapy in infants and children are presented.