Daptomycin is approved for treatment of complicated skin/skin structure infections and Staphylococcus aureus bloodstream infections (bacteremia) in adults. This study was undertaken to determine the pharmacokinetics of daptomycin in pediatric patients 3–24 months of age with proven/suspected bacterial infection.
In this phase 1, multicenter, open-label, noncomparative pharmacokinetic and safety study, patients were enrolled in 3 age groups: 3–6, 7–12 and 13–24 months. Intravenous daptomycin (single dose) was infused over 30 minutes at 6 mg/kg in subjects 13–24 months of age and at 4 mg/kg in the younger groups. Blood was collected for analysis of daptomycin concentrations.
Twenty-four subjects received daptomycin. Daptomycin exposures (area under the curve0–∞) in children 3–6 and 7–12 months of age receiving 4 mg/kg were similar (215 and 219 μg·h/mL, respectively). Children 13–24 months of age receiving a higher dose, 6 mg/kg, had higher exposures (282 μg·h/mL). Mean maximum plasma concentrations in the age groups were 38.7, 37.1 and 67.0 μg/mL, respectively. Daptomycin exposures based on mg/kg dosing were lower than previously reported for older children and adults, likely because of increased clearance and volume of distribution and decreased apparent elimination half-life. Single-dose daptomycin 4 and 6 mg/kg was well tolerated and was not associated with clinical or laboratory adverse events.
To match known clinically and microbiologically effective exposures in adults, infants require higher mg/kg daptomycin doses. Daptomycin safety and efficacy have not been established in pediatric patients. Pediatric clinical trials are ongoing.