Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
From the *Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, School of Medicine, and Rady Children’s Hospital, San Diego, CA; †Department of Clinical Research, Cubist Pharmaceuticals, Lexington, MA; and ‡Department of Pediatrics, University of Arkansas for Medical Sciences College of Medicine, University of Arkansas, Little Rock, AR.
Accepted for publication February 14, 2014.
Previously presented at ID Week, October 17–21, 2012, San Diego, CA and the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), March 31–April 3, 2012, London, United Kingdom.
This study was funded by Cubist Pharmaceuticals, Lexington, MA.
J.S.B’s employer, the University of California, San Diego, has clinical research and consulting contracts with Cubist Pharmaceuticals. D.B. is a former employee of Cubist Pharmaceuticals. P.B. is a current employee of Cubist Pharmaceuticals. R.J.’s employer, Arkansas Children’s Hospital Research Institute, has clinical research contracts with Cubist Pharmaceuticals. The authors have no other funding or conflicts of interest to disclose.
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Author for correspondence: John S. Bradley, MD, 3020 Children’s Way, MC 5041, San Diego, CA 92123. E-mail: email@example.com.