Pharmacokinetics and safety of meropenem in young infants with intra-abdominal infections

Meropenem is approved for treatment of complicated abdominal infections in pediatric patients and adults. The primary objective of this study is to characterize meropenem multiple-dose PK and preliminary safety in young infants. Infants < 91 days of age with suspected or documented complicated intra-abdominal infections were eligible for the study. Infants with renal dysfunction or history of seizures were excluded. Population and individual subject (Bayesian) PK parameters were estimated using NONMEM. Data including 99 meropenem concentrations on the first 22 infants enrolled are presented. Dosing was based on both gestational age and postnatal age: 3 infants received 20 mg/kg q12 h, 13 received 20 mg/kg q8 h, 1 received 30 mg/kg q8 h, and 1 received 40 mg/kg q8 h. Median gestational age at birth and post-natal age were 27 weeks and 18 days, respectively. Median plasma clearance (CL), volume of distribution, and elimination T½ were 0.12 L/kg/h, 0.54 L/kg, and 2.9 h, respectively. A significant, positive association was observed between CL and postconceptional age. All infants had predicted meropenem concentrations above an MIC of 2 µg/mL for > 75% of the dosing interval. No serious adverse events related to meropenem were observed. Meropenem doses of 20 mg/kg q12 h to 40 mg/kg q8 h were well tolerated and produced drug plasma concentrations above an MIC that inhibits most susceptible pathogens.