Abstract

We studied meropenem in 23 pre-term (gestational age, 29 to 36 weeks) and 15 full-term (gestational age, 37 to 42 weeks) neonates. Meropenem doses of 10, 20, and 40 mg/kg were administered as single doses (30-min intravenous infusion) on a random basis. Blood was obtained for determining the meropenem concentration nine times. Each child required other antimicrobials for proven/suspected bacterial infections. Samples were assayed by high-performance liquid chromatography analysis. Population pharmacokinetic parameter values were obtained by employing the BigNPAG program. Model building was performed by the likelihood ratio test. The final model included estimated creatinine clearance (CLcr) (Schwartz formula) and weight (Wt) in the calculation of clearance (meropenem clearance = 0.00112 x CLcr + 0.0925 x Wt + 0.156 liter/hr). The overall fit of the model to the data was good (observed = 1.037 x predicted - 0.096; r2 = 0.977). Given the distributions of estimated creatinine clearance and weight between pre-term and full-term neonates, meropenem clearance was substantially higher in the full-term group. A Monte Carlo simulation was performed using the creatinine clearance and weight distributions for pre-term and full-term populations separately, examining 20- and 40-mg/kg doses, 8- and 12-h dosing intervals, and 0.5-h and 4-h infusion times. The 8-h interval produced robust target attainments (both populations). If more resistant organisms were to be treated (MIC of 4 to 8 mg/liter), the 40-mg/kg dose and a prolonged infusion was favored. Treating clinicians need to balance dose choices for optimizing target attainment against potential toxicity. These findings require validation in clinical circumstances.