Population Pharmacokinetics and Pharmacodynamic Implementation of Meropenem in Critically Ill Pediatric Patients.

This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM. Individual PK parameters were determined by a two-compartment analysis. The median (range) age and body weight were 1.4 (0.03-14.6) years old and 8.9 (2.7-40.9) kg, respectively, and eight (23.5%) patients received continuous renal replacement therapy (CRRT), of which three received extracorporeal membrane oxygenation. Renal function, systemic inflammatory response syndrome (SIRS) score, and the use of CRRT for central volumes of distribution (Vc) were identified as significant covariates. The mean clearance (CL), Vc, and peripheral volume of distribution (Vp) were 0.45 l/kg/h, 0.49 l/kg, and 0.34 l/kg, respectively. The mean population CL of MEM increased by 35% in patients with SIRS and Vc increased by 66% in patients on CRRT in the final model. Dosing simulations suggested that the standard dosing regimen provided insufficient PD exposures of 100% free time above the minimum inhibitory concentration, and higher doses (40-80 mg/kg/dose every 8 h) with a prolonged 3-h infusion were required to ensure the appropriate PD exposures for patients with SIRS. Our PK model indicated that critically ill pediatric patients are at risk of subtherapeutic exposure under the standard dosing regimen of MEM. A larger, prospective investigation confirming the safety and efficacy of higher concentrations and prolonged infusion of MEM is necessary.