Therapeutic drug monitoring of meropenem and pharmacokinetic-pharmacodynamic target assessment in critically ill pediatric patients from a prospective observational study

Abstract

Objectives: To compare the unbound plasma meropenem concentrations at mid-dosing intervals (C_mid, 50%fT), end-dosing intervals (C_trough, 100%fT), and proportions of patients achieving 50%fT and 100%fT above minimum inhibitory concentration (MIC) (50%fT_>MIC and 100%fT_>MIC) between extended infusion (EI) and intermittent bolus (IB) administration in a therapeutic drug monitoring (TDM) program in children.

Methods: A prospective observational study was conducted in children aged 1 month to 18 years receiving meropenem every 8 hours by either EI or IB. Meropenem C_mid, C_trough, and proportions of patients achieving 50%fT_>MIC and 100%fT_>MIC were compared.

Results: TDM data from 72 patients with a median age (interquartile range [IQR]) of 12 months (3-37) were used. Meropenem dose was 120 and 60 mg/kg/day in EI and IB groups, respectively. Geometric mean (95% confidence interval [CI]) C_mid of EI versus IB was 17.3 mg/L (13.7-21.8) versus 3.4 mg/L (1.7-6.7) (P <0.001). Geometric mean (95% CI) C_trough of EI versus IB was 2.3 mg/L (1.6-3.4) versus 0.8 mg/L (0.4-1.5) (P=0.005). Greater proportions of patients achieving 50%fT_>MIC and 100%fT_>MIC were observed in the EI group.

Conclusions: A meropenem dose of 20 mg/kg/dose given by IB should not be used in critically ill children, even if they are not suspected of having a central nervous system infection. A dose of 40 mg/kg/dose given by EI resulted in higher C_mid, C_trough, and proportions of patients achieving 50%fT_>MIC and 100%fT_>MIC.

Keywords: Critically ill patients; Extended infusion; Meropenem; Pediatric; Therapeutic drug monitoring.