Therapeutic drug monitoring of meropenem and pharmacokinetic-pharmacodynamic target assessment in critically ill pediatric patients from a prospective observational study
Passara Maimongkol, Wanlika Yonwises, Suvaporn Anugulruengkitt, Jiratchaya Sophonphan, Wanchai Treyaprasert, Noppadol Wacharachaisurapol
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 .