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

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 .(c) 2022 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )