Model-informed cefepime dosing in paediatric patients receiving continuous renal replacement therapy

Critically ill children receiving β-lactam antibiotics while on continuous renal replacement therapy (CRRT) are at high risk of subtherapeutic or toxic antibiotic exposures due to patient-specific physiology and CRRT prescription parameters that influence drug pharmacokinetics. This case series describes the use of model-informed precision dosing (MIPD) to guide cefepime therapy in five critically ill paediatric patients receiving CRRT. Individual pharmacokinetic analyses were conducted using measured cefepime plasma concentrations and a previously published population PK model with a mechanistic CRRT module that incorporates CRRT prescription variables, including effluent flow rate, blood flow, and filter type. Residual urine output and CRRT effluent flow rate were found to be strong predictors of intrinsic and extracorporeal clearance, respectively. Across the five cases, CRRT accounted for 26.9% to 83.4% of total cefepime clearance. In three patients, extended infusion was necessary to achieve pharmacodynamic targets for efficacy. No patients required dose reduction to avoid excessive exposure. This series demonstrates the feasibility and clinical utility of bedside pharmacokinetic consultation using MIPD to guide cefepime dosing in paediatric CRRT, accounting for both patient-specific and therapy-related factors.