Low Target Attainment of Intravenous Cefuroxime in Critically Ill Term Neonates and Children: A Pooled Population Pharmacokinetics Study.

BACKGROUND AND

OBJECTIVE

Cefuroxime is a widely prescribed beta-lactam antibiotic, particularly in pediatric cardiac and medical-surgical intensive care units. The aim of this study was to describe intravenous cefuroxime disposition in critically ill pediatric patients. Moreover, target attainment of currently applied dosing regimens was evaluated, and suggestions for improving these dosing regimens were provided.

METHODS

Two datasets were pooled for population pharmacokinetic (popPK) analysis, using NONMEM version 7.5. To assess the optimal target attainment (> 90% of patients with 100% time [T] > [4×] minimal inhibitory concentration [MIC]8mg/L), pharmacokinetic (PK) profiles of different dosage regimens (intermittent/continuous) were simulated using the estimated popPK parameters.

RESULTS

The cohort consisted of 45 pediatric patients with a median (interquartile range [IQR]) age of 391 days [31-3505] and body weight of 9.0 kg [5.0-29.8]. A two-compartment popPK model with first-order elimination and allometric scaling best described cefuroxime disposition. Intravenous cefuroxime clearance was estimated at 5.29 L/h/70 kg. Postnatal age and creatinine clearance (mL/min/1.73 m2) were the best descriptive covariates for the maturation of cefuroxime clearance. Simulations evaluating the current cefuroxime dosing regimens stratified for estimated glomerular filtration rate (eGFR) levels illustrated moderate (< 90%) (eGFR < 30 and 30-80 mL/min/1.73 m2) and poor (< 20%) (eGFR 80-120 and > 120 mL/min/1.73 m2) cefuroxime target attainment across the entire age range. Alternative dosing regimens, including four times daily schedules and continuous infusion, improved target attainment, particularly in older children and those with augmented renal clearance.

CONCLUSIONS

These findings indicate that underexposure due to augmented renal function is possible when applying the current cefuroxime dosing regimens. Future research should focus on individualized dosing strategies to optimize cefuroxime exposure and efficacy in pediatric populations.