Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

Abstract Objectives Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetics (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children, in order to optimize individual dosing regimens. Methods We included all children (age 2.5 Kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. Data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% f T > 4 × M I C . Results Thirty-nine patients with a median [range] age of 7 [0.1-17] years and a BW of 21 [2.8-79] kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the 2 influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW 200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% f T > 4 × M I C . Conclusions In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % f T > 4 × M I C in children with normal and augmented renal function.