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

Clin Microbiol Infect. 2021 Mar;27(3):413-419. doi: 10.1016/j.cmi.2020.04.022. Epub 2020 Apr 29.


Objectives: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (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 < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC.

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 two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC.

Conclusions: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

Keywords: Augmented renal clearance; Cephalosporin; MSSA; Paediatric intensive care unit; Pharmacokinetics; β-lactam.

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Cefazolin / blood
  • Cefazolin / pharmacokinetics*
  • Cefazolin / therapeutic use*
  • Child
  • Child, Preschool
  • Critical Illness
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Male
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects*


  • Anti-Bacterial Agents
  • Cefazolin