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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

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

E Salvador1, M Oualha1, E Bille2

  • 1Department of Paediatric Intensive Care Unit, Necker Enfants Malades Hospital, Paris Descartes University, Sorbonne-Paris Cité, 149 Rue de Sèvres, 75015, Paris, France; Pharmacology and Drug Evaluation in Children and Pregnant Women EA7323, Paris Descartes University, 27 Rue Du Faubourg Saint Jacques, 75014, Paris, France.

Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
|May 4, 2020
PubMed

Insights

Continuous cefazolin infusion optimizes dosing for critically ill children with methicillin-sensitive Staphylococcus aureus (MSSA) infections. This approach ensures effective drug exposure, crucial for achieving therapeutic targets in pediatric patients.

Area of Science:

  • Pharmacology
  • Pediatric Infectious Diseases
  • Critical Care Medicine

Background:

  • Cefazolin is a primary treatment for methicillin-sensitive Staphylococcus aureus (MSSA) infections.
  • Growth and critical illness significantly alter pharmacokinetic (PK) parameters in children.
  • Optimizing cefazolin dosing is essential for effective treatment in critically ill pediatric patients.

Purpose of the Study:

  • To develop a population PK model for cefazolin in critically ill children.
  • To optimize cefazolin dosing regimens for MSSA infections in this vulnerable population.

Main Methods:

  • Included critically ill children (<18 years, >2.5 kg BW) with MSSA infections receiving cefazolin.
  • Quantified cefazolin plasma concentrations using high-performance liquid chromatography.
  • Utilized population PK modeling (MONOLIX) and Monte Carlo simulations to achieve target drug exposure (100% fT > 4xMIC).

Main Results:

  • A one-compartment PK model was established for 39 pediatric patients.
  • Body weight (BW) and estimated glomerular filtration rate (eGFR) were key covariates influencing cefazolin clearance.
  • Continuous infusion regimens of 100-150 mg/kg/day were identified as optimal for achieving PK targets.

Conclusions:

  • Continuous cefazolin infusion is the preferred administration route for critically ill children with MSSA.
  • This strategy effectively achieves target drug concentrations across varying renal functions.
  • Optimized dosing regimens are critical for successful treatment outcomes in pediatric critical care.
Abstract

Keywords:
Augmented renal clearanceCephalosporinMSSAPaediatric intensive care unitPharmacokineticsβ-lactam

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