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Twice- and Thrice-daily Cephalexin Dosing for Staphylococcus aureus Infections in Children

Amanda Gwee1,2,3, Julie Autmizguine4,5,6, Nigel Curtis1,2,3

  • 1From the Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.

The Pediatric Infectious Disease Journal
|May 16, 2020
PubMed
Abstract

Insights

This study developed new dosing schedules for cephalexin in children to treat Staphylococcus aureus infections. Twice-daily and thrice-daily regimens were identified to improve treatment adherence and reduce medication burden.

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Pediatric Infectious Diseases
  • Antibiotic Dosing Optimization

Background:

  • Cephalexin is a common antibiotic for methicillin-susceptible Staphylococcus aureus (MSSA) infections in children.
  • Standard dosing (4 times daily) is often reduced to improve patient adherence.
  • Population pharmacokinetics can inform optimized dosing strategies.

Purpose of the Study:

  • To develop a population pharmacokinetic model for cephalexin in pediatric patients.
  • To determine appropriate twice-daily (BID) and thrice-daily (TID) cephalexin dosing regimens for MSSA infections.
  • To achieve pharmacodynamic targets for effective treatment in children.

Main Methods:

  • Utilized a nonlinear mixed-effects modeling approach for population pharmacokinetics.
  • Data from a prospective pharmacokinetic study in 12 children (1-16 years) with bone and joint infections.
  • Simulations to identify BID and TID regimens ensuring ≥90% of children meet pharmacodynamic targets.

Main Results:

  • A one-compartment model with a transit compartment for oral absorption delay was established.
  • For BID dosing, required doses ranged from 22-45 mg/kg (MIC 1-2 mg/L) to 80 mg/kg (MIC 4 mg/L).
  • For TID dosing, required doses ranged from 15-25 mg/kg (MIC 1-2 mg/L) to 45 mg/kg (MIC 4 mg/L).

Conclusions:

  • Proposed BID and TID cephalexin dosing regimens for prospective evaluation.
  • Reduced dosing frequency can decrease the medication burden for pediatric patients.
  • Optimized dosing can enhance treatment compliance for MSSA infections in children.

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