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Dose recommendations for intravenous colistin in pediatric patients from a prospective, multicenter, population

Noppadol Wacharachaisurapol1, Warumphon Sukkummee1, Orawan Anunsittichai2

  • 1Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases
|June 30, 2021
PubMed

Insights

This study on pediatric colistin pharmacokinetics found serum creatinine significantly impacts drug clearance. Optimal dosing requires adjusting colistin dosage based on individual creatinine levels and target concentrations.

Area of Science:

  • Pharmacology
  • Pediatric Infectious Diseases
  • Clinical Pharmacy

Background:

  • Intravenous colistin is crucial for treating multidrug-resistant Gram-negative infections in children.
  • Understanding colistin population pharmacokinetics (PPK) in pediatric populations is essential for optimizing therapeutic outcomes.
  • Current dosing guidelines may not adequately account for pediatric-specific pharmacokinetic variability.

Purpose of the Study:

  • To characterize the population pharmacokinetics of intravenous colistin in pediatric patients.
  • To propose optimized colistin dosage regimens for children based on pharmacokinetic modeling.
  • To evaluate the probability of achieving target colistin plasma concentrations in pediatric populations.

Main Methods:

  • A prospective, multicenter population pharmacokinetic (PPK) study.
  • Utilized Phoenix 64 software (version 8.3) for PPK analysis.
  • Performed simulations to assess target attainment probability for average steady-state concentrations (Css,avg).

Main Results:

  • Analyzed 334 colistin concentrations from 79 pediatric patients (median age 2.6 years).
  • A one-compartment model with first-order elimination was identified, with serum creatinine (SCr) as a significant covariate for colistin clearance.
  • Simulations indicated the standard 5 mg CBA/kg/day dose achieved target Css,avg (2 mg/L) in only 18.2-63.0% of patients.

Conclusions:

  • Serum creatinine is a key determinant of colistin clearance in pediatric patients.
  • Colistin dosing strategies must be individualized based on patient SCr levels.
  • Tailoring dosage to SCr and desired Css,avg is critical for effective pediatric colistin therapy.
Abstract

Keywords:
ColistinMultidrug-resistant bacteriaPediatricsPharmacokinetics

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