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Greater optimisation of pharmacokinetic/pharmacodynamic parameters through a loading dose of intravenous colistin in

Noppadol Wacharachaisurapol1, Chayapa Phasomsap2, Warumphon Sukkummee3

  • 1Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

International Journal of Antimicrobial Agents
|March 18, 2020
PubMed

Insights

A colistin loading dose in children with multidrug-resistant Gram-negative bacteria infections improves drug exposure and is safe. This approach is recommended for better treatment outcomes in pediatric patients.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Pediatrics

Background:

  • Rising incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) necessitates effective treatments in children.
  • Colistin is increasingly used, but optimal dosing in pediatric populations requires further investigation.
  • Adult guidelines recommend a colistin loading dose to rapidly achieve therapeutic concentrations.

Purpose of the Study:

  • To compare the pharmacokinetic (PK) parameters of a colistin loading dose versus a standard initial dose in pediatric patients.
  • To evaluate the safety of a colistin loading dose, specifically monitoring for acute kidney injury (AKI).

Main Methods:

  • Prospective, open-label PK study in 20 pediatric patients (2-18 years) with normal renal function.
  • Patients received either a colistin loading dose (LD group) or a standard initial dose (NLD group) of colistimethate sodium (CMS).
  • Plasma colistin concentrations were measured using LC-MS/MS, and PK parameters were analyzed. AKI was monitored via serum creatinine and urine NGAL.

Main Results:

  • The loading dose (LD) group showed higher Cmax (6.1 vs. 4.1 mg/L) and AUC0-t (26.5 vs. 13.5 mg/L·h) compared to the standard dose (NLD) group.
  • Volume of distribution (Vd) and half-life (t1/2) were comparable between groups (LD: 0.7 L/kg, 2.9 h; NLD: 0.6 L/kg, 2.6 h).
  • No patients developed AKI based on serum creatinine criteria, indicating a favorable safety profile for the loading dose.

Conclusions:

  • A CMS loading dose significantly improves colistin exposure in pediatric patients without increasing the risk of AKI.
  • Higher daily CMS doses should be considered for treating pediatric MDR-GNB infections.
  • The findings support the use of a loading dose strategy for colistin in children to achieve therapeutic targets more rapidly.

Keywords:
ColistinMultidrug-resistant bacteriaPaediatricsPharmacodynamicsPharmacokinetics

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