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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Pharmacokinetics of meropenem in children with sepsis undergoing extracorporeal life support: A prospective

Yixue Wang1, Zhiping Li2, Weiming Chen1

  • 1PICU of Children's Hospital of Fudan University, Shanghai, China.

Journal of Clinical Pharmacy and Therapeutics
|January 21, 2021
PubMed

Insights

Meropenem dosing in critically ill children receiving extracorporeal life support (ECLS) showed no significant pharmacokinetic changes. Further PK modeling is needed for optimal meropenem dosing regimens during ECLS.

Area of Science:

  • Pediatric critical care medicine
  • Pharmacokinetics and drug metabolism
  • Infectious diseases

Background:

  • Meropenem is crucial for severe pediatric bacterial infections.
  • Limited data exists on meropenem pharmacokinetics in pediatric sepsis with extracorporeal life support (ECLS).
  • Continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) are common in critically ill children.

Purpose of the Study:

  • To investigate the pharmacokinetic (PK) parameters of meropenem in children with sepsis receiving ECLS.
  • To compare meropenem PK in children on ECMO, CRRT, or neither.

Main Methods:

  • Prospective observational study in a pediatric intensive care unit.
  • 27 children with sepsis receiving meropenem (20 mg/kg every 8 hours) were enrolled.
  • Plasma meropenem concentrations were measured using HPLC-MS/MS; PK parameters were determined by non-compartmental analysis.

Main Results:

  • No significant differences in meropenem PK parameters (t1/2, AUC, CL) were observed between ECMO, CRRT, and no ECLS groups.
  • However, AUC values (AUC_tau and AUC_0-∞) significantly decreased after filtration in the CRRT group.
  • CRRT group showed lower estimated creatinine clearance (eCLCR) than the ECMO group.

Conclusions:

  • Meropenem pharmacokinetics are not significantly altered in pediatric sepsis patients on ECMO and/or CRRT.
  • Further PK modeling studies are recommended to establish optimal meropenem dosing during ECLS.
  • Findings suggest current dosing may be adequate but warrants further investigation for precise regimens.
Abstract

Keywords:
AN69 membranechildrencontinuous renal replacement therapycritically illextracorporeal life supportextracorporeal membrane oxygenationmeropenempharmacokineticsepsis

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