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Optimized Dosing Regimens of Meropenem in Septic Children Receiving Extracorporeal Life Support

Yixue Wang1, Weiming Chen1, Yidie Huang2

  • 1Department of Pediatric Critical Care Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Frontiers in Pharmacology
|September 10, 2021
PubMed

Insights

Optimized meropenem dosing for pediatric sepsis patients on extracorporeal life support (ECLS) improves treatment outcomes. Recommended regimens ensure higher probability of target attainment (PTA) for effective bacterial killing.

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Pediatric Critical Care
  • Infectious Diseases

Background:

  • Sepsis in children receiving extracorporeal life support (ECLS) presents unique pharmacokinetic challenges.
  • Meropenem dosing requires optimization to ensure therapeutic efficacy in this vulnerable population.
  • Understanding meropenem population pharmacokinetics is crucial for effective sepsis management during ECLS.

Purpose of the Study:

  • To develop a population pharmacokinetic (PK) model for meropenem in pediatric sepsis patients undergoing ECLS.
  • To optimize meropenem dosage regimens using probability of target attainment (PTA) analysis.
  • To provide evidence-based dosing recommendations for improved clinical outcomes.

Main Methods:

  • Prospective enrollment of 25 pediatric sepsis patients receiving ECLS.
  • Nonlinear mixed-effects modeling (NONMEM) used to analyze meropenem concentration-time data.
  • Stochastic simulations conducted to calculate PTA and optimize dosage regimens.

Main Results:

  • Bodyweight and creatinine clearance significantly impacted meropenem PK parameters; ECLS itself did not.
  • Current 40 mg/kg q8h (3-h infusion) achieved only 77.4% PTA for 100%T > MIC target.
  • A 40 mg/kg q8h (1-h infusion) dose is necessary for 50%T > MIC target against bacteria with MIC 2 mg/L.

Conclusions:

  • The developed population PK model accurately describes meropenem disposition in pediatric sepsis patients on ECLS.
  • Optimized dosing regimens are recommended based on PTA for both 50%T > MIC and 100%T > MIC targets.
  • Recommendations consider patient weight, estimated creatinine clearance, and bacterial MIC for tailored therapy.

Keywords:
childrencontinuous renal replacement therapyestimated creatinine clearanceeven extracorporeal membrane oxygenationmeropenempharmacokinetics/pharmacodynamicssepsistarget attainment

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