Pharmacokinetics and Therapeutic Target Attainment of Meropenem in Pediatric Post-Liver Transplant Patients: Extended vs Intermittent Infusion

Transplant Proc. 2023 Dec;55(10):2456-2461. doi: 10.1016/j.transproceed.2023.09.020. Epub 2023 Nov 2.

Abstract

Purpose: The aim of this study is to characterize the concentration-time profile, pharmacokinetics parameters, and therapeutic target attainment of meropenem in pediatric post-liver transplant patients according to the duration of infusion.

Methods: This is a prospective cohort of pediatric transplant recipients with preserved renal function receiving meropenem 40 mg/kg every 8 hours. The patients were stratified into 2 groups based on infusion duration: G1 (15 minutes of intermittent infusion) and G1 (3 hours of extended infusion). Two blood samples per child were collected during the same interval within 48 hours of starting the antimicrobial. Meropenem concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were assessed using a noncompartmental analysis. The therapeutic target was defined as 100% of the time above the minimum inhibitory concentration.

Findings: Fourteen patients with 28 measured meropenem concentrations were included. Lower values of volume of distribution and meropenem clearance compared with other critically ill pediatric populations were found. All patients achieved the therapeutic target against gram-negative pathogens with a minimum inhibitory concentration of ≤8 mg/L. Patients receiving a 15-minute infusion had higher values of peak and trough concentrations, resulting in unnecessary increased total drug exposure when compared to patients receiving a 3-hour infusion (P < .05).

Conclusions: Meropenem at 120 mg/kg/d attained the therapeutic target against sensitive microorganisms in pediatric liver transplant recipients. The extended infusion should be preferred for patient safety. Because of the pharmacokinetic changes resulting from liver transplantation, individualized meropenem dosing regimens may be necessary.

MeSH terms

  • Anti-Bacterial Agents* / therapeutic use
  • Child
  • Critical Illness / therapy
  • Humans
  • Infusions, Intravenous
  • Liver Transplantation* / adverse effects
  • Meropenem
  • Microbial Sensitivity Tests
  • Prospective Studies
  • Thienamycins / therapeutic use

Substances

  • Meropenem
  • Anti-Bacterial Agents
  • Thienamycins