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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus

Fiorenza Ferrari1,2, Paola Milla3, Marco Sartori1

  • 1Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Azienda ULSS 8 Berica, Vicenza, Italy.

Clinical Pharmacokinetics
|August 5, 2024
PubMed
Abstract

Insights

Medium cut-off (MCO) membranes show comparable removal of piperacillin, tazobactam, and meropenem compared to high-flux membranes (HFM) during renal replacement therapy. This study found similar antibiotic plasma levels regardless of the membrane type used.

Area of Science:

  • Nephrology
  • Pharmacokinetics
  • Critical Care Medicine

Background:

  • Renal replacement therapy (RRT) is crucial for removing low-molecular-weight, hydrophilic drugs.
  • Medium cut-off (MCO) membranes enhance middle molecule removal by increasing the cut-off from 30 to 45 kDa.
  • New dialysis technologies like MCO membranes warrant evaluation for antimicrobial drug clearance.

Purpose of the Study:

  • To compare the antimicrobial removal efficacy of MCO membranes versus standard high-flux membranes (HFM).
  • To evaluate the impact of continuous hemodialysis with MCO membranes (MCO-CVVHD) versus HFM-CVVHDF on piperacillin, tazobactam, and meropenem removal.
  • To assess antibiotic plasma levels and treatment efficiency with both membrane types.

Main Methods:

  • A monocentric randomized crossover pilot study involving 20 patients.
  • Patients underwent both MCO-CVVHD and HFM-CVVHDF treatments in a randomized sequence.
  • Key metrics included extraction ratio (ER), effluent clearance (Cleff), and nadir plasma antibiotic levels.

Main Results:

  • High-flux membrane hemodialysis (HFM-CVVHDF) demonstrated greater ER and Cleff for meropenem and tazobactam compared to MCO-CVVHD.
  • No significant differences were observed in nadir plasma concentrations or overall treatment efficiency between the two membrane types.
  • Piperacillin and tazobactam showed lower nadir plasma concentrations on the second treatment day, irrespective of the filter type used.

Conclusions:

  • Medium cut-off (MCO) membranes provide comparable in vivo removal of piperacillin, tazobactam, and meropenem to high-flux membranes (HFM).
  • The findings suggest MCO membranes are a viable alternative for antibiotic management during RRT.
  • Further research may explore the clinical implications of these findings in diverse patient populations.

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