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Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in

Sebastian G Wicha1, Christina Kinast2, Max Münchow1

  • 1Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.

Antimicrobial Agents and Chemotherapy
|July 31, 2024
PubMed

Insights

Continuous meropenem infusion (CI) did not improve cerebrospinal fluid (CSF) penetration or concentrations compared to intermittent infusion (II) in critically ill patients. Meropenem CSF exposure remains highly variable regardless of administration method.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Meropenem penetration into cerebrospinal fluid (CSF) shows high variability, impacting treatment effectiveness.
  • Continuous infusion (CI) of meropenem has been proposed to optimize CSF exposure.
  • Understanding meropenem pharmacokinetics in CSF is crucial for treating CNS infections.

Purpose of the Study:

  • To compare meropenem concentrations and pharmacokinetics in CSF between intermittent infusion (II) and CI.
  • To evaluate the probability of target attainment (PTA) in CSF for both infusion methods.
  • To investigate factors influencing meropenem penetration into the CSF.

Main Methods:

  • Prospective, observational study (NCT04426383) in critically ill patients with external ventricular drains.
  • Population pharmacokinetic modeling (NONMEM 7.5) of meropenem in plasma and CSF.
  • Comparison of CSF concentration-time profiles and PTA between II and CI groups.

Main Results:

  • Meropenem CSF penetration (partition coefficient) was low (6.0%) with substantial inter-individual variability (84.0% CV).
  • Infusion mode (II vs. CI) did not correlate with CSF penetration.
  • CSF interleukin-6 levels positively correlated with meropenem CSF penetration (P < 0.001).

Conclusions:

  • Continuous infusion did not enhance meropenem penetration or concentrations in CSF compared to intermittent infusion.
  • Meropenem exposure in CSF is highly variable and not significantly improved by CI.
  • Further strategies may be needed to optimize meropenem therapy for CNS infections.
Keywords:
central nervous system infectionexternal ventricular drainmeningitispopulation pharmacokineticssepsisventriculitis

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