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Meropenem concentrations in brain tissue of neurointensive care patients exceed CSF levels

Arthur Hosmann1, Lavinia Ritscher1, Heinz Burgmann2

  • 1Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

The Journal of Antimicrobial Chemotherapy
|August 15, 2021
PubMed
Abstract

Insights

Meropenem concentrations in brain tissue exceed those in cerebrospinal fluid (CSF), indicating better drug penetration beyond the blood-brain barrier. CSF levels underestimate meropenem

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Neurocritical Care
  • Infectious Diseases

Background:

  • Inadequate antibiotic exposure in cerebral infections can negatively impact patient outcomes.
  • Cerebrospinal fluid (CSF) antibiotic concentrations are commonly used to estimate drug levels in the brain.
  • The actual unbound, pharmacologically active drug concentration beyond the blood-brain barrier remains largely unknown.

Purpose of the Study:

  • To compare meropenem concentrations in plasma, CSF, and brain tissue microdialysate in neurocritical care patients.
  • To determine the penetration and efficacy of meropenem in the brain parenchyma.

Main Methods:

  • Meropenem concentrations were measured in blood, CSF, and brain tissue microdialysate in 12 patients with subarachnoid hemorrhage receiving 2000 mg every 8 hours.
  • Measurements were taken at steady state (n=11) and after single-dose administration (n=5).
  • Pharmacokinetic parameters, including area under the concentration-time curve (AUC), were calculated.

Main Results:

  • At steady state, free AUC0-8 in brain tissue (26.6 mg·h/L) was over three times higher than in CSF (7.8 mg·h/L).
  • The brain tissue to plasma penetration ratio (0.11) was significantly higher than the CSF to plasma ratio (0.03).
  • Bactericidal concentrations were achieved in plasma and brain tissue for MIC values ≤16 mg/L, but only for MIC values ≤1 mg/L in CSF.

Conclusions:

  • Meropenem achieves adequate bactericidal concentrations in both plasma and brain tissue, even in non-inflamed brain tissue.
  • Cerebrospinal fluid (CSF) concentrations significantly underestimate meropenem's target site activity beyond the blood-brain barrier.
  • Direct measurement of drug concentrations in brain tissue is crucial for optimizing antibiotic therapy in cerebral infections.

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