Cerebrospinal fluid impairs antimicrobial activity of fosfomycin in vitro

Robert Sauermann1, Richard Schwameis, Manfred Fille

  • 1Department of Clinical Pharmacology, Section of Molecular Pharmacokinetics and Imaging, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. robert.sauermann@meduniwien.ac.at

Abstract

Insights

Fosfomycin

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Microbiology

Background:

  • Fosfomycin demonstrates good penetration into cerebrospinal fluid (CSF), making it a candidate for treating central nervous system (CNS) infections.
  • Understanding the drug's activity within the CNS environment is crucial for effective treatment.

Purpose of the Study:

  • To evaluate how human cerebrospinal fluid (CSF) affects the antimicrobial efficacy of fosfomycin.
  • To compare fosfomycin's activity in CSF versus standard laboratory media.

Main Methods:

  • Time-kill kinetics were assessed for Staphylococcus aureus in Mueller-Hinton broth (MHB) and human CSF across various fosfomycin concentrations (0.25x to 8x MIC).
  • In vitro simulations replicated a patient's in vivo CSF pharmacokinetic profile to assess bacterial response.

Main Results:

  • Higher fosfomycin concentrations (8x MIC) were needed for sustained bacterial killing in CSF compared to MHB (1x MIC).
  • Simulated CSF drug concentrations led to initial bacterial killing but were followed by bacterial regrowth, indicating insufficient sustained activity.

Conclusions:

  • Fosfomycin exhibits reduced antimicrobial activity in human CSF compared to standard MHB.
  • Fosfomycin doses that only slightly exceed the minimum inhibitory concentration (MIC) may be inadequate for achieving bactericidal effects in CNS infections.

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