Fosfomycin penetration into the cerebrospinal fluid of patients with bacterial meningitis
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Abstract:
A comparative study was made of the penetration of fosfomycin, penicillin G, ampicillin and chloramphenicol into the cerebrospinal fluid of patients with meningitis treated with combinations of fosfomycin and one of the other three antibiotics. Minimal inhibitory concentrations and in vitro interaction of these antibiotics against Streptococcus pneumoniae and Neisseria meningitidis strains were determined. 90-96.5% of these strains were sensitive to penicillin G, 95-96.5% to ampicillin, 85-100% to chloramphenicol and 90-100% to fosfomycin. Fosfomycin shows a more marked synergism with penicillin G or ampicillin than with chloramphenicol against both bacterial species. The percentages of penetration into the cerebrospinal fluid were: chloramphenicol, 32%; fosfomycin, 25.7%; ampicillin, 15.9%, and penicillin G, 7.9%. The clinical results show that the combination of fosfomycin + penicillin G or fosfomycin + ampicillin can be an alternative in the treatment of meningitis produced by moderately susceptible strains of S. pneumoniae and N. meningitidis to penicillin G and ampicillin.
Insights
Fosfomycin combined with penicillin G or ampicillin shows promising results for treating meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis, demonstrating good bacterial sensitivity and cerebrospinal fluid penetration.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Meningitis treatment often involves antibiotics with varying cerebrospinal fluid (CSF) penetration.
- Understanding antibiotic interactions and CSF penetration is crucial for optimizing meningitis therapy.
Purpose of the Study:
- To compare the CSF penetration of fosfomycin, penicillin G, ampicillin, and chloramphenicol.
- To evaluate the in vitro synergistic effects of fosfomycin in combination with other antibiotics against meningitis-causing bacteria.
- To assess the clinical utility of fosfomycin combinations for meningitis treatment.
Main Methods:
- Determined minimal inhibitory concentrations (MICs) and in vitro interactions of antibiotics against Streptococcus pneumoniae and Neisseria meningitidis.
- Measured the penetration percentages of antibiotics into the cerebrospinal fluid.
- Analyzed clinical outcomes of patients treated with fosfomycin combinations.
Main Results:
- High sensitivity rates were observed for all tested antibiotics against S. pneumoniae and N. meningitidis.
- Fosfomycin exhibited greater in vitro synergism with penicillin G and ampicillin compared to chloramphenicol.
- CSF penetration percentages: chloramphenicol (32%), fosfomycin (25.7%), ampicillin (15.9%), penicillin G (7.9%).
Conclusions:
- Fosfomycin combined with penicillin G or ampicillin demonstrates potential as an alternative treatment for meningitis.
- This combination is effective against moderately susceptible strains of S. pneumoniae and N. meningitidis.
- Further clinical evaluation of these fosfomycin combinations is warranted.