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Cefepime is efficacious against penicillin- and quinolone-resistant pneumococci in experimental meningitis
Philippe Cottagnoud1, Fernando Acosta, Marianne Cottagnoud
1Department of Internal Medicine, Inselspital, 3010 Bern, Switzerland. pcottagn@insel.ch
Abstract:
In experimental rabbit meningitis, cefepime given at a dose of 100 mg/kg was associated with concentrations in the cerebrospinal fluid of between 5.3 and 10 mg/L and a bactericidal activity of -0.61 +/- 0.24 Delta log(10) cfu/mL x h, similar to the standard regimen of ceftriaxone combined with vancomycin (-0.58 +/- 0.14 Delta log(10) cfu/mL x h) in the treatment of meningitis due to a penicillin- and quinolone-resistant pneumococcal mutant strain (MIC 4 mg/L). Compared with the penicillin-resistant parental strain, the penicillin- and quinolone-resistant mutant was killed more slowly by cefepime and ceftriaxone in time-killing assays in vitro over 8 h.
Insights
Cefepime demonstrated comparable bactericidal activity to ceftriaxone plus vancomycin in rabbit meningitis models. However, a resistant pneumococcal strain showed slower killing rates with both antibiotics in vitro.
Area of Science:
- Pharmacology and Microbiology
- Infectious Diseases
- Neuroscience
Background:
- Meningitis treatment often involves antibiotics like ceftriaxone and vancomycin.
- Emergence of antibiotic resistance in pathogens like Streptococcus pneumoniae poses a significant clinical challenge.
- Cefepime is a broad-spectrum cephalosporin with potential utility in central nervous system infections.
Purpose of the Study:
- To evaluate the efficacy of cefepime in experimental rabbit meningitis.
- To compare cefepime's cerebrospinal fluid (CSF) concentrations and bactericidal activity against ceftriaxone plus vancomycin.
- To assess the in vitro activity of cefepime and ceftriaxone against penicillin- and quinolone-resistant Streptococcus pneumoniae strains.
Main Methods:
- Experimental rabbit meningitis model was utilized.
- Cerebrospinal fluid (CSF) concentrations and bactericidal activity of cefepime (100 mg/kg) were measured.
- In vitro time-killing assays were performed using cefepime and ceftriaxone against resistant pneumococcal strains.
Main Results:
- Cefepime achieved CSF concentrations of 5.3–10 mg/L with bactericidal activity (-0.61 ± 0.24 Delta log(10) cfu/mL x h) comparable to ceftriaxone plus vancomycin (-0.58 ± 0.14 Delta log(10) cfu/mL x h).
- The penicillin- and quinolone-resistant pneumococcal mutant strain (MIC 4 mg/L) was treated effectively.
- In vitro, cefepime and ceftriaxone exhibited slower killing of the resistant mutant compared to the susceptible parental strain over 8 hours.
Conclusions:
- Cefepime shows promising therapeutic potential for meningitis caused by resistant pneumococcal strains, exhibiting comparable efficacy to standard regimens in vivo.
- Antibiotic resistance significantly impacts bacterial killing rates, highlighting the need for careful drug selection and monitoring.
- Further research is warranted to fully elucidate cefepime's role in treating complex meningitis cases.