Cefepime is efficacious against penicillin- and quinolone-resistant pneumococci in experimental meningitis

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A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
09:17

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii

Published on: January 2, 2017

Philippe Cottagnoud1, Fernando Acosta, Marianne Cottagnoud

  • 1Department of Internal Medicine, Inselspital, 3010 Bern, Switzerland. pcottagn@insel.ch

The Journal of Antimicrobial Chemotherapy
|January 30, 2002
PubMed

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.

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