Therapeutic studies of cefepime (BMY 28142) in murine meningitis and pharmacokinetics in neonatal rats

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Abstract
Cefepime (BMY 28142) was compared with ceftazidime, cefotaxime, and moxalactam for efficacy in treating experimental meningitis in mice and neonatal rats. Mice were infected intracranially with Streptococcus pneumoniae, S. agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa and treated intramuscularly. Five- to eight-day-old neonatal rats were injected intracisternally with Haemophilus influenzae, S. pneumoniae, and S. agalactiae and treated intraperitoneally. Cefepime was found to be the most active compound against induced meningitis in mice infected with S. agalactiae. Cefepime was as active as cefotaxime against Staphylococcus aureus meningitis, slightly more active than cefotaxime against S. pneumoniae and E. coli, and as active as ceftazidime against K. pneumoniae and P. aeruginosa meningitis. Cefepime was found to be the most active compound against S. pneumoniae and S. agalactiae meningitis in neonatal rats. Against H. influenzae, cefepime was as active as moxalactam and cefotaxime. Ceftazidime was the least active compound. The pharmacokinetics of cefepime in neonatal rats were similar to those of ceftazidime. Both compounds penetrated well into cerebrospinal fluid and brain tissues of uninfected neonatal rats. Relative concentrations were twice as high as those of cefotaxime and moxalactam.