Cefepime: A Fourth-Generation Parenteral Cephalosporin

Abstract

OBJECTIVE: To review the chemistry, microbiology, pharmacokinetics, therapeutic efficacy, adverse effect profile, drug interactions, dosing, and administration of cefepime, a new fourth-generation parenteral cephalosporin. DATA SOURCES: A MEDLINE search of the available literature, including clinical trials and reviews, was performed. Abstracts presented at recent scientific conferences and current publications were also reviewed. DATA SELECTION: In vitro and preclinical data were included, as well as data from Phase II and III clinical trials. DATA SYNTHESIS: Cefepime is an extended-spectrum parenteral cephalosporin antibiotic active in vitro against a broad spectrum of gram-positive and gram-negative aerobic bacteria. The gram-positive spectrum is similar to that of cefotaxime, the gram-negative spectrum is similar to that of ceftazidime, and many, though not all, organisms resistant to these two agents remain susceptible to cefepime, prompting the fourth-generation designation. Cefepime has a high affinity for penicillin-binding proteins and, due to its zwitterionic configuration, rapidly penetrates outer-membrane porin channels of bacteria. Beta-lactamases appear to have a low affinity for the drug. Cefepime has a decreased propensity to induce beta-lactamases compared with other beta-lactam antibiotics. Cefepime has a pharmacokinetic disposition similar to that of other renally eliminated cephalosporins, with a half-life of approximately 2 hours. Cefepime has demonstrated clinical efficacy against a variety of infections, including urinary tract infections, pneumonia, and skin and skin structure infections. Cefepime is generally well tolerated. CONCLUSIONS: Cefepime may have several chemical and pharmacologic advantages over currently available third-generation cephalosporins. In vitro data indicate that cefepime retains activity against some, but not all, gram-negative bacteria resistant to third-generation cephalosporins; however, clinical efficacy against infections due to resistant pathogens remains to be established. Cefepime was at least as effective as comparators during clinical trials, and may prove to be a viable alternative to other currently available agents.