Cefepime: a fourth-generation parenteral cephalosporin.

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.