Cefepime: a new fourth-generation cephalosporin

The chemistry, pharmacology, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, and dosage of cefepime are reviewed. Fourth-generation cephalosporins, such as cefepime, have a quaternary nitrogen that is positively charged at the 3-position, providing the properties of a zwitterion. A 2-aminothiazolyl-acetamido group in the side chain at the 7-position with an alpha-oxyimino substitution may enhance stability against beta-lactamases by preventing the enzymes' approach to the main nucleus. Cefepime may exert its antimicrobial effect by attaching to specific penicillin-binding proteins, disrupting cell-wall synthesis. Cefepime has good activity against gram-positive organisms, such as Staphylococcus aureus, and gram-negative organisms, such as Pseudomonas aeruginosa. Cefepime is not active in vitro against Enterococcus faecalis, Clostridium difficile, and methicillin- and cefazolin-resistant Staph. aureus. Cefepime's activity against gram-negative organisms is similar to that of most third-generation cephalosporins. The agent has poor activity against Bacteroides species. The most common mechanism of resistance to cefepime is the excess production of beta-lactamases. Maximum peak plasma concentrations are two to three times higher after i.v. administration than after intramuscular administration. In healthy adults, the volume of distribution is 13-22 L and the elimination half-life is 2-2.3 hours. Clinical studies show that cefepime is as effective as cefotaxime or ceftazidime in patients with infections of the lower respiratory tract, skin and skin structures, urinary tract, or female reproductive system. Cefepime reduces fever as effectively as ceftazidime or piperacillin plus gentamicin in neutropenic patients. The most common adverse effects of cefepime are headache (2.4%), nausea (1.8%), rash (1.8%), and diarrhea (1.7%). Depending on creatinine clearance, the dosage of cefepime is 1000-2000 mg i.v. every 8-24 hours for life-threatening infections and 500-2000 mg i.v. every 12-24 hours for severe infections. Cefepime's clinical efficacy is comparable to that of ceftazidime and cefotaxime.