CEFEPIME - A NEW 4TH-GENERATION CEPHALOSPORIN

The chemistry, pharmacology, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, and dosage of cefepime are review ed. Fourth-generation cephalosporins, such as cefepime, have a quatern ary nitrogen that is positively charged at the 3-position, providing t he properties of a zwitterion. A 2-aminothiazolyl-acetamido group in t he side chain at the 7-position with an alpha-oxyimino substitution ma y enhance stability against P-lactamases by preventing the enzymes' ap proach to the main nucleus. Cefepime may exert its antimicrobial effec t by attaching to specific penicillin-binding proteins, disrupting cel l-wall synthesis. Cefepime has good activity against gram-positive org anisms, such as Staphylococcus aureus, and gram-negative-organisms, su ch as Pseudomonas aeruginosa. Cefepime is not active in vitro against Enterococcus faecalis, Clostridium difficile, and methicillin- and cef azolin-resistant Staph. aureus. Cefepime's activity against gram-negat ive organisms is similar to that of most third-generation cephalospori ns. 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 admini stration. 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 a s effectively as ceftazidime or piperacillin plus gentamicin in neutro penic patients. The most common adverse effects of cefepime are headac he (2.4%), nausea (1.8%) rash (1.8%), and diarhea (1.7%). Depending on creatinine clearance, the dosage of cefepime is 1000-2000 mg i.v. eve ry 8-24 hours for life-threatening infections and 500-2000 mg i.v. eve ry 12-24 hours for severe infections. Cefepime's clinical efficacy is comparable to that of ceftazidime and cefotaxime.