Cefepime is a new cephalosporin with an enhanced antibacterial potency and spectrum. More rapid penetration into many gram-negative bacilli, targeting of multiple penicillin-binding proteins, and resistance to inactivation by many beta-lactamases account for its activity against organisms that have developed resistance to agents such as ceftazidime, cefotaxime, or ceftriaxone. This study identified 16 patients with 17 infections due to Enterobacter species organisms with reduced susceptibility or resistance to ceftazidime. Most isolates were multiply resistant to other beta-lactam drugs as well, but all were susceptible to cefepime. All 17 infections, which included pneumonia, urinary tract infection, intraabdominal infection, and bacteremia, responded clinically to intravenous cefepime. In particular, cefepime was successfully used in the management of cases of chronic infection that had responded poorly to repeated therapy with imipenem, aminoglycosides, or ciprofloxacin. Eradication of Enterobacter species organisms occurred at 15 (88.2%) of the 17 sites of infection. No emergence of resistance to cefepime was noted.