The in vitro activity of cefepime was compared with that of amikacin, ceftazidime, imipenem, ciprofloxacin, and piperacillin-tazobactam by using the E-test against five groups of carefully selected organisms: Klebsiella pneumoniae (68 isololates), Pseudomonas aeruginosa (62), methicillin-susceptible Staphylococcus aureus (MSSA) (60), and two groups of Enterobacteriaceae (60 and 62 isolates, respectively). The bacteria were subdivided according to whether the infection was nosocomial or community-acquired, applying accepted and predefined criteria. These isolates were obtained from patients admitted to our medical center throughout 1998. We retrospectively compared antimicrobial susceptibilities of the study sample with those of the +/- 3000 bacterial strains isolated from blood stream infections since 1990: the study sample appeared to represent adequately the clinical databank. Presence of extended-spectrum beta-lactamase (ESBL) was determined in all groups of Enterobacteriaceae with the ESBL screening E-test strip. Of the 252 Gram-negative bacilli tested, 242 (96%) were susceptible to cefepime, whereas only 168 (67%) were susceptible to ceftazidime, 211 (84%) to amikacin, and 220 (87%) to piperacillin-tazobactam (p < 0.001). Imipenem was slightly superior to cefepime with only seven isolates resistant (3%), six of which were P. aeruginosa. Cefepime was more active against Enterobacteriaceae than ceftazidime (93% vs. 72%, p < 0.001). This superiority was most evident against nosocomial strains of K. pneumoniae, against which cefepime was > three times more active than ceftazidime. The high level of resistance seen in nosocomial isolates of K. pneumoniae is consistent with high rates of ESBL production (69%, compared with 15-26% in other Enterobacteriaceae). The MIC90 of cefepime to methicillin-sensitive S. aureus was 1.5 micrograms/mL, whereas that of ceftazidime was 4 micrograms/mL; the susceptibility rate of both was 100%. In conclusion, cefepime possesses in vitro potencies against MSSA and current clinical strains of Gram-negative bacilli, many of which harbor resistance to other antimicrobial agents. Hence, it seems very suitable for empiric coverage of serious nosocomial infections.