International comparative study of cefepime and ceftazidime in the treatment of serious bacterial infections.

In this randomized multicentre study, we compared the safety and efficacy of cefepime, 2.0 g bd i.v., with that of ceftazidime, 2.0 g tid i.v., as initial treatment of adult patients with serious infections of bacterial aetiology. Three hundred and forty-eight patients were entered into the study, 173 received cefepime and 175 ceftazidime. The treatment groups were comparable with respect to demographic characteristics, including the types of infection (cefepime/ceftazidime: urinary tract, 55/72; lower respiratory tract, 83/74; skin and soft tissue, 23/14; septicaemia, 81/81; and others, 15/5). Gram-positive bacteria were identified as pathogens on 86 occasions (cefepime/ceftazidime: 48/41), including 20 Staphylococcus aureus isolates (13/7) and 27 Streptococcus pneumoniae isolates (14/13). Gram-negative bacilli were isolated on 261 occasions (126/135), and included 219 Enterobacteriaceae (cefepime/ceftazidime: 108/111) and 34 strains of Pseudomonas aeruginosa (14/20). An intention-to-treat analysis revealed satisfactory clinical response rates of 80% and 79% for the cefepime and ceftazidime groups, respectively, and bacteriological eradication rates of 85% and 88% for the cefepime and ceftazidime groups, respectively. Of patients with microbiologically documented infections, 86% (84 of 98) treated with cefepime and 87% (94 of 108) treated with ceftazidime responded satisfactorily. Thirty-two patients (19%) treated with cefepime and 26 (15%) treated with ceftazidime died. Thirty-six patients in the cefepime group and 23 in the ceftazidime group experienced adverse events; therapy was discontinued prematurely in four and two patients in the cefepime and ceftazidime groups, respectively. Of the patients experiencing adverse events, 22 (13%) treated with cefepime developed intolerance at the injection site, compared with 11 (6%) treated with ceftazidime (P = 0.045). In conclusion, twice-daily cefepime (2 g bd) is at least as effective as ceftazidime (2 g tid), as initial empirical therapy for serious bacterial infections in non-neutropenic patients.