Postmarketing clinical study on cefozopran in comparison with ceftazidime for lower respiratory tract infection

Abstract

To demonstrate the rapid therapeutic effect of cefozopran (CZOP), an injectable cephalosporin antibacterial agent, we conducted a postmarketing comparative study in patients with lower respiratory tract infections, using ceftazidime (CAZ) as a control. Patients were given CZOP and CAZ at a dose of 1g (potency) twice daily for 7 days by intravenous drip infusion. Results were as follows: 1. A total of 412 patients were enrolled in the study, and 376 were included in the full analysis set (FAS). Judgment of clinical efficacy was not possible in 3. Efficacy (proportion of patients showing good responses) was 92.0% (173/188) for the CZOP group and 91.4% (169/185) for the CAZ group, which supported the noninferiority of CZOP to CAZ both at the 90% and 95% confidence intervals (two-sided). Stratified by disease, efficacy was 90.9% (120/132) in patients with bacterial pneumonia for the CZOP group and 93.3% (126/135) for the CAZ group. In patients with chronic respiratory infection, it was 94.6% (53/56) for the CZOP group and 86.0% (43/50) for the CAZ group, verifying the noninferiority of CZOP to CAZ both at the 90% and 95% confidence intervals (two-sided). 2. Bacteriological effects were evaluated in 210 patients in whom causative organisms were identified and the presence or absence of bacteria followed up. Eradication (proportion of patients in whom the causative organism was eradicated or replaced with another organism) was 89.5% (94/105) for the CZOP group and 90.5% (95/105) for the CAZ group. No significant difference was seen between groups. Eradication for individual causative organisms was 91.1% (113/124) for the CZOP group and 90.8% (108/119) for the CAZ group, showing no significant difference between groups. Eradication for S. pneumoniae, the most frequently isolated organism, was 100% (42/42) for the CZOP group and 89.5% (34/38) for the CAZ group, indicating a statistically significant difference (p = 0.047). Eradication on day 5 of treatment also favored the CZOP group over the CAZ group statistically significantly (p = 0.049). 3. The aim of therapy was achieved in 52.4% (99/189) of the CZOP group and 50.3% (94/187) of the CAZ group at completion of the study, requiring no additional treatment with antibacterial agents. No statistically significant difference was seen between groups in achieving the aim of therapy. 4. The incidence of adverse symptoms and signs was 3.9% (8/206) in the CZOP group and 5.0% (10/202) in the CAZ group. The incidence of abnormal alterations of laboratory variables was 31.6% (65/206) in the CZOP group and 32.2% (65/202) in the CAZ group. No statistically significant differences were seen between groups. Results indicate that CZOP is not inferior to CAZ in clinical efficacy. They also verified that CZOP has a rapid therapeutic effect in patients with lower respiratory tract infections caused by S. pneumoniae.