Vol.53 No.9 September 2005
Postmarketing clinical study on cefozopran in comparison with ceftazidime for lower respiratory tract infection
1)Department of Internal Medicine, Tane General Hospital, 1-2-31 Sakaigawa, Nishi-ku Osaka, Japan
2)First Department of Internal Medicine, Kyorin University, School of Medicine and Affiliated Hospitals
3)First Department of Internal Medicine, Asahikawa Medical College and Affiliated Hospitals
4)Division of Respiratory Diseases, National Hospital Organization Hakodate National Hospital
5)First Department of Internal Medicine, Obihiro Kosei General Hospital
6)Department of Internal Medicine, Mito Kyodo General Hospital
7)Third Department of Internal Medicine, Iwate Medical University and Affiliated Hospitals
8)Department of Respiratory Medicine, Devision of Cancer Control,
Institute of Development, Aging and Cancer, Tohoku University and Affiliated Hospital
9)Department of Internal Medicine, Sendai Kosei Hospital
10)Division of Respiratory Diseases, Department of Internal Medicine, Aizu Sogo Hospital
11)Department of Internal Medicine, Suibarago Hospital
12)Department of Internal Medicine, Shinrakuen Hospital
13)Division of Respiratory Diseases, National Hospital Organization Nishi-Niigata Chuo National Hospital
14)Department of Internal Medicine, Takaoka Hospital
15)Division of Respiratory Diseases, Toranomon Hospital
16)Department of Internal Medicine, Doai Memorial Hospital
17)Department of Internal Medicine, Tokyo Kyosai Hospital
18)Second Department of Internal Medicine, Jikei University, School of Medicine and Affiliated Hospitals
19)Division of Respiratory Diseases, Department of Internal Medicine, Mishuku Hospital
20)Department of Internal Medicine, St. Luke's International Hospital
21)Division of Respiratory Diseases, Showa General Hospital
22)Division of Respiratory Diseases, National Hospital Organization Tokyo National Hospital
23)Division of Respiratory Diseases, Department of Internal Medicine, Kitasato Institute Hospital
24)Institute of Medical Science, St. Marianna University, School of Medicine
25)Department of Internal Medicine, Toyoko Hospital for St. Marianna University, School of Medicine
26)Division of Respiratory Diseases, Department of Internal Medicine, Yokohama City Seibu Hospital for St. Marianna University, School of Medicine
27)Department of Internal Medicine, Kanagawa Prefectural Nursing and Hygienic School Hospital
28)Division of Respiratory Diseases, Kanagawa Cardiovascular and Respiratory Center
29)First Department of Internal Medicine, Yokohama City University, School of Medicine
30)Division of Respiratory Diseases, Department of Internal Medicine, Kanto Rosai Hospital
31)Division of Respiratory Diseases, Department of Internal Medicine, Seirei Mikatahara Hospital
32)Division of Respiratory Diseases, Kosai Joint General Hospital
33)Fourth Department of Internal Medicine, Higashi Municipal Hospital of Nagoya
34)Division of Respiratory Diseases, Nagoya Ekisaikai Hospital
35)Division of Respiratory Diseases, Anjo Kosei Hospital
36)Division of Respiratory Diseases, Gifu Municipal Hospital
37)Division of Respiratory Diseases, National Hospital Organization Kyoto Medical Center
38)Department of Internal Medicine, Kansai Medical University Rakusai New Town Hospital
39)Division of Respiratory Diseases, Department of Allergy Internal Medicine, Kinki University, School of Medicine
40)Division of Respiratory Diseases, Sakai Hospital Kinki University
41)Department of Internal Medicine, Kaizuka Municipal Hospital
42)Division of Respiratory Diseases, Osaka Police Hospital
43)Department of Internal Medicine, Osaka Prefectural Sogo Medical Center
44)Department of Internal Medicine, Osaka Hospital Affiliated with Osaka Office of Society for Prevention of Tuberculosis
45)Second Department of Internal Medicine, Nara Medical University
46)Department of Internal Medicine, Nara Prefectural Hospital
47)Division of Respiratory Diseases, Department of Internal Medicine, Tenri Yorozu Soudansho Hospital
48)Division of Respiratory Diseases, Department of Internal Medicine, Kawasaki Medical School
49)Department of Internal Medicine, Kawasaki Medical School, Kawasaki Hospital
50)Division of Respiratory Diseases, University of Occupational and Environment Health
51)First Department of Internal Medicine, Kyushu University, School of Medicine
52)Division of Respiratory Diseases, National Hospital Organization Fukuoka Higashi Medical Center
53)Department of Internal Medicine, Sawara Hospital/Department of Internal Medicine, Saku Hospital
54)Second Department of Internal Medicine, Fukuoka University, School of Medicine
55)First Department of Internal Medicine, Kurume University, School of Medicine and Affiliated Hospitals
56)Department of Internal Medicine, National Hospital Organization Omuta National Hospital
57)Second Department of Internal Medicine, Nagasaki University, School of Medicine and Affiliated Hospitals
58)Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University and Affiliated Hospitals
59)Second Department of Internal Medicine, Oita University Faculty of Medicine and Affiliated Hospitals
60)First Department of Internal Medicine, Faculty of Medicine, University of The Ryukyus and Affiliated Hospitals
61)Department of Medical Welfare, Kawasaki Medical Welfare University
62)Hamamatsu Institute of Clinical Pharmacology and Therapeutics
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.
Key word
cefozopran, ceftazidime, lower respiratory tract infection, therapeutic effect, post-marketing clinical study
Received
June 30, 2005
Accepted
August 19, 2005
Jpn. J. Chemother. 53 (9): 526-556, 2005