Vol.53 No.9 September 2005

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

Fumio Miki¹⁾, Hiroyuki Kobayashi²⁾, Naruhiko Sugihara²⁾, Hiroaki Takeda²⁾, Yoshinori Nakazato²⁾, Hiroshi Sugiura²⁾, Susumu Sakayori²⁾, Eiichiro Sakagawa²⁾, Yoshinobu Ohsaki³⁾, Shinobu Osanai³⁾, Hiroshi Ide³⁾, Yutaka Nishigaki³⁾, Tadakatsu Tsuji³⁾, Hiroyuki Matsumoto³⁾, Yasuhiro Yamazaki³⁾, Yuka Fujita³⁾, Shoko Nakao³⁾, Masaaki Takahashi³⁾, Eri Toyoshima³⁾, Shuji Yamaguchi³⁾, Akira Shida⁴⁾, Nao Odajima⁴⁾, Takashi Yoshikawa⁵⁾, Kenshi Aoki⁵⁾, Mariko Ozasa⁵⁾, Ken Osonoi⁶⁾, Meishun Boku⁶⁾, Hiroshi Inoue⁷⁾, Shigeru Sakurai⁷⁾, Harukata Ito⁷⁾, Takashi Mohri⁷⁾, Susumu Takahashi⁷⁾, Chieko Inoue⁷⁾, Kiyokazu Higuchi⁷⁾, Akira Watanabe⁸⁾, Tohru Kikuchi⁸⁾, Hideki Ikeda⁸⁾, Hiroyuki Nakai⁹⁾, Yoshihiro Honda⁹⁾, Satoshi Shoji⁹⁾, Katsunao Niitsuma¹⁰⁾, Yasutoshi Suzuki¹¹⁾, Nobuki Aoki¹²⁾, Kohichi Wada¹³⁾, Katsuhiro Kuwahara¹³⁾, Tetsuji Karino¹⁴⁾, Kazuhiko Shibata¹⁴⁾, Kohichiro Nakata¹⁵⁾, Kohji Narui¹⁵⁾, Yasuyuki Sano¹⁶⁾, Mamoru Ohtomo¹⁶⁾, Naohito Suzuki¹⁶⁾, Masaru Koyama¹⁷⁾, Kohya Shiba¹⁸⁾, Kazuhisa Okada¹⁸⁾, Masakatsu Saji¹⁸⁾, Toshie Akutsu¹⁸⁾, Yoshitaka Nakamori¹⁹⁾, Naohiko Chohnabayashi²⁰⁾, Rokuroh Matsuoka²¹⁾, Hideaki Nagai²²⁾, Yukio Suzuki²³⁾, Wataru Takeshita²³⁾, Jingoroh Shimada²⁴⁾, Kazuo Ishida²⁴⁾, Takemasa Nakagawa²⁵⁾, Masaaki Shibamoto²⁵⁾, Toshio Nakamura²⁶⁾, Yuhko Komase²⁶⁾, Moto-o Arai²⁶⁾, Toshiki Shimada²⁷⁾, Yasushi Nakazawa²⁷⁾, Shigeki Odagiri²⁸⁾, Yuji Watanuki²⁸⁾, Ryuichi Nishihira²⁸⁾, Yoshihiro Hirai²⁸⁾, Makoto Kudoh²⁸⁾, Chikao Suzuki²⁸⁾, Yasuhiro Yoshiike²⁸⁾, Hirotada Ikeda²⁹⁾, Motoyoshi Suzuki²⁹⁾, Masanori Nishikawa²⁹⁾, Kenichi Takahashi²⁹⁾, Kunihiko Ikehara²⁹⁾, Masao Nakamura³⁰⁾, Toshiharu Fuyuki³⁰⁾, Shigeto Takagi³⁰⁾, Kenji Yanase³¹⁾, Kunio Dote³¹⁾, Kazuhide Yamamoto³²⁾, Masahiro Yamakoshi³³⁾, Masashi Yamamoto³⁴⁾, Genshi Itoh³⁴⁾, Kohichiro Shima³⁴⁾, Atsushi Watanabe³⁵⁾, Kohsuke Takahashi³⁵⁾, Yoshiyuki Sawa³⁶⁾, Tsutomu Yoshida³⁶⁾, Hitoshi Asamoto³⁷⁾, Yoshihiro Ueda³⁸⁾, Yoshiko Date³⁸⁾, Yuji Tohta³⁹⁾, Ryuta Haraguchi³⁹⁾, Yukio Nagasaka⁴⁰⁾, Yasuhiro Ieda⁴⁰⁾, Shohei Yasuda⁴⁰⁾, Motokazu Katoh⁴¹⁾, Kiyoshi Komuta⁴²⁾, Yoshiroh Tanio⁴³⁾, Kazuhiro Okano⁴³⁾, Masahiko Takenaka⁴³⁾, Tomiya Masuno⁴⁴⁾, Kazuo Nishii⁴⁴⁾, Nobuhiro Narita⁴⁵⁾, Keiichi Mikasa⁴⁵⁾, Mitsuru Konishi⁴⁵⁾, Kohichi Maeda⁴⁵⁾, Yuuichi Takezawa⁴⁶⁾, Wataru Mori⁴⁶⁾, Yoshiroh Kai⁴⁶⁾, Yuuko Sugimura⁴⁶⁾, Kazukiyo Oida⁴⁷⁾, Tetsuroh Inoue⁴⁷⁾, Kohshi Katoh⁴⁷⁾, Toshiharu Matsushima⁴⁸⁾, Yoshihito Niki⁴⁸⁾, Kohichiroh Yoshida⁴⁸⁾, Jiroh Okimoto⁴⁹⁾, Junichi Nakamura⁴⁹⁾, Hirohide Yoneyama⁴⁹⁾, Yoshihiro Kobashi⁴⁹⁾, Masamitsu Kido⁵⁰⁾, Chiharu Yoshii⁵⁰⁾, Yoshiroh Sawae⁵¹⁾, Kiyoshi Ninomiya⁵²⁾, Yoshiaki Tao⁵²⁾, Masayuki Miyazaki⁵²⁾, Kohji Takagi⁵³⁾, Minoru Yoshida⁵⁴⁾, Kentaroh Watanabe⁵⁴⁾, Kohtaroh Ohizumi⁵⁵⁾, Hisashi Watanabe⁵⁵⁾, Yoshiyuki Mitsutake⁵⁵⁾, Keisuke Takeda⁵⁵⁾, Shinzoh Kawaguchi⁵⁵⁾, Takashi Mitsui⁵⁵⁾, Mitsunobu Nishimoto⁵⁵⁾, Masashi Kawahara⁵⁵⁾, Hideyuki Koga⁵⁵⁾, Shin Nakahara⁵⁵⁾, Masashi Takamoto⁵⁶⁾, Yasuko Harada⁵⁶⁾, Yoshinari Kitahara⁵⁶⁾, Akira Kajiki⁵⁶⁾, Nobuhiko Nagata⁵⁶⁾, Shigeru Kohno⁵⁷⁾, Kazunori Tomono⁵⁷⁾, Shigefumi Maesaki⁵⁷⁾, Katsunori Yanagihara⁵⁷⁾, Yoshitsugu Miyazaki⁵⁷⁾, Kinichi Izumikawa⁵⁷⁾, Yasumasa Dohtsu⁵⁷⁾, Naofumi Suyama⁵⁷⁾, Tohru Ishino⁵⁷⁾, Sumio Kawamura⁵⁷⁾, Hikaru Tanaka⁵⁷⁾, Keiko Iida⁵⁷⁾, Jun Araki⁵⁷⁾, Masami Watanabe⁵⁷⁾, Tsuyoshi Nagatake⁵⁸⁾, Moritoshi Akiyama⁵⁸⁾, Atsushi Takahashi⁵⁸⁾, Masakazu Takasugi⁵⁸⁾, Hironori Masaki⁵⁸⁾, Hirofumi Tanaka⁵⁸⁾, Kenji Kawakami⁵⁸⁾, Yoshiaki Utsunomiya⁵⁸⁾, Yoshiko Tsuchihashi⁵⁸⁾, Kazuhiko Hoshino⁵⁸⁾, Norichika Asoh⁵⁸⁾, Hideki Ikeda⁵⁸⁾, Shohzaburo Onizuka⁵⁸⁾, Shinobu Kobayashi⁵⁸⁾, Hiroshi Watanabe⁵⁸⁾, Masaru Nasu⁵⁹⁾, Issei Tokimatsu⁵⁹⁾, Tohru Yamasaki⁵⁹⁾, Hiroshi Kohno⁵⁹⁾, Shinji Ando⁵⁹⁾, Toshiko Gendo⁵⁹⁾, Tatsuhiko Mieno⁵⁹⁾, Yoshinori Kohhara⁵⁹⁾, Atsushi Saito⁶⁰⁾, Masao Tateyama⁶⁰⁾, Yasukazu Ohyama⁶⁰⁾, Rinzo Soejima (deceased) ⁶¹⁾, and Mitsuyoshi Nakashima⁶²⁾

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