Clinical evaluation of DQ-2556, a new parenteral cephem antibiotic, and a dose-determination study in complicated urinary tract infections

Sadao Kamidono, Soichi Arakawa, Masuo Yamashita, Shinsuke Takagi, Hideo Oshima, Nobuo Kataoka, Ichiro Nakamura, Takehiro Izumi, Yuji Yamada, Masayuki Sugimoto, Minoru Hazama, Atsushi Sengoku, Yoshiaki Kumamoto, Takaoki Hirose, Yasuhiro Yamaguchi, Yoshikazu Sato, Yoshio Aso, Masaya Oshi, Hiroshi Nito, Nobuo KawamuraHiroaki Inatsuchi, Keishi Okada, Hideaki Hoshino, Motoaki Tanaka, Keizo Suzuki, Yukimichi Kawada, Yoshihito Ban, Yoshito Takahashi, Kanhin Tei, Akihisa Takeda, Hiroyuki Ohmori, Hiromi Kumon, Kazuhiro Hata, Daisuke Yamada, Katsuichi Nanba, Nishitani Mitsuhata Naoki, Joichi Kumazawa, Tetsuro Matsumoto, Noritsugu Shi, Takashi Yoshida, Mitsuru Noguchi, Tetsunori Nakayama, Kazuyuki Sagiyama, Kiyoshi Komatsu, Sanshin Hara, Kenji Itoh, Tetsuo Omoto, Yasuhiro Koikawa, Ken Goto, Takeo Kurozumi, Tetsuo Omoto, Yoshitada Ohi, Motoshi Kawahara, Daishi Yamauchi, Takeshi Shimada, Shinichi Nagata, Tsuneyoshi Kayajima, Akira Imamura, Shizuo Yagi, Nobuya Ogawa, Koichi Deguchi, Nobumasa Kataoka

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Abstract

To evaluate the effectiveness and the safety of DQ-2556, a new parenteral cephem antibiotic, and to find its optimal dose in the treatment of complicated urinary tract infections (UTI) multicenter clinical trials were conducted. Data were summarized according to the criteria of the Japanease UTI committee (the third edition). 1) Open clinical trials DQ-2556 was administered mainly at doses of 0.5g, l.Og and 2.0g twice a day. In the 80 evaluable patients, 32 had excellent, 24 moderate and 24 poor results; the overall efficacy rate was 70.0%. Twice-a-day medication was dose-dependently effective (moderate or excellent):efficacy rates for treatment at doses of 0.5 g b.i.d., 0.g b.i.d. and 2.0g b.i.d. were 59.1% in 22 patients, 73.0% in 37 patients and 80.0% in 10 patients. DQ-2556 was effective in 77.8% of 54 non-indwelling -catheter patients and in 53.8% of 26 indwelling-catheter patients. The overall bacteriological eradication rate was 82.2% (106/129);40 at 49 m-positive bacteria (81.6%) and 66 of 80 gram-negative bacteria (82.5%) were eradicated. Clinical adverse reactions were observed in three in 116 patients (2.6%): a patient vomited severely with nausea three days after the commencement of treatment and another showed mild to moderate eruption. Laboratory adverse reactions were seen in 14 in 109 patients (12.8%); the main findings were abnormalities of liver function represented by elevation of GOT and/or GFT, which were observed in 10 patients. 2) Dose-determination study Complicated UTI without indwelling catheters and also without prostatectomy, i.e., the 3rd, 4 th and 6 th groups were enrolled. The patients were randomly assigned to receive 5-day medication regimens with DQ-2556 at daily dosages of 0.5g b.i.d. (DQ-1.0 group) or l.Og b.i.d. group) and with ceftazidime (CAZ) at daily dosages of l.0g b.i.d. as the control group (CAZ group). The clinical efficacies of these three regimens were compared. Eleven patients in the DQ-1.0 group, 11 in the DQ-2.0 group and 12 in the CAZ group were evaluated. As for background characteristics of the patients, mild renal function failure was seen only in three patients in the DQ -2.0 group, and bacteria with low susceptibility to the compounds were distributed more in the DQ 1.0 and CAZ groups than in the DQ-2.0 group. Except for these characteristics, no significant differences were not found among the three groups. Overall clinical efficacy rates were 100% (11/11) in the DQ-1.0 group, 90.9% (10/11) in the DQ-2.0 group and 83.3% (10/12) in the CAZ group. Bacteriological eradication rates were 100% (12/12) in the DQ-1.0 group, 90.9% (10/11) in the DQ-2.0 group and 86.7% (13/15) in the CAZ group. As for these two rates, there were no significant differences among the three groups. On exclusion of Enterococcus faecalis which is not indicated, both the overall efficacy rate and the bacteriological eradication rate were both 100% in the CAZ group. A clinical adverse reactions were seen in only one patient in the DQ-2.0 group, who showed mild facial erythema. Abnormal laboratory findings were found in two patients in each of the three groups. As to the incidence of clinical and laboratory adverse reactions, there were no significant differences among the three groups. The results of this open clinical trial and the dose-determination study suggest that DQ-2556 is effective against complicated UTI and that the optimal daily dosage is 0.5g twice a day (0.5g b. i.d.), although a dose of more than l.0g b.i.d. may be needed for intractable UTI such as that associated with indwelling-catheter disease.

Original languageEnglish
Pages (from-to)1195-1217
Number of pages23
JournalCHEMOTHERAPY
Volume41
Issue number11
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology
  • Drug Discovery
  • Oncology

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    Kamidono, S., Arakawa, S., Yamashita, M., Takagi, S., Oshima, H., Kataoka, N., Nakamura, I., Izumi, T., Yamada, Y., Sugimoto, M., Hazama, M., Sengoku, A., Kumamoto, Y., Hirose, T., Yamaguchi, Y., Sato, Y., Aso, Y., Oshi, M., Nito, H., ... Kataoka, N. (1993). Clinical evaluation of DQ-2556, a new parenteral cephem antibiotic, and a dose-determination study in complicated urinary tract infections. CHEMOTHERAPY, 41(11), 1195-1217. https://doi.org/10.11250/chemotherapy1953.41.1195