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Antimicrobial Agents and Chemotherapy, September 2006, p. 3062-3069, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00036-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

In Vitro Activity of a Novel Antimicrobial Agent, TG44, for Treatment of Helicobacter pylori Infection

Osamu Kamoda,1,3,4* Kinsei Anzai,2 Jun-ichi Mizoguchi,2 Masatoshi Shiojiri,2 Toshiharu Yanagi,2 Takeshi Nishino,3 and Shigeru Kamiya4

Quality Assurance Division, Nagase ChemteX Corporation, 1-58-1, Osadano-cho, Fukuchiyama, Kyoto 620-0853, Japan,1 Bio/Fine Chemicals Division, Nagase ChemteX Corporation, 2-2-3 Murotani, Nishi-ku, Kobe, Hyogo 651-2241, Japan,2 Department of Microbiology, Kyoto Pharmaceutical University, Misasagi-Nakauchicho 5, Yamashina, Kyoto 607-8414, Japan,3 Department of Infectious Disease, Division of Medical Microbiology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan4

Received 10 January 2006/ Returned for modification 13 February 2006/ Accepted 6 June 2006

Due to concerns about the current therapeutic modalities for Helicobacter pylori infection, e.g., the increased emergence of drug-resistant strains and the adverse reactions of drugs currently administered, there is a need to develop an anti-H. pylori agent with higher efficacy and less toxicity. The antibacterial activity of TG44, an anti-H. pylori agent with a novel structural formula, against 54 clinical isolates of H. pylori was examined and compared with those of amoxicillin (AMX), clarithromycin (CLR), and metronidazole (MNZ). Consequently, TG44 inhibited the growth of H. pylori in an MIC range of 0.0625 to 1 µg/ml. The MIC ranges of AMX, CLR, and MNZ were 0.0078 to 8 µg/ml, 0.0156 to 64 µg/ml, and 2 to 128 µg/ml, respectively. The antibacterial activity of TG44 against AMX-, CLR-, and MNZ-resistant strains was nearly comparable to that against drug-susceptible ones. In a pH range of 3 to 7, TG44 at 3.13 to 12.5 µg/ml exhibited potent bactericidal activity against H. pylori in the stationary phase of growth as early as 1 h after treatment began, in contrast to AMX, which showed no bactericidal activity at concentrations of up to 50 µg/ml at the same time point of treatment. TG44 at 25 µg/ml exhibited no antibacterial activity against 13 strains of aerobic bacteria, suggesting that its antibacterial activity against H. pylori is potent and highly specific. The present study indicated that TG44 possesses antibacterial activity which manifests quickly and is potentially useful for eradicating not only the antibiotic-susceptible but also the antibiotic-resistant strains of H. pylori by monotherapy.

* Corresponding author. Mailing address: Quality Assurance Division, Nagase ChemteX Corporation, 1-58-1, Osadano-cho, Fukuchiyama, Kyoto 620-0853, Japan. Phone: 81-773-27-8745. Fax: 81-773-27-8746. E-mail: osamu.kamoda{at}ncx.nagase.co.jp.

Antimicrobial Agents and Chemotherapy, September 2006, p. 3062-3069, Vol. 50, No. 9
0066-4804/06/$08.00+0     doi:10.1128/AAC.00036-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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