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Antimicrobial Agents and Chemotherapy, September 2001, p. 2455-2459, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2455-2459.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro and In Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of Helicobacter pylori Infection

Tsuneo Kanamaru,1,dagger Yoshitaka Nakano,1 Yukio Toyoda,1 Ken-Ichiro Miyagawa,1 Mayumi Tada,2 Tomoko Kaisho,2 and Masafumi Nakao2,*

Pharmaceutical Discovery Research Laboratories IV, Pharmaceutical Discovery Research Division,1 and Pharmaceutical Research Laboratories II, Pharmaceutical Research Division,2 Takeda Chemical Industries, Ltd., Osaka 532-8686, Japan

Received 15 March 2001/Returned for modification 18 April 2001/Accepted 4 June 2001

The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 µg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of H. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

* Corresponding author. Mailing address: Vaccine Group, Marketing Division, Takeda Chemical Industries, Ltd., 1-1, Doshomachi 4-chome, Chuo-ku, Osaka 540-8645, Japan. Phone: 81-6-6204-2517. Fax: 81-6-6204-2327. E-mail: Nakao_Masafumi{at}takeda.co.jp.

dagger Present address: Hagoromo Gakuen Junior College, Higashi-hagoromo 1-11-57, Takaishi City, Osaka 592-8344, Japan.

Antimicrobial Agents and Chemotherapy, September 2001, p. 2455-2459, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2455-2459.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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