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JAC Advance Access published online on September 7, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm329
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Effect of plaunotol in combination with clarithromycin against clarithromycin-resistant Helicobacter pylori in vitro and in vivo

Makoto Sasaki1,*, Tsutomu Mizoshita1, Takashi Mizushima1, Harumi Inoue2, Takeshi Kamiya1, Hiromi Kataoka1, Naotaka Ogaswara1, Tsuneya Wada1, Eiji Kubota1, Yoshinori Mori1, Takaya Shimura1, Hirokazu Hirata1, Kenji Ando1, Yasuyuki Okamoto1, Hirotaka Ohara1, Haruhisa Nakao1 and Takashi Joh1

1 Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Nagoya 467-8601, Japan 2 Biological Research Laboratories IV, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, Japan

Received 28 June 2007; returned 9 June 2007; revised 3 August 2007; accepted 4 August 2007

* Corresponding author. Tel: +81-52-8538211; Fax: +81-52-8520952; E-mail: msasaki{at}med.nagoya-cu.ac.jp

Objectives: Recently, there has been a decrease in the eradication rate of Helicobacter pylori due to the increase in antibiotic resistance of this bacterium. Plaunotol, a cytoprotective anti-ulcer agent, exhibits antibacterial activity against H. pylori. The purpose of the present study was to investigate the effect of plaunotol in combination with clarithromycin against clarithromycin-resistant H. pylori clinical isolates.

Methods and results: In the chequerboard titration method, the combination of plaunotol and clarithromycin showed a synergistic effect against 67% (10/15) clarithromycin-resistant strains and an additive effect against the other strains. No indifferent and antagonistic effects were observed against any of the strains tested. In a gastritis model of Mongolian gerbils infected with clarithromycin-resistant H. pylori, the plaunotol (40 mg/kg) and clarithromycin (66.6 mg/kg) combination exhibited synergistic effects; however, neither plaunotol nor clarithromycin alone showed bactericidal effects.

Conclusions: These results suggest that plaunotol may play a useful role in combination with anti-H. pylori drugs in the treatment of diseases associated with clarithromycin-resistant H. pylori.

Key Words: synergistic effect , cytoprotective anti-ulcer agent , eradication


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