Y-754, a novel
benzimidazole compound, was investigated for in vitro and in vivo antibacterial activity. Unlike
amoxicillin,
clarithromycin, and
metronidazole, the compound had no activity against common aerobic and anaerobic bacteria other than Helicobacter pylori. The minimum inhibitory concentration of
Y-754 against H. pylori, at 0.025 microg/ml, was nearly equal to that of
amoxicillin and
clarithromycin. The respective concentrations of
Y-754,
amoxicillin,
clarithromycin, and
metronidazole required to inhibit 90% of 39 isolates of H. pylori were 0.05, 0.39, 6.25, and 25 microg/ml, indicating the potent activity of
Y-754, including activity against
clarithromycin- and
metronidazole-resistant strains. The anti-H. pylori activity of
Y-754 was potent even at pH 5.5 and was bactericidal at concentrations of 0.1 microg/ml and above. Exposure of H. pylori to
Y-754 did not result in the induction of
drug-resistant mutation.
Oral administration (10 mg/kg twice a day for 7 days) to Mongolian gerbils infected with strain ATCC 43504 demonstrated that
Y-754 was effective in H. pylori eradication and that its eradication efficacy increased in line with the progress of damage to the gastric mucosa caused by H. pylori
infection.
Y-754 was also efficacious in the treatment of
infection by the
clarithromycin-resistant strain OIT-36. The results obtained lead to the expectation that the new
benzimidazole Y-754 will, in the near future, be used for H. pylori eradication
therapy in
peptic ulcer patients.