In vitro and in vivo anti- Helicobacter pylori activity of Y-904, a new fluoroquinolone

 Y-904 is a new fluoroquinolone with a broad antimicrobial spectrum. In particular, it has anti-Helicobacter pylori activity superior to that of existing fluoroquinolones. In the present study it was examined for its in vitro antibacterial activity against 51 clinical isolates of H. pylori, including clarithromycin- and metronidazole-resistant strains. The minimum inhibitory concentration of Y-904 at which 90% of isolates were inhibited was close to that of amoxicillin and clarithromycin and lower than that of levofloxacin and metronidazole (0.1, 0.1, 0.2, 3.13, and 12.5 μg/ml, respectively). Y-904 showed equally strong activity at pH 5.5 as at pH 7.0. At 10 times the minimum inhibitory concentration, Y-904 decreased the viable count of H. pylori to below 10⁻⁵ within 2 h after exposure. No significant change in the minimum inhibitory concentration was observed when H. pylori, Staphylococcus aureus, and Escherichia coli were successively subcultured in medium containing subinhibitory concentrations of Y-904. Y-904 also strongly inhibited the supercoiling activity of DNA gyrase from H. pylori ATCC43504 (IC₅₀, 1.48 μg/ml). A study of Y-904 treatment in H. pylori-infected Mongolian gerbils using twice-daily oral administration for 7 days demonstrated that the complete clearance dose of Y-904 was 1 mg/kg and that its potency was around 10, 30, and 30 times that of amoxicillin, clarithromycin, and levofloxacin, respectively. These results indicate that Y-904 is a promising candidate for the eradication of H. pylori infection. Received: November 8, 2002 / Accepted: March 10, 2003 Acknowledgments We thank Dr. T. Sugiyama, Dr. M. Kato (Hokkaido University, Sapporo, Japan), and Dr. K. Sakurai (Showa University, Yokohama, Japan) for graciously providing the clinical isolates of H. pylori. We are also grateful to Mr. K. Honjo for assistance in the in vitro antibacterial studies and to Mr. S. Miyoshi for pharmacokinetic data.