Sitafloxacin resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a third-line regimen in Japan

• Published in: International journal of antimicrobial agents 2012-04, Vol.39 (4), p.352-355
• Main Authors: Hirata, Yoshihiro, Ohmae, Tomoya, Yanai, Ayako, Sakitani, Kosuke, Hayakawa, Yoku, Yoshida, Shuntaro, Sugimoto, Takafumi, Mitsuno, Yuzo, Akanuma, Masao, Yamaji, Yutaka, Ogura, Keiji, Maeda, Shin, Koike, Kazuhiko
• Format: Article
• Language: English
• Subjects: amoxicillin; Amoxicillin - pharmacology; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Biological and medical sciences; clinical trials; Disease Eradication - methods; DNA Gyrase - genetics; Drug regimen; Drug resistance; Drug Resistance, Bacterial; Female; Fluoroquinolones - pharmacology; Fluoroquinolones - therapeutic use; Genes, Bacterial; Helicobacter Infections - drug therapy; Helicobacter Infections - epidemiology; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - drug effects; Helicobacter pylori - genetics; Helicobacter pylori - isolation & purification; Human bacterial diseases; Humans; Hydrogen-Ion Concentration; Infectious Disease; Infectious diseases; Inhibitory Concentration 50; Japan - epidemiology; Male; Medical sciences; Microbial Sensitivity Tests; Middle Aged; minimum inhibitory concentration; mutants; Mutation; patients; pepsinogen; Pepsinogen A - chemistry; Pepsinogen C - chemistry; Pharmacology. Drug treatments; Prospective Studies; sitafloxacin; therapeutics
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2011.12.002

Abstract The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of ≤1 μg/mL against all 100 H. pylori isolates, and the MIC90 (MIC for 90% of the organisms) of STX was 5 log2 dilutions lower than that of levofloxacin (LVX). The MIC50 (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 μg/mL and was significantly lower than that of LVX (8 μg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy [rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100 mg b.i.d. for 7 days]. The eradication rate was 75% using intention-to-treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy.