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

Int J Antimicrob Agents. 2012 Apr;39(4):352-5. doi: 10.1016/j.ijantimicag.2011.12.002. Epub 2012 Feb 7.

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 MIC(90) (MIC for 90% of the organisms) of STX was 5 log(2) dilutions lower than that of levofloxacin (LVX). The MIC(50) (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 100mg 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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • DNA Gyrase / genetics
  • Disease Eradication / methods
  • Drug Resistance, Bacterial*
  • Female
  • Fluoroquinolones / pharmacology*
  • Fluoroquinolones / therapeutic use
  • Genes, Bacterial
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / isolation & purification
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Japan / epidemiology
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation
  • Pepsinogen A / chemistry
  • Pepsinogen C / chemistry
  • Prospective Studies

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Pepsinogen C
  • Amoxicillin
  • Pepsinogen A
  • sitafloxacin
  • DNA Gyrase