Empirical modified sequential therapy containing levofloxacin and high-dose esomeprazole in second-line therapy for Helicobacter pylori infection: a multicentre clinical trial

J Antimicrob Chemother. 2011 Aug;66(8):1847-52. doi: 10.1093/jac/dkr217. Epub 2011 May 31.

Abstract

Objectives: Sequential therapy appears to achieve a higher Helicobacter pylori eradication rate than triple therapy. We assessed the efficacy and tolerability of modified sequential therapy containing levofloxacin and high-dose esomeprazole in second-line therapy.

Methods: Patients who failed first-line triple therapy with clarithromycin, amoxicillin and a proton pump inhibitor were eligible in this multicentre trial. Eligible patients were treated with esomeprazole 40 mg and amoxicillin 1 g for the first 5 days, followed by esomeprazole 40 mg, levofloxacin 250 mg and metronidazole 500 mg for another 5 days (all given twice daily). Eradication was confirmed with a (13)C-urea breath test 6 weeks after therapy. Drug susceptibility, presence/absence of gyrA mutation and CYP2C19 genotype were also determined.

Results: A total of 142 patients were enrolled. The eradication rate was 95.1% [135/142, 95% confidence interval (CI) 91.5%-98.6%] in the intention-to-treat analysis and 96.4% (133/138, 95% CI 93.3%-99.5%) in the per protocol analysis. Four patients (2.8%) failed to take at least 80% of the drugs due to adverse effects. The eradication rates were 50% (4/8) and 97.7% (43/44) in patients with and without metronidazole resistance, respectively (P = 0.001). The eradication rates were 84.6% (11/13) and 95.1% (58/61) in patients with and without gyrA mutation, respectively (P = 0.210). The eradication rates were not affected by the CYP2C19 polymorphism (P = 0.421).

Conclusions: This modified sequential therapy achieved an excellent eradication rate (>95%) in second-line treatment and the eradication rate appeared to be affected by metronidazole resistance.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Breath Tests / methods
  • Cytochrome P-450 CYP2C19
  • DNA Gyrase / genetics
  • Drug Monitoring / methods
  • Esomeprazole / administration & dosage*
  • Esomeprazole / adverse effects
  • Female
  • Genotype
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects*
  • Humans
  • Levofloxacin*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Ofloxacin / administration & dosage*
  • Ofloxacin / adverse effects
  • Prospective Studies
  • Treatment Outcome
  • Urea / analysis

Substances

  • Anti-Bacterial Agents
  • Levofloxacin
  • Urea
  • Ofloxacin
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • DNA Gyrase
  • Esomeprazole