Modified sequential Helicobacter pylori therapy: proton pump inhibitor and amoxicillin for 14 days with clarithromycin and metronidazole added as a quadruple (hybrid) therapy for the final 7 days

Helicobacter. 2011 Apr;16(2):139-45. doi: 10.1111/j.1523-5378.2011.00828.x.


Background: Ten-day sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole typically achieves Helicobacter pylori eradication rates of 90-94% (Grade B success).

Aims: We tested whether prolonging treatment and continuing amoxicillin throughout the 14-day treatment period would produce a ≥ 95% result.

Methods: This was a multicenter pilot study in which H. pylori-infected patients received a 14-day sequential-concomitant hybrid therapy (esomeprazole and amoxicillin for 7 days followed by esomeprazole, amoxicillin clarithromycin, and metronidazole for 7 days). H. pylori status was examined 8 weeks after therapy. Success was defined as achieving ≥ 95% eradication by per-protocol analysis.

Results: One hundred and seventeen subjects received hybrid therapy. The eradication rate was 99.1% (95% confidence interval (CI), 97.3-100.0%) by per-protocol analysis and 97.4% by intention-to-treat analysis (95% CI, 94.5-100.0%). Adverse events were seen in 14.5%; drug compliance was 94.9%.

Conclusions: Fourteen-day hybrid sequential-concomitant therapy achieved > 95%H. pylori eradication (Grade A result). Further studies are needed 1, in regions with different patterns and frequencies of resistance to confirm these findings, and 2, to examine whether Grade A success is maintained with hybrid therapy shorter than 14 days.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amoxicillin / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Clarithromycin / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections / drug therapy*
  • Humans
  • Male
  • Metronidazole / therapeutic use*
  • Middle Aged
  • Proton Pump Inhibitors / therapeutic use*
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Metronidazole
  • Amoxicillin
  • Clarithromycin