High rate of post-therapeutic resistance after failure of macrolide-nitroimidazole triple therapy to cure Helicobacter pylori infection: impact of two second-line therapies in a randomized study

Aliment Pharmacol Ther. 2002 Feb;16(2):315-24. doi: 10.1046/j.1365-2036.2002.01173.x.


Background: The optimal second-line treatment after failed Helicobacter pylori therapy has not been established.

Aims: To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re-treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance.

Methods: Patients after failed triple therapy were randomly allocated to one of two 1-week second-line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post-therapeutic Helicobacter pylori status was assessed by 13C-urea breath test at least 4 weeks after treatment.

Results: The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole-clarithromycin-amoxicillin: intention-to-treat, 43%; per protocol, 50%; omeprazole-bismuth subsalicylate-metronidazole-tetracycline: intention-to-treat, 68%; per protocol, 69%. The frequencies of resistance after first-line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole-clarithromycin-amoxicillin was 30% vs. 83% for clarithromycin susceptibility.

Conclusions: Omeprazole-bismuth subsalicylate-metron- idazole-tetracycline was superior to omeprazole-clarithromycin-amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post-therapeutic dual resistance has a negative impact on omepraz- ole-clarithromycin-amoxicillin, and probably also on omeprazole-bismuth subsalicylate-metronidazole-tetracycline, and limits the choice for second-line treatment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amoxicillin / administration & dosage
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / therapeutic use*
  • Breath Tests
  • Clarithromycin / administration & dosage
  • Clarithromycin / therapeutic use
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / pathology
  • Helicobacter pylori / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Nitroimidazoles / administration & dosage
  • Nitroimidazoles / therapeutic use*
  • Omeprazole / administration & dosage
  • Omeprazole / therapeutic use
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Nitroimidazoles
  • Amoxicillin
  • Clarithromycin
  • Omeprazole