The importance of the level of metronidazole resistance for the success of Helicobacter pylori eradication

Aliment Pharmacol Ther. 2004 Jun 15;19(12):1315-21. doi: 10.1111/j.1365-2036.2004.01959.x.


Aims: To evaluate the role of antibiotic susceptibility for the treatment outcome of proton pump inhibitor-dependent and independent Helicobacter pylori eradication regimens.

Methods: In a placebo-controlled clinical study of peptic ulcer patients with H. pylori infection, patients were randomized to receive lansoprazole, clarithromycin and tinidazole twice-daily, clarithromycin and tinidazole once-daily with lansoprazole or with placebo. Helicobacter pylori status was assessed by culture and antibiotic susceptibility by E-test minimal inhibitory concentration (MIC) in 205 clinical isolates.

Results: Primary resistance to clarithromycin and metronidazole was 1 and 76%, respectively. In metronidazole susceptible strains eradication rates were similar at > 90% for all treatment groups (P = 0.49). With low-level metronidazole resistance (4 microg/mL < MIC < 256 microg/mL), eradication rates were similar at >75% (P = 0.80). The major difference was found at high-level metronidazole resistance (MIC >or= 256 microg/mL) with 95%, 58% and 21% eradication in the lansoprazole, clarithromycin and tinidazole twice-daily, lansoprazole, clarithromycin and tinidazole once-daily and placebo, clarithromycin and tinidazole once-daily groups, respectively (P < 0.001).

Conclusion: In the absence of antibiotic resistance, a once-daily therapy of only clarithromycin and tinidazole can achieve a high rate of H. pylori eradication. Such a combination could offer a simpler and cheaper treatment option for developing countries. The standard, twice-daily proton pump inhibitor-based triple therapy was shown to be efficient in H. pylori eradication even in the presence of high-level metronidazole resistance.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Ulcer Agents / therapeutic use
  • Clarithromycin / therapeutic use
  • Drug Administration Schedule
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects*
  • Humans
  • Lansoprazole
  • Metronidazole / therapeutic use*
  • Microbial Sensitivity Tests
  • Omeprazole / analogs & derivatives*
  • Omeprazole / therapeutic use
  • Peptic Ulcer / microbiology
  • Proton Pump Inhibitors
  • Tinidazole / therapeutic use
  • Treatment Outcome


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Proton Pump Inhibitors
  • Tinidazole
  • Lansoprazole
  • Metronidazole
  • Clarithromycin
  • Omeprazole