Impact of primary antibiotic resistance on the effectiveness of sequential therapy for Helicobacter pylori infection: lessons from a 5-year study on a large number of strains

Aliment Pharmacol Ther. 2018 May;47(9):1261-1269. doi: 10.1111/apt.14597. Epub 2018 Mar 14.


Background: The increasing prevalence of strains resistant to antimicrobial agents is a critical issue in the management of Helicobacter pylori (H. pylori) infection.

Aims: (1) To evaluate the prevalence of primary resistance to clarithromycin, metronidazole and levofloxacin (2) to assess the effectiveness of sequential therapy on resistant strains (3) to identify the minimum number of subjects to enrol for evaluating the effectiveness of an eradication regimen in patients harbouring resistant strains.

Methods: Consecutive 1682 treatment naïve H. pylori-positive patients referred for upper GI endoscopy between 2010 and 2015 were studied and resistances assessed by E-test. Sequential therapy was offered, effectiveness evaluated and analysed.

Results: H. pylori-primary resistance to antimicrobials tested was high, and increased between 2010 and 2015. Eradication rates were (estimates and 95% CIs): 97.3% (95.6-98.4) in strains susceptible to clarithromycin and metronidazole; 96.1% (91.7-98.2) in strains resistant to metronidazole but susceptible to clarithromycin; 93.4% (88.2-96.4) in strains resistant to clarithromycin but susceptible to metronidazole; 83.1% (77.7-87.3) in strains resistant to clarithromycin and metronidazole. For any treatment with a 75%-85% eradication rate, some 98-144 patients with resistant strains need to be studied to get reliable information on effectiveness in these patients.

Conclusions: H. pylori-primary resistance is increasing and represents the most critical factor affecting effectiveness. Sequential therapy eradicated 83% of strains resistant to clarithromycin and metronidazole. Reliable estimates of the effectiveness of a given regimen in patients harbouring resistant strains can be obtained only by assessing a large number of strains.

MeSH terms

  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / administration & dosage*
  • Clarithromycin / therapeutic use
  • Drug Administration Schedule
  • Drug Resistance, Microbial / drug effects*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / epidemiology
  • Helicobacter pylori* / classification
  • Helicobacter pylori* / drug effects
  • Humans
  • Levofloxacin / therapeutic use
  • Male
  • Metronidazole / therapeutic use
  • Microbial Sensitivity Tests
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Metronidazole
  • Levofloxacin
  • Amoxicillin
  • Clarithromycin