Primary and acquired Helicobacter pylori resistance to clarithromycin, metronidazole, and amoxicillin--influence on treatment outcome

Am J Gastroenterol. 1998 Mar;93(3):386-9. doi: 10.1111/j.1572-0241.1998.00386.x.


Objective: The aim of this study was to evaluate the primary and acquired resistance of H. pylori against clarithromycin, metronidazole, and amoxicillin, and to elucidate the consequential influence on H. pylori eradication.

Methods: A total of 195 patients with positive H. pylori status were consecutively included. In 172 patients, H. pylori could be cultured for evaluation of primary antibiotic resistance. Fifty patients received a 2-wk dual therapy with an acid inhibitor and amoxicillin 2,000 mg daily (A), the other 122 patients a 1-wk modified triple therapy with the acid inhibitor clarithromycin 500-1,000 mg daily, and metronidazole 1,000-1,500 mg daily (B: n = 78), or amoxicillin 2,000 mg daily and metronidazole 1,000 mg daily (C: n = 44), respectively. Acid inhibition was conducted with pantoprazole 40 mg b.i.d. (n = 62), omeprazole 20 mg b.i.d. (n = 50), lansoprazole 30 mg b.i.d. (n = 10), or ranitidine 150 mg t.i.d. (n = 50). After therapy, 36 patients remained H. pylori-positive, 20 after dual therapy (A) and 16 after modified triple therapy (B: n = 7, C: n = 9). In 32 of these patients, H. pylori could be recultured for evaluation of acquired resistance (A: n = 18, B: n = 7, C: n = 7).

Results: Primary H. pylori resistance to metronidazole was observed in 36 of 172 patients (21%) and to clarithromycin in three of 172 (2%). Acquired resistance was found in six of 14 (43%) and in two of seven (29%), respectively, whereas neither primary nor acquired H. pylori resistance to amoxicillin was noted. Patients infected with metronidazole resistant H. pylori strains were successfully treated in combination with clarithromycin (eight of nine vs 63 of 67 with sensitive strains, NS), but not with amoxicillin (one of eight vs 32 of 34 with sensitive strains, p < 0.0001). In two patients with acquired combined clarithromycin and metronidazole resistance, modified triple therapy failed.

Conclusion: The value of modified triple therapy with amoxicillin and metronidazole is significantly limited by metronidazole resistance. However, metronidazole resistance does not negatively influence treatment outcome in modified triple therapy including clarithromycin. H. pylori resistance to amoxicillin still is not present.

MeSH terms

  • Amoxicillin / administration & dosage
  • Amoxicillin / pharmacology*
  • Clarithromycin / administration & dosage
  • Clarithromycin / pharmacology*
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / physiology*
  • Humans
  • Male
  • Metronidazole / administration & dosage
  • Metronidazole / pharmacology*
  • Middle Aged
  • Treatment Outcome


  • Metronidazole
  • Amoxicillin
  • Clarithromycin