Helicobacter pylori eradication therapy outcome according to clarithromycin susceptibility testing in Japan

Helicobacter. 2020 Aug;25(4):e12698. doi: 10.1111/hel.12698. Epub 2020 May 5.

Abstract

Background: Helicobacter pylori (Hp) infection increases the risk of gastric cancer. Therefore, eradication is a global goal, which requires continuous monitoring of therapeutic regimens and effectiveness. Clarithromycin resistance is an important contributor to eradication failure, and metronidazole is recommended as second-line treatment in such cases. Here, we retrospectively evaluated the clarithromycin and metronidazole resistance rates and treatment effectiveness in patients with Hp using tailored therapies according to clarithromycin susceptibility testing.

Methods: Data on drug susceptibility were obtained for 5249 Japanese Hp patients between July 2005 and August 2018. Clarithromycin/metronidazole resistance rates were analyzed according to year, gender, and age with Fisher's exact test. The relationship between clarithromycin resistance and Hp therapy outcomes was assessed for 1300 patients. Treatment regimens included a clarithromycin- or metronidazole-containing 7-day triple therapy with one of several proton pump inhibitors and vonoprazan.

Results: Clarithromycin resistance increased annually and was higher in women and younger patients (<30 years). Rates of metronidazole resistance were stable but decreased with age. Hp treatment regimens using PPIs had eradication rates of 88% and 45% among clarithromycin-sensitive and clarithromycin-resistant cases, respectively, while regimens including vonoprazan had eradication rates of around 90% regardless of clarithromycin susceptibility. In particular, triple therapy with vonoprazan, amoxicillin, and metronidazole achieved 98% eradication.

Conclusion: Clarithromycin-containing triple therapy even using vonoprazan did not achieve satisfactory eradication rates even in the clarithromycin-sensitive group. To avoid antibiotic misuse in population with low metronidazole resistance, 7-day vonoprazan, amoxicillin, and metronidazole triple therapy might be a strong candidate as a first-line eradication therapy.

Keywords: clarithromycin resistance; eradication; helicobacter; metronidazole.

MeSH terms

  • Adult
  • Aged
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Clarithromycin / pharmacology*
  • Clarithromycin / therapeutic use
  • Drug Resistance, Bacterial / drug effects*
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / drug effects*
  • Humans
  • Japan / epidemiology
  • Male
  • Metronidazole / pharmacology
  • Metronidazole / therapeutic use
  • Middle Aged
  • Pyrroles / therapeutic use
  • Retrospective Studies
  • Sulfonamides / therapeutic use
  • Treatment Outcome

Substances

  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Anti-Bacterial Agents
  • Pyrroles
  • Sulfonamides
  • Metronidazole
  • Amoxicillin
  • Clarithromycin