Annual change of primary resistance to clarithromycin among Helicobacter pylori isolates from 1996 through 2008 in Japan

Helicobacter. 2009 Oct;14(5):86-90. doi: 10.1111/j.1523-5378.2009.00714.x.


Background: Recent studies have shown that the combination of proton pump inhibitor, amoxicillin and clarithromycin is one of the best choices for Helicobacter pylori eradication therapy. However, increasing number of cases of H. pylori infection showing resistance to clarithromycin therapy has been reported and this is currently the main cause of eradication failure. We investigated the annual changes of the antimicrobial susceptibility to clarithromycin, amoxicillin and minocycline during a period of 12 years in Japan.

Methods: This study comprised 3521 patients (mean age (SD), 55.4 (13.7) years-old, 2467 males and 1054 females) positive for H. pylori as assessed by microaerobic bacterial culture from 1996 through 2008. All patients were previously untreated for H. pylori and were enrolled in the study to assess primary resistance to the three antibiotics.

Results: The overall primary resistance to clarithromycin, amoxicillin and minocycline were 16.4%, (577/3521), 0.03% (1/3521) and 0.06% (2/3521), respectively. From 1996 through 2004, the resistance rate to clarithromycin increased gradually to approximately 30% and then it remained without marked fluctuation since 2004. Analysis by gender showed a significant increase (p < .0001) in resistance rate to clarithromycin among females (217/1057, 20.6%) compared to males (360/2467, 14.6%). Analysis by age, disclosed significantly (p < .0001) higher resistance rate to clarithromycin in patients of more than 65-years-old compared to the younger population.

Conclusions: The resistance rate of H. pylori infection to clarithromycin in Japan has increased gradually to approximately 30% from 1996 through 2004, and remained unchanged since 2004. Elderly and females were at high risk of having resistance to clarithromycin. Our results suggested that the level of clarithromycin resistance in Japan has now risen to the point where it should no longer be used as empiric therapy.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Clarithromycin / pharmacology*
  • Drug Resistance, Bacterial*
  • Female
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / isolation & purification
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Minocycline / pharmacology


  • Anti-Bacterial Agents
  • Amoxicillin
  • Minocycline
  • Clarithromycin