The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A Nationwide Study

PLoS One. 2015 May 5;10(5):e0124199. doi: 10.1371/journal.pone.0124199. eCollection 2015.


Objective: The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.

Methods: The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.

Results: The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000-2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.

Conclusions: The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / pharmacology
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Clarithromycin / pharmacology
  • Clarithromycin / therapeutic use
  • Female
  • Genotype
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / growth & development*
  • Humans
  • Male
  • Metronidazole / pharmacology
  • Metronidazole / therapeutic use
  • Taiwan
  • Tetracycline / pharmacology
  • Tetracycline / therapeutic use
  • Virulence Factors


  • Anti-Bacterial Agents
  • Virulence Factors
  • Metronidazole
  • Amoxicillin
  • Tetracycline
  • Clarithromycin

Grant support

JML was funded by the National Clinical Trial Center of National Taiwan University Hospital (NTUH103 -002516) and MSW was funded by the National Science Council, Executive Yuan, ROC, Taiwan (NSC 100-2325-B-002-063, 101-2325-B-002-074, and 102-2325-B-002-074). All authors do not have conflicts of interests that are relevant to the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.