Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance

Dig Dis Sci. 2014 Jun;59(6):1235-43. doi: 10.1007/s10620-014-3093-7. Epub 2014 Mar 6.

Abstract

Background: Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori (H. pylori) has decreased.

Aims: To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade.

Methods: We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202 H. pylori-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method.

Results: In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (P = 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2-17.2%, P = 0.003) and clarithromycin (23.2-37.3%, P = 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2%, P = 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m(2), amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95% CI, 5.58-29.18; P < 0.001).

Conclusions: An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of H. pylori.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amoxicillin / administration & dosage
  • Amoxicillin / pharmacology
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Clarithromycin / administration & dosage
  • Clarithromycin / pharmacology
  • Clarithromycin / therapeutic use
  • Cytochrome P-450 CYP2C19
  • Drug Resistance, Bacterial*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype*
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / genetics
  • Helicobacter pylori / drug effects*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Odds Ratio
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / therapeutic use
  • Treatment Failure

Substances

  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Amoxicillin
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Clarithromycin