title: Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, South Korea.
authors.forename: Ju Yup
authors.initials: JY
authors.lastname: Lee
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Choi
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Hyuk
authors.initials: H
authors.lastname: Yoon
authors.forename: Cheol Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Hyun Chae
authors.initials: HC
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D024881:Drug Resistance, Bacterial; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016017:Odds Ratio; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D000658:Amoxicillin; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D017291:Clarithromycin