title: Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates.
abstract: BACKGROUND
  Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates.
  
  
  METHODS
  This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing.
  
  
  RESULTS
  Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126-30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014).
  
  
  CONCLUSIONS
  Despite good compliance and safety, hybrid therapy as first-line regimen in populations with high antibiotic resistance rates had unsatisfactory efficacy, primarily due to dual clarithromycin and metronidazole resistance.
authors.affiliation: Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, Peking University Third Hospital, Beijing, China. zhouliya123456@163.com.
authors.forename: Liya
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Bai
authors.affiliation: Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System
keywords: Helicobacter pylori; antibiotic resistance; clarithromycin; first-line; hybrid therapy; metronidazole