Antibiotic resistance and CYP2C19 polymorphisms affect the efficacy of concomitant therapies for Helicobacter pylori infection: an open-label, randomized, single-centre clinical trial

J Antimicrob Chemother. 2016 Aug;71(8):2280-5. doi: 10.1093/jac/dkw118. Epub 2016 Apr 21.

Abstract

Objectives: We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated.

Methods: In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined.

Results: A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, P = 0.003 (PP) and 89.8% versus 82.4%, P = 0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (P = 0.039), as were CYP2C19 extensive metabolizer (P = 0.005), clarithromycin (P = 0.000) and metronidazole resistance (P = 0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious.

Conclusions: The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Bacterial Agents / therapeutic use*
  • Breath Tests
  • China
  • Cytochrome P-450 CYP2C19 / genetics*
  • Drug Resistance, Bacterial*
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori / drug effects*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Polymorphism, Genetic*
  • Prospective Studies
  • Proton Pump Inhibitors / therapeutic use
  • Treatment Outcome
  • Urea / analysis

Substances

  • Anti-Bacterial Agents
  • Proton Pump Inhibitors
  • Urea
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19