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

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. 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 [C-13]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined. 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, PaEuroS=aEuroS0.003 (PP) and 89.8% versus 82.4%, PaEuroS=aEuroS0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (PaEuroS=aEuroS0.039), as were CYP2C19 extensive metabolizer (PaEuroS=aEuroS0.005), clarithromycin (PaEuroS=aEuroS0.000) and metronidazole resistance (PaEuroS=aEuroS0.000). 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. 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.