Esomeprazole-Based Helicobacter Pylori Eradication Therapy and The Effect of Antibiotic Resistance: Results of Three Us Multicenter, Double-Blind Trials

OBJECTIVES: To determine the efficacy of once-daily esomeprazole plus antibiotics for eradication of Helicobacter pylori, to assess the effect of antibiotic resistance on eradication rate, and to define the rate of emergent resistance. METHODS: Three separate randomized trials were performed in H. pylori-positive patients with a duodenal ulcer or history of documented duodenal ulcer within 5 yrs: 1) esomeprazole (40 mg once daily), amoxicillin (1 g b.i.d.), and clarithromycin (500 mg b.i.d.; this combination will be referred to as EAC) versus esomeprazole (40 mg once daily) plus clarithromycin (500 mg twice daily; this combination will be referred to as EC); 2) EAC versus esomeprazole (40 mg once daily; E); and 3) EC versus E. Therapy was given for 10 days. Endoscopy and biopsies for CLOtest, histology, and culture with susceptibility testing were done at baseline and 4 wk after completion of therapy. RESULTS: Per-protocol and intent-to-treat eradication rates, respectively, were as follows. For EAC versus EC in study 1 (N = 448), 84 versus 55% and 77 versus 52% (p < 0.001); for EAC versus E in study 2 (N = 98), 85 versus 5% and 78 versus 4% (p < 0.001); for EC versus E in study 3 (N = 66), 50% versus 0 and 46% versus 0 (p < 0.05). The 15% of patients in the combined studies with baseline clarithromycin resistance had significantly lower rates of eradication than those with susceptible strains (EAC: 45 vs. 89%; EC: 13 vs. 61%). Emergent resistance was less common after treatment with EAC 2/6 (33%) than with EC (23/27 85%). CONCLUSIONS: Ten-day triple therapy with once-daily esomeprazole plus twice-daily amoxicillin and clarithromycin achieves an eradication rate virtually identical to that of the twice-daily proton pump inhibitor-based triple therapies. Baseline clarithromycin resistance, present in 15% of patients, predicts a markedly decreased rate. Use of an amoxicillin-containing regimen may decrease emergence of clarithromycin resistance.