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Background/Aims: The purpose of this study was to evaluate the efficacy and tolerability of dual therapy consisting of esomeprazole and amoxicillin as a rescue therapy for Helicobacter pylori infection. Methods: From December 2009 to August 2010, 21 patients who experienced two consecutive eradication failures were included. They received esomeprazole (40 mg, b.i.d.) and amoxicillin (1,000 mg, b.i.d.) for 14 days as a third eradication regimen. Compliance and side effects were determined from an interview. H. pylori status was evaluated using the ^(13)C urea breath test at least 6 weeks after treatment. Results: The mean age of the patients was 59 years and included 52% males. Indications for treatment were functional dyspepsia (61.9%), peptic ulcer disease (28.6%), and gastric adenoma (9.5%). H. pylori was eradicated in 14 of 21 (66.7%) patients. Minor side effects were reported in three of the 21 patients (14.3%). These side effects consisted mainly of nausea and epigastric discomfort. Conclusions: A 2-week course of dual therapy failed to show satisfactory results in third-line H. pylori eradication, but it was very safe and tolerable. Therefore, dual therapy constitutes an encouraging empirical strategy for the elderly and infirm patients with multiple previous eradication failures.

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