770 High Cumulative Eradication Rate in the First-Line and Rescue Therapies for Helicobacter pylori Infection by Repeated Optimized High Dose Dual Therapy

Abstract

Background: The increased primary and acquired resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin have resulted in a significant reduction in the efficacy of various anti-H. pylori regimens. We recently demonstrated that an optimized high-dose dual therapy (HDDT) is superior to the standard triple therapy (TT) or sequential therapy (ST) for H. pylori infection in a large-scale multi-hospital, randomized, comparative study (Clinical Gastro & Hepato, in press). Because the global prevalence of primary and acquired resistance to amoxicillin (AMO) is rare, we hypothesize that HDDT can be used repeatedly and empirically for H. pylori treatment without a reduction of eradication efficacy. Aim: To evaluated the cumulative efficacy of repeated HDDT treatment for first-line and rescue antiH. pylori therapy. Methods: A total of 618 patients with H. pylori infection diagnosed by endoscopy with biopsy for histology examination and bacterial culture were recruited in this multi-hospital study and were randomly allocated to receive HDDT, TT, or ST for therapy. As reported in our previous study, H. pylori was eradicated in 143 out of 150 (95.3%; 95% C.I. 92.9-97.8) treatment-naive patients receiving the first course of HDDT (rabeprazole 20 mg + AMO 750 mg, qid for 14 days). Six patients who failed in the first HDDT treatment received the second course of HDDT. For treatment-experienced patients, 68 out of 84 patients failed in TT and 25 out of 45 patients failed in ST received the first course of HDDT. The second course of HDDT was used again if the first course failed. Four to eight weeks after termination of each treatment, H. pylori infection status was examined by the C13-urea breath test. The E-test was used to evaluate the antibiotics resistances of H. pylori strains before and after failed treatment of repeated HDDT. Results: Five out of 6 treatment-naive patients had successfully H. pylori eradication by a second course of HDDT, resulting in a cumulative eradication rate of 98.7% (148/150; 95% C.I. 97.3-100.0) in the intention-to-treat (ITT) analysis, and 99.3% (148/149; 95% C.I. 98.4-100.3) in perprotocol (PP) analysis. For the treatment-experienced patients, H. pylori was successfully eradicated in 90.3% (84/93; 95% C.I. 85.9-94.7) of patients with first course of HDDT treatment. Seven out of 9 patients who failed in the first HDDT treatment achieved H. pylori eradication with a second course of HDDT. The cumulative eradication rate was 97.8% (91/ 93; 95% C.I. 95.7-100.0) in both ITT and PP analyses. The susceptibility of H. pylori to antibiotics did not significantly impact eradication rates. Conclusion: HDDT consisting of a PPI and AMO given four times daily is highly efficacious when it is used repeatedly for H. pylori eradication. Thus, H. pylori susceptibility testing may be avoided by using HDDT.