Eradication of Helicobacter pylori with 10-day and 14-day Rifabutin-based Triple Therapy as a Third- or Fourth-line Rescue Therapy: An Open-label Randomized Pilot Trial

Abstract

Introduction: Recently, we reported that few Helicobacter pylori strains are resistant to rifabutin in Japan (Antimicrob Agents Chemother. 55:5374-5, 2011). This prospective study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy. Methods: From October 2013 to May 2015, a total of 28 patients in whom eradication treatment with clarithromycin-based first-line therapy and metronidazole-based second-line therapy failed were enrolled. Furthermore, 19 of the 28 patients had failed to third-line sitafloxacin-based triple therapy. Before beginning the treatment, H. pylori were isolated from gastric biopsy specimens, and the minimum inhibitory concentrations (MICs) of sitafloxacin and metronidazole were determined using agar dilution method. The susceptibility-resistance cutoff values of the MICs for rifabutin were defined as 0.25 μg/mL. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole, amoxicillin, and rifabutin. Poor compliance was defined as intake of 13C urea breath test or a stool antigen test, 12 weeks after the end of therapy. Results: In ITT analysis, the eradication rate of 10-day therapy was 81.8% (9/11), and that of 14-day therapy was 94.1% (16/17). Only 1 patient were infected with the rifabutin resistant strain (MIC=1.0μg/mL) that were eradicated with 14-day therapy finally. The medication adherence rates of 14-day therapy were 64.7% (11/17), whereas that of 10-day therapy were 100%(11/11) (P=0.05). Major adverse events were diarrhea/soft stool, fever, headache, liver, rush, stomatitis and leucopoenia. As the most serious adverse events, 1 patient developed neutropenia (250/mm3) with 10-day treatment, but after the eradication treatment she spontaneously recovered. Other all adverse events were also recovered after the cessation of eradication therapy. Conclusion: Both of the 10-day and 14-day therapies were most effective as rescue regimens, especially 14-day therapy achieved over 90 % eradication. On the other hand, 10-day treatment were more tolerable than 14-day therapy.