| Summary: | Bismuth quadruple therapy (BQT) is an effective treatment for <i>Helicobacter pylori</i> infection. However, frequent dosing schedules of BQT regimen often compromise drug adherence and may affect treatment outcomes. This retrospective study aimed to investigate the efficacy of twice-daily BQT compared to that of four times a day therapy. From August 2018 to November 2020, adult patients who failed first-line standard triple therapy and underwent BQT were eligible. Patients were categorized into two groups according to dosing schedule: (i) the BQT group (<i>n</i> = 213) who received standard BQT administered four times a day; and (ii) the BQTb group (<i>n</i> = 141) who received proton pump inhibitor, bismuth 600 mg, metronidazole 500 mg, and tetracycline 1 g twice a day. The eradication rate did not differ between the BQT (92.5%) and the BQTb groups (90.1%) (<i>p</i> = 0.441). Adherence and adverse event rate were similar between the two groups. Multivariate analysis showed that current smoking was associated with eradication failure; however, dosing frequency was not associated with the efficacy of eradication therapy. This study suggested that twice a day BQT is as effective as four times a day therapy for second-line treatment of <i>H. pylori</i> infection.
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