Helicobacter pylori (H Pylori) infection is associated with functional dyspepsia, peptic ulcer disease, atrophy and gastric cancer. The bacterium has been classified as grade I carcinogen by the WHO in 1994(1). Based on the clinical and microbiological data it is now well known to be the strongest risk factor for developing intestinal type and diffuse type of adenocarcinoma(2-4). While testing and treating asymptomatic persons is a grey area, it is now recommended to rule out H. pylori in un-investigated dyspepsia patients (5-7), and if detected, it must be treated. However, worldwide and especially in the Asian countries, we face a widespread problem of antibiotic resistance(8,9). Regimens are typically selected based on the varying regional clarithromycin resistance(6,9). There is a need for an efficient and reliable empirical therapy that can be universal, has maximal eradication rates irrespective of resistance patterns, has good compliance and minimal adverse events without the emergence of superbugs. We also need a reliable rescue therapy for H. pylori eradication failure.

Inclusion Criteria:

• Adult (18 years - 80 years)
• Patient visiting clinic with dyspepsia, GERD, or non-bleeding peptic ulcer
• 13C-urea breath test (UBT) positive/ Rapid urease test positive (RUT) on endoscopic biopsy
• Off PPIs for 2 weeks

Exclusion Criteria:

• Penicillin allergy
• Recent use of antibiotics in the past 1 month
• Previous H. pylori therapy
• Intestinal metaplasia, gastric cancer, bleeding peptic ulcer
• Patient who is unable to understand study protocol or not consenting
• Pregnancy, lactation
• Patient on anticoagulation, NSAIDs
• Patient using drugs with interactions with vonoprazan, amoxicillin, clarithromycin or PPIs
• Cirrhosis, Chronic kidney disease, chronic lung disease