Personalized vs Standard of Care Treatment for Helicobacter Pylori Eradication Among Veterans

Inclusion Criteria: * Adult Veterans ages 18 years or older, irrespective of sex/gender (male, female, non-binary, other preferred classification). * Treatment-naïve patients with active H. pylori infection as determined by a positive H. pylori stool antigen (HPsAg), gastric biopsy, or urease breath test. All individuals who test positive based on a non-HPsAg modality will need to have a positive HPsAg documented within 4 weeks of enrollment to be considered eligible. * Subjects who can understand and sign written informed consent. Exclusion Criteria: The investigators will exclude individuals with: * Severe gastrointestinal (GI) symptoms that limit the ability to tolerate study medications. Note: The presence of symptoms or GI diagnoses such as irritable bowel syndrome or gastroesophageal reflux does not impact H. pylori eradication and will not be exclusion criteria unless deemed that symptom severity will impact adherence. * Conditions where urgent H. pylori treatment is recommended (i.e., active peptic ulcer disease (PUD) complicated by bleeding, perforation, or obstruction; gastric neoplasia including MALT lymphoma). Active PUD is defined as having a gastric or duodenal ulcer confirmed on an upper endoscopic procedure in the 4 weeks prior to eligibility determination. * Inability to be safely off of PPI for two weeks to allow for accurate post-treatment HPsAg testing. These conditions include Barrett's esophagus with dysplasia, active PUD, severe esophagitis defined as Los Angeles Classification C or D esophagitis. * Allergy or severe intolerance/contraindication to any of the treatment components. Note: In patients with penicillin allergy, metronidazole is often substituted for amoxicillin in PPI clarithromycin triple therapy. However, this alternative regimen demonstrates higher failure rates vs. PPI-clarithromycin triple therapy with amoxicillin among Veterans and thus the investigators elected to exclude patients with penicillin allergy. * Severe medical comorbidity that is a threat to life. This includes, but is not limited to, coronary artery disease with myocardial infarction or equivalent (e.g., cerebrovascular event) within 12 months, unstable angina or congestive heart failure, cardiac or vascular stent placement within 12 months, chronic obstructive pulmonary disease requiring home oxygen, decompensated cirrhosis, end-stage renal disease, other diseases that limit life expectancy to less than 5 years. * Any prior history of upper gastrointestinal surgery or gastric cancer diagnosis. * Past liver transplant or allogenic bone marrow transplant, given that pharmacogenomic testing is inaccurate for these patients. * Any history of recurrent Clostridioides difficile infection (CDI), defined as an episode of CDI occurring within 8 weeks of a previous CDI episode; or any episode of CDI within the preceding 12 months. * Evidence of any overt gastrointestinal bleeding. * History of photosensitive reactions to any medications. * Women who are pregnant, lactating, or of childbearing age without reliable contraception (Note: all women of childbearing age will be asked to submit a urine pregnancy test prior to enrollment). * Prior CYP2C19 or PHASER testing or HP antimicrobial susceptibility profiling before enrollment.