Helicobacter pylori infection, treatment and colorectal cancer risk by genetic predisposition: evidence from two randomised trials.

Confirm ACTIVE infection before treating using a urea breath test, fecal (stool) antigen test, or endoscopic biopsy-based test (histology or rapid urease); do NOT use serology. Testing and treatment are a SINGLE decision, do NOT test unless you intend to treat, and, conversely, offer eradication to EVERY patient found to have confirmed active infection regardless of why they were tested ('if you test, you treat'); confirmed active infection is itself the indication to treat, not one of the conditions below. The following are indications to TEST for H. pylori (and to treat whenever the test is positive): active or prior peptic ulcer disease, gastric MALT lymphoma, atrophic gastritis / gastric intestinal metaplasia and other gastric premalignant conditions, uninvestigated dyspepsia in patients under 60 without alarm features (test-and-treat), functional dyspepsia, long-term NSAID or aspirin use, unexplained iron-deficiency anemia, immune (idiopathic) thrombocytopenic purpura, resected early gastric cancer or gastric adenomas, first-degree relatives of gastric-cancer patients, and adult household members of an infected person (test non-serologically). First-line in treatment-naive patients: the PREFERRED regimen (strong recommendation, moderate quality of evidence) is optimized bismuth quadruple therapy (BQT) for 14 days = standard-dose PPI twice daily + bismuth subcitrate or subsalicylate four times daily + tetracycline 500 mg four times daily + metronidazole 500 mg three or four times daily; 'optimized' means the full 14 days, using tetracycline (do NOT substitute doxycycline) and adequate metronidazole (at least 1.5 g/day). Optimized BQT is preferred even with penicillin allergy; avoid tetracycline in women of childbearing potential and avoid bismuth subsalicylate in salicylate allergy. CONDITIONAL alternatives (low/moderate QOE, require no penicillin allergy) are rifabutin triple therapy (omeprazole 10 mg / amoxicillin 250 mg / rifabutin 12.5 mg, i.e. Talicia, 4 capsules three times daily for 14 days) and vonoprazan-amoxicillin DUAL therapy (vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily for 14 days). Vonoprazan-clarithromycin TRIPLE therapy (vonoprazan 20 mg twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days) should be used ONLY when the strain is clarithromycin-susceptible. AVOID any empiric clarithromycin-containing (including PPI-clarithromycin triple) or levofloxacin-containing regimen unless susceptibility is documented (clarithromycin resistance ~22-31%, levofloxacin ~38%); prefer esomeprazole or rabeprazole, or a PCAB, over omeprazole/lansoprazole/pantoprazole in known rapid or ultrarapid CYP2C19 metabolizers. Test of cure is required for ALL treated patients: confirm eradication with a urea breath test, fecal antigen test, or biopsy-based test performed at least 4 weeks after finishing antibiotics and after holding PPIs/PCABs for at least 2 weeks (an H2-receptor antagonist may be used in the interim).