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Helicobacter pylori is a prevalent, global infectious disease that causes dyspepsia, peptic ulcer disease, and gastric cancer. The American College of Gastroenterology commissioned this clinical practice guideline (CPG) to inform the evidence-based management of patients with H. pylori infection in North America. This CPG used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to systematically analyze 11 Population, Intervention, Comparison, and Outcome questions and generate recommendations. Where evidence was insufficient or the topic did not lend itself to GRADE, expert consensus was used to create 6 key concepts. For treatment-naive patients with H. pylori infection, bismuth quadruple therapy (BQT) for 14 days is the preferred regimen when antibiotic susceptibility is unknown. Rifabutin triple therapy or potassium-competitive acid blocker dual therapy for 14 days is a suitable empiric alternative in patients without penicillin allergy. In treatment-experienced patients with persistent H. pylori infection, "optimized" BQT for 14 days is preferred for those who have not been treated with optimized BQT previously and for whom antibiotic susceptibility is unknown. In patients previously treated with optimized BQT, rifabutin triple therapy for 14 days is a suitable empiric alternative. Salvage regimens containing clarithromycin or levofloxacin should only be used if antibiotic susceptibility is confirmed. The CPG also addresses who to test, the need for universal post-treatment test-of-cure, and the current evidence regarding antibiotic susceptibility testing and its role in guiding the choice of initial and salvage treatment. The CPG concludes with a discussion of proposed research priorities to address knowledge gaps and inform future management recommendations in patients with H. pylori infection from North America.

Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.