The American College of Gastroenterology (ACG) released updated clinical practice guidelines for the treatment of Helicobacter pylori infections.

Published in The American Journal of Gastroenterology, the guidelines provided new recommendations for first-line and salvage therapies based on rising antibiotic resistance rates and recently approved treatment regimens.

The guideline panel used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to systematically analyze 11 Population, Intervention, Comparison, and Outcome questions. Recommendations were generated based on quality of evidence, risks vs benefits, feasibility, and costs.

A comprehensive literature search was conducted including EMBASE, MEDLINE, Cochrane, ClinicalTrials.gov, and PubMed databases. The panel reviewed randomized controlled trials, systematic reviews, meta-analyses, and network meta-analyses.

Among the key recommendations were:

• Bismuth quadruple therapy (BQT) for 14 days as preferred first-line treatment when antibiotic susceptibility is unknown
• Rifabutin triple therapy or potassium-competitive acid blocker (PCAB) dual therapy for 14 days as suitable empiric alternatives in patients without penicillin allergy
• Avoiding clarithromycin- and levofloxacin-containing regimens without demonstrated susceptibility
• Universal posttreatment testing to confirm H pylori eradication at least 4 weeks after therapy completion
• Optimized BQT for 14 days as preferred salvage therapy in treatment-experienced patients who have not previously received the therapy.

The guidelines cited increasing rates of H pylori resistance to key antibiotics in North America. A meta-analysis of U.S. studies from 2011 to 2021 found resistance rates of 31.5% for clarithromycin, 37.5% for levofloxacin, and 22.2% for metronidazole.

Regional variations in resistance rates were observed:

• Northeast: Clarithromycin 32%, levofloxacin 31%, and metronidazole 21%
• Midwest: Clarithromycin 16%, levofloxacin 32%, and metronidazole 19%
• South: Clarithromycin 21%, levofloxacin 27%, and metronidazole 26%
• West: Clarithromycin 19%, levofloxacin 26%, and metronidazole 33%.

For treatment-naive patients, the guidelines strongly recommended optimized BQT for 14 days when antibiotic susceptibility is unknown. This regimen typically included:

• PPI (standard dose) twice daily
• Bismuth subcitrate (120 to 300 mg) or subsalicylate (300 mg) 4 times daily
• Tetracycline (500 mg) 4 times daily
• Metronidazole (500 mg) 3 to 4 times daily.

Two newly FDA-approved regimens were suggested as alternatives:

• Rifabutin triple therapy (Talicia): Omeprazole 10 mg, amoxicillin 250 mg, and rifabutin 12.5 mg; 4 capsules 3 times daily for 14 days
• PCAB dual therapy (Voquezna DualPak): Vonoprazan 20 mg twice daily and amoxicillin 1,000 mg 3 times daily for 14 days.

Treatment efficacy data was reported:

• Optimized BQT: 87% eradication rate in treatment-naive patients (n = 585)
• Rifabutin triple therapy: 77% eradication rate (95% confidence interval [CI] = 72%–82%) in treatment-naive patients
• PCAB-amoxicillin dual therapy: 77% eradication rate in overall population and 70% in clarithromycin-resistant strains.

Among treatment-experienced patients with persistent infection, the guidelines suggested:

• Optimized BQT for 14 days in those who have not previously received the therapy
• Rifabutin triple therapy for 14 days in those previously treated with optimized BQT
• Levofloxacin triple therapy only in patients with known levofloxacin-sensitive strains when other options are unavailable.

The guidelines emphasized avoiding repeated use of clarithromycin or levofloxacin without confirmed susceptibility.

Antibiotic susceptibility testing was advised for consideration in guiding therapy selection among treatment-experienced patients. Both culture-based and molecular methods, including PCR and next-generation sequencing, were noted as becoming increasingly available in the United States.

The guidelines strongly recommended posttreatment testing in all patients to confirm H pylori eradication. This was to be done with urea breath test, fecal antigen test, or biopsy-based testing at least 4 weeks following therapy completion. A meta-analysis reported recurrence rates of 1% (95% CI = 0.3%–3%) per year in the United States following successful eradication.

The guidelines also provided epidemiological data on H pylori prevalence:

• North American prevalence estimated at 30% to 40%
• A U.S. Veterans Health study (n = 913,328) found overall H pylori prevalence of 25.8%, with significant racial disparities: non-Hispanic White 20.1%, Hispanic 36.7%, and Black 40.2%
• Global H pylori prevalence declined from 58.2% (1980 to 1990) to 43.1% (2011 to 2020).

Indications for testing and treatment were outlined, including peptic ulcer disease, uninvestigated dyspepsia in patients younger than 60 years, functional dyspepsia, long-term NSAID or low-dose aspirin users, unexplained iron deficiency anemia, idiopathic thrombocytopenic purpura, and primary and secondary prevention of gastric adenocarcinoma in high-risk groups.

The guidelines highlighted the role of H pylori eradication in gastric cancer prevention. A meta-analysis showed a 46% reduction in gastric adenocarcinoma incidence with eradication. In a U.S. Veterans Health study, patients with confirmed H pylori eradication had a decreased risk of developing gastric adenocarcinoma (subhazard ratio = 0.24, 95% CI = 0.15–0.42).

The impact of CYP2C19 genotype on PPI metabolism and treatment efficacy was discussed. Esomeprazole or rabeprazole were recommended for rapid/ultrarapid CYP2C19 metabolizers.

A meta-analysis on probiotic supplementation showed a modest benefit (risk ratio = 1.10, 95% CI = 1.10–1.18) in eradication rates.

The guideline panel identified key knowledge gaps as research priorities, including optimal use of antibiotic susceptibility testing in clinical practice, comparative effectiveness of new FDA-approved regimens in North American populations, and evaluation of PCAB-based therapies as salvage treatment options.

Conflict of interest disclosures can be found in the guidelines.