Summary

ACG 2024 guideline on H. pylori treatment in North America, replacing the 2017 version in response to rising clarithromycin/levofloxacin resistance and FDA approval of vonoprazan-based regimens. Bismuth quadruple therapy (BQT) for 14 days is preferred first-line when susceptibility is unknown; rifabutin triple therapy or vonoprazan-amoxicillin dual therapy are alternatives. Clarithromycin- and levofloxacin-containing regimens should be reserved for cases with documented susceptibility. Universal post-treatment test of cure is required.

Key Recommendations

First-line for treatment-naive patients with unknown susceptibility: optimized bismuth quadruple therapy (BQT) for 14 days.
Suitable empiric first-line alternatives in non-penicillin-allergic patients: rifabutin triple therapy or PCAB (vonoprazan)-amoxicillin dual therapy for 14 days.
Do not use clarithromycin- or levofloxacin-containing regimens empirically; reserve for patients with documented susceptibility.
If clarithromycin must be used empirically (no macrolide history, no other option), prefer PCAB-clarithromycin-amoxicillin triple over PPI-clarithromycin triple, given for 14 days.
Do not recommend PPI-clarithromycin triple therapy as first-line due to >20-30% US clarithromycin resistance.
Test all patients for cure ≥4 weeks after therapy using urea breath test or fecal antigen; stop PPI 2 weeks prior; do not use serology.
For treatment-experienced patients not previously given optimized BQT: optimized BQT for 14 days is preferred salvage.
For patients failing optimized BQT: rifabutin triple therapy for 14 days is the preferred salvage option.
Test-and-treat strategy for uninvestigated dyspepsia is appropriate in patients <60 yr without alarm features (consider <50 yr in higher-risk populations).
Test and treat H. pylori in: PUD (current/past), MALT lymphoma, ITP, unexplained iron deficiency, long-term NSAID/aspirin users, household contacts of H. pylori-positive individuals, autoimmune gastritis, gastric premalignant conditions, and resected early gastric cancer.
Obtain antibiotic susceptibility testing before considering clarithromycin- or levofloxacin-containing salvage regimens.
Substitute doxycycline for tetracycline only when unavoidable—eradication rates are substantially lower; do not use H2RAs in eradication regimens.

Thresholds & Doses

Optimized BQT (14 days): bismuth ≥300 mg QID; metronidazole 1.5–2 g/day in 3–4 divided doses; tetracycline 500 mg QID; standard-dose PPI BID.
Rifabutin triple therapy (14 days): omeprazole 40 mg + rifabutin 50 mg + amoxicillin 1 g, each given every 8 hours (Talicia); alternatively rifabutin 150 mg BID.
Vonoprazan-amoxicillin dual therapy (14 days): vonoprazan 20 mg BID + amoxicillin 1,000 mg TID.
Vonoprazan-clarithromycin triple therapy (14 days, if used): vonoprazan 20 mg + clarithromycin 500 mg + amoxicillin 1,000 mg, all BID.
All recommended regimens: 14-day duration preferred over 10 or 7 days.
Test of cure: ≥4 weeks after completing therapy; hold PPI ×2 weeks, hold bismuth/antibiotics ×4 weeks before testing.
Test-and-treat for uninvestigated dyspepsia: age <60 yr (or <50 yr in higher-risk populations) without alarm features.
US H. pylori antibiotic resistance: clarithromycin 20–30%, levofloxacin ~40%, metronidazole high; amoxicillin/tetracycline/rifabutin <5%.
Target local first-line eradication rate >85%; consider susceptibility testing if rates fall below this threshold.
For CYP2C19 rapid/ultrarapid metabolizers on omeprazole/lansoprazole/pantoprazole: increase PPI dose 50–100%, or switch to esomeprazole/rabeprazole or a PCAB.

Citations

Table 5 — Recommended regimens for treatment-naive patients with H. pylori infection
Table 6 — Recommended salvage regimens for treatment-experienced patients with persistent H. pylori infection
Table 4 — Indications for H. pylori testing and treatment
Figure 1 — Empiric first-line regimens algorithm for treatment-naive patients
Figures 3 and 4 — Empiric and susceptibility-guided salvage regimen algorithms
Section: Post-treatment testing for cure — Key concept on universal test of cure with UBT/fecal antigen ≥4 weeks after therapy
Section: Antibiotic susceptibility testing — Key concept on tailored vs empiric therapy
Summary of recommendations for treatment-naive and treatment-experienced patients