What is the recommended treatment for H pylori (Helicobacter pylori) infection?

H. pylori Treatment

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a high-dose PPI (twice daily), bismuth subsalicylate, tetracycline, and metronidazole. 1, 2

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to the synergistic effect of bismuth with other antibiotics. 1, 2 This regimen is preferred because:

• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective with eradication rates dropping to approximately 70%—well below the 80% minimum target. 2, 3
• Bismuth resistance is extremely rare, making this regimen effective even against antibiotic-resistant strains 1, 2
• The regimen uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 3

Specific Dosing for Bismuth Quadruple Therapy

• PPI (e.g., omeprazole 40 mg or esomeprazole 40 mg) twice daily 1, 2
• Bismuth subsalicylate 525 mg four times daily 1, 2
• Tetracycline 500 mg four times daily 1, 2
• Metronidazole 500 mg three times daily (or 1.5-2 g daily in divided doses for improved efficacy) 1, 3
• Duration: 14 days 1, 2

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available. 2, 3 This consists of:

• PPI twice daily 2, 3
• Amoxicillin 1000 mg twice daily 2, 3, 4
• Clarithromycin 500 mg twice daily 2, 3
• Metronidazole 500 mg twice daily 2, 3

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing the development of resistance during treatment. 3

Critical Optimization Strategies

PPI Dosing is Crucial

High-dose PPI (twice daily) significantly increases eradication efficacy by 6-10% compared to standard doses by reducing gastric acidity and enhancing antibiotic activity. 1, 2

• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% 3
• Standard-dose PPI once daily is inadequate—always use twice-daily dosing 3
• Confirm that patients are taking the PPI correctly (30-60 minutes before meals) to maximize absorption and activation 1

Treatment Duration Matters

Extending treatment duration to 14 days improves eradication success by approximately 5% compared to shorter regimens. 1, 2, 5

Second-Line Treatment After First-Line Failure

After failure of first-line therapy, choose based on what was previously used:

If Bismuth Quadruple Therapy Failed First

Levofloxacin-based triple therapy for 14 days: 1, 2

• PPI twice daily 2
• Amoxicillin 1000 mg twice daily 2, 4
• Levofloxacin 500 mg once daily (or 250 mg twice daily) 2

However, rising rates of levofloxacin resistance (11-30% primary, 19-30% secondary) should be taken into account—do not use levofloxacin empirically as first-line therapy. 3

If Non-Bismuth Therapy Failed First

Use bismuth quadruple therapy for 14 days as described above. 1, 2

Third-Line and Rescue Therapies

After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 2, 6

When susceptibility testing is not available:

• Rifabutin-based triple therapy for 14 days is highly effective as a rescue option after multiple treatment failures: rifabutin 150 mg twice daily, amoxicillin 1000 mg twice daily, and PPI twice daily 1, 3, 4
• Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections 1
• Rifabutin should be reserved for patients who have failed at least 2-3 prior eradication attempts 1, 3

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2

• Serology should not be used to confirm eradication as antibodies may persist long after successful treatment 1, 2

Critical Pitfalls and Caveats

Avoid Repeating Previously Used Antibiotics

Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, to maximize the probability of successful eradication. 1, 2, 3

• If the patient has had previous exposure to clarithromycin for any indication (not just H. pylori), avoid using it in the current regimen due to cross-resistance within the macrolide family 3

Regional Resistance Patterns Matter

Never assume low clarithromycin resistance without local surveillance data—most regions now have resistance rates exceeding 15-20%. 2, 3

• When H. pylori strains are clarithromycin-resistant, eradication rates drop to approximately 20% compared to 90% with susceptible strains 3
• PPI-clarithromycin-containing triple therapy should be abandoned when regional clarithromycin resistance exceeds 15-20% 2, 3

Patient-Specific Factors

Smoking is a risk factor for treatment failure, with an odds ratio of 1.95 for eradication failure among smokers versus non-smokers. 3

High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level. 3

Penicillin Allergy Considerations

• For patients with penicillin allergy who cannot take amoxicillin, metronidazole can be substituted in triple therapy regimens 3
• Do not assume penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 3

Managing Side Effects

Diarrhea occurs in 21-41% of patients during the first week of H. pylori eradication therapy due to disruption of normal gut microbiota. 3

• Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance 3, 6
• Probiotics can help reduce side effects, though evidence for increased eradication rates is limited 2, 6