H. pylori Eradication Regimens: Dosages and Durations
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in most clinical scenarios, achieving 80–90% eradication rates even in areas with high clarithromycin resistance. 1, 2
First-Line Treatment Regimens
Bismuth Quadruple Therapy (Preferred First-Line)
This regimen is recommended as the primary first-line option for all adults with H. pylori infection. 1, 2
Components and dosing:
- PPI twice daily (esomeprazole 40 mg or rabeprazole 40 mg preferred; alternatives: omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) 1, 2
- Bismuth subsalicylate 262 mg (2 tablets) four times daily OR bismuth subcitrate 120 mg four times daily 1, 2
- Metronidazole 500 mg three to four times daily (total 1.5–2 g/day) 3, 1, 2
- Tetracycline 500 mg four times daily 1, 2
- Duration: 14 days 1, 2, 4
Key advantages: Bismuth quadruple therapy achieves 80–90% eradication even with dual clarithromycin-metronidazole resistance because no bacterial resistance to bismuth has been described, and bismuth's synergistic effect overcomes metronidazole resistance in vitro. 1, 2 Tetracycline resistance remains rare (<5%). 1
Concomitant Non-Bismuth Quadruple Therapy (Alternative First-Line)
Use this regimen only in areas with documented clarithromycin resistance <15% or when bismuth is unavailable. 1, 4
Components and dosing:
- PPI twice daily (esomeprazole 40 mg or rabeprazole 40 mg preferred) 1
- Amoxicillin 1000 mg twice daily 1, 4
- Clarithromycin 500 mg twice daily 1, 4
- Metronidazole 500 mg twice daily 1, 4
- Duration: 14 days 1, 4
Critical caveat: Standard triple therapy (PPI + clarithromycin + amoxicillin) should be abandoned when regional clarithromycin resistance exceeds 15–20%, as eradication rates drop to approximately 70% or lower. 1, 5 Clarithromycin resistance now exceeds 15% in most of North America and Central, Western, and Southern Europe. 1
Second-Line Treatment (After First-Line Failure)
After Clarithromycin-Based Therapy Fails
Bismuth quadruple therapy for 14 days (if not used first-line) 1, 2, 4
Alternative: Levofloxacin triple therapy (only if no prior fluoroquinolone exposure):
- PPI twice daily (esomeprazole 40 mg or rabeprazole 40 mg preferred) 1, 2
- Amoxicillin 1000 mg twice daily 1, 2
- Levofloxacin 500 mg once daily OR 250 mg twice daily 1, 2
- Duration: 14 days 1, 2
Never reuse clarithromycin if it was in the failed regimen—resistance develops rapidly after exposure, dropping eradication rates from 90% to 20% with resistant strains. 1, 2
After Bismuth Quadruple Therapy Fails
Levofloxacin triple therapy for 14 days (provided no prior fluoroquinolone exposure) 1, 2
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 2, 4
Rifabutin Triple Therapy (Third-Line)
Components and dosing:
- PPI twice daily (esomeprazole 40 mg or rabeprazole 40 mg preferred) 1, 2
- Rifabutin 150 mg twice daily OR 300 mg once daily 1, 2
- Amoxicillin 1000 mg twice daily 1, 2
- Duration: 14 days 1, 2
Reserve rifabutin for patients who have failed at least two prior regimens—resistance to rifabutin remains rare. 1
High-Dose Dual Therapy (Rescue Option)
Components and dosing:
- Amoxicillin 2–3 grams daily divided into 3–4 doses 3, 1, 2
- PPI high-dose twice daily (esomeprazole 40 mg or rabeprazole 40 mg) 1, 2
- Duration: 14 days 1, 2
Critical Optimization Factors
PPI Dosing and Timing
High-dose PPI twice daily is mandatory—standard once-daily dosing significantly reduces treatment efficacy. 3, 1, 5 Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8–12% compared to other PPIs. 1, 5
Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids. 1, 2
Treatment Duration
All regimens must be given for 14 days—extending therapy from 7 to 14 days improves eradication success by approximately 5%. 3, 1, 2, 5, 4 The Toronto Consensus, Maastricht V/Florence, and American College of Gastroenterology all endorse 14 days as the standard duration. 1, 4
Antibiotic Reuse Rules
Never reuse:
- Clarithromycin or levofloxacin if they were in a failed regimen—resistance develops rapidly after exposure. 1, 2
Can be reused:
- Amoxicillin and tetracycline—resistance remains rare (<5%). 1, 2
- Metronidazole with bismuth—bismuth's synergistic effect overcomes metronidazole resistance. 3, 1
Special Populations
Penicillin Allergy
Bismuth quadruple therapy is the first choice because it contains tetracycline instead of amoxicillin. 1, 2
Consider penicillin allergy testing after first-line failure—most patients with documented penicillin allergy do not have true anaphylaxis, and delisting the allergy enables amoxicillin use. 3, 2
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after stopping PPIs. 1, 2, 5
Never use serology to confirm eradication—antibodies persist long after successful treatment. 1, 5
Common Pitfalls to Avoid
- Do not use standard-dose PPI once daily—this is a major cause of treatment failure. 1, 5
- Do not shorten therapy below 14 days—this reduces eradication success. 1, 2, 4
- Do not repeat the same regimen—this guarantees failure and accelerates resistance. 1, 2
- Do not use clarithromycin-based triple therapy empirically in areas with clarithromycin resistance ≥15%—eradication rates are unacceptably low. 1, 5
- Do not use levofloxacin as first-line therapy—this accelerates resistance development and eliminates a valuable rescue option. 1
- Avoid pantoprazole when possible—its acid-suppression potency is markedly lower (40 mg pantoprazole ≈ 9 mg omeprazole equivalent). 1