H. pylori Treatment
First-Line Treatment Recommendation
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth 300mg four times daily, metronidazole 500mg three to four times daily (total 1.5-2g/day), and tetracycline 500mg four times daily. 1, 2
Specific Dosing Details
- PPI dosing: Standard dose twice daily (pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, or rabeprazole 20mg), taken 30 minutes before meals on an empty stomach 1, 3
- Bismuth: Bismuth subsalicylate 262mg (2 tablets) or bismuth subcitrate 120mg, four times daily 4, 1
- Metronidazole: 500mg three to four times daily (total daily dose 1.5-2g) 1, 2
- Tetracycline: 500mg four times daily 1, 2
- Duration: 14 days is mandatory, as this improves eradication by approximately 5% compared to 7-10 day regimens 4, 1, 3
Why This Regimen Works
Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect, and no bacterial resistance to bismuth has been described 1, 2. This regimen is effective regardless of clarithromycin resistance patterns, which now exceed 15-20% in most of North America and Europe 3, 2.
Alternative First-Line When Bismuth Unavailable
Concomitant non-bismuth quadruple therapy for 14 days is the preferred alternative: PPI twice daily + amoxicillin 1000mg twice daily + clarithromycin 500mg twice daily + metronidazole 500mg twice daily 1, 3, 2. This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment 3.
Special Population: Penicillin Allergy
Bismuth quadruple therapy is the first choice in patients with penicillin allergy, as it contains tetracycline instead of amoxicillin 4, 1, 2.
Second-Line Treatment After First Failure
The choice depends on what was used first-line:
- If clarithromycin-based therapy failed: Use bismuth quadruple therapy for 14 days (if not previously used) 1, 2
- If bismuth quadruple therapy failed: Use levofloxacin triple therapy for 14 days: PPI twice daily + amoxicillin 1000mg twice daily + levofloxacin 500mg once daily (or 250mg twice daily) 4, 1, 2
Critical Antibiotic Reuse Rules
- Never reuse clarithromycin or levofloxacin after exposure, as resistance develops rapidly 4, 1, 2
- Amoxicillin and tetracycline can be reused because resistance remains rare (<5%) 1, 2
- Metronidazole can be reused with bismuth due to bismuth's synergistic effect that overcomes in vitro resistance 4, 2
Third-Line and Rescue Therapies
After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible. 4, 1, 3, 2 If susceptibility testing is unavailable:
- Rifabutin triple therapy for 14 days: Rifabutin 150mg twice daily (or 300mg once daily) + amoxicillin 1000mg twice daily + PPI twice daily 4, 1, 2
- High-dose dual therapy for 14 days: Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily (rabeprazole 20mg four times daily or double-dose esomeprazole/rabeprazole 40mg twice daily) 4, 1, 2
Rifabutin resistance is extremely rare, making it highly effective as rescue therapy after multiple treatment failures 1, 3.
Critical Optimization Factors
PPI Optimization
High-dose PPI twice daily is mandatory and increases eradication efficacy by 6-10% compared to standard once-daily dosing. 3, 2 Esomeprazole or rabeprazole 40mg twice daily may increase cure rates by an additional 8-12% compared to other PPIs 1, 3. PPIs must be taken 30 minutes before meals on an empty stomach, without concomitant use of other antacids 1, 2.
Treatment Duration
14 days is superior to 7-10 day regimens across all treatment options 4, 1, 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, 3, 2 Never use serology to confirm eradication, as antibodies may persist long after successful treatment 2.
Common Pitfalls to Avoid
- Do not use clarithromycin-based triple therapy without knowing local resistance patterns—clarithromycin resistance now exceeds 15% in most regions, making traditional triple therapy achieve only 70% eradication rates 3, 2
- Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary) 3, 2
- Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 3
- Do not use standard-dose PPI once daily—this is inadequate for optimal eradication 3, 2
- Do not repeat clarithromycin if the patient has prior macrolide exposure for any indication, as cross-resistance is universal within the macrolide family 3
Adjunctive Therapies
Probiotics can be used to reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve patient compliance, but they do not significantly increase eradication rates 3, 2, 5.