H. pylori Management
First-Line Treatment: Bismuth Quadruple Therapy
Bismuth quadruple therapy for 14 days is the definitive first-line treatment for confirmed H. pylori infection, achieving 80–90% eradication rates even in regions with high clarithromycin resistance (>15%). 1
Standard Regimen Components
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred; increases cure rates by 8–12% compared to standard PPIs), taken 30 minutes before meals on an empty stomach 1
- Bismuth subsalicylate 262 mg (two tablets) four times daily or bismuth subcitrate 120 mg four times daily, taken 30 minutes before meals and at bedtime 1
- Metronidazole 500 mg three to four times daily (total 1.5–2 g daily), taken 30 minutes after meals 1
- Tetracycline 500 mg four times daily (do not substitute doxycycline—significantly inferior results) 1, 2
Treatment Duration
- 14 days is mandatory; extending from 7–10 days to 14 days improves eradication by approximately 5% 1
Why This Regimen Works
- Bismuth has no described bacterial resistance and exerts synergistic effects that overcome metronidazole resistance in vitro 1
- Effective against strains with dual resistance to clarithromycin and metronidazole 1
- Uses antibiotics from the WHO "Access group" (tetracycline, metronidazole) rather than "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 1
Alternative First-Line Regimen (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy for 14 days may be used only in regions with documented clarithromycin resistance <15%: 1
- High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
- Amoxicillin 1000 mg twice daily 1
- Clarithromycin 500 mg twice daily 1
- Metronidazole 500 mg twice daily 1
Critical caveat: Standard clarithromycin-containing triple therapy should be abandoned when regional clarithromycin resistance exceeds 15–20%, as eradication rates drop from 90% to approximately 20% with resistant strains 1
Special Population: Penicillin Allergy
Bismuth quadruple therapy is the first-choice regimen because it contains tetracycline rather than amoxicillin 1
- Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as most reported allergies are not true allergies 1
- If bismuth unavailable and allergy confirmed: PPI + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days (only in areas with clarithromycin resistance <15%) 1
Second-Line Treatment After First-Line Failure
After Clarithromycin-Based Therapy Fails
Bismuth quadruple therapy for 14 days (if not previously used) 1
After Bismuth Quadruple Therapy Fails
Levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure): 1
- High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
- Amoxicillin 1000 mg twice daily 1
- Levofloxacin 500 mg once daily 1
Critical pitfall: Never use levofloxacin in patients with chronic bronchopneumopathy or prior fluoroquinolone exposure for any indication—cross-resistance exists within the fluoroquinolone family 1
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1
Rifabutin Triple Therapy (14 days)
- Rifabutin 150 mg twice daily 1
- Amoxicillin 1000 mg twice daily 1
- High-dose PPI twice daily 1
- Rifabutin resistance is rare; reserve for third/fourth-line therapy 1
High-Dose Dual Therapy (14 days)
- Amoxicillin 2–3 g daily in 3–4 split doses 1
- High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
- Alternative rescue option when other regimens exhausted 1
Post-Treatment Eradication Testing
Confirm eradication with urea breath test or validated monoclonal stool antigen test at least 4 weeks after completion of therapy. 3
Testing Requirements
- Discontinue PPI at least 2 weeks before testing (preferably 7–14 days) to avoid false-negative results 3
- Discontinue antibiotics and bismuth at least 4 weeks before testing 3
- Fast for at least 6 hours before testing 3
- Never use serology to confirm eradication—antibodies persist long after successful treatment 1
Mandatory Testing Populations
- All patients with gastric ulcer (requires endoscopic follow-up to ensure complete healing) 3
- Complicated peptic ulcer disease 3
- Low-grade gastric MALT lymphoma 3
- After treatment failure 3
Critical Optimization Factors
PPI Selection and Dosing
- Esomeprazole or rabeprazole 40 mg twice daily strongly preferred over other PPIs 1
- Avoid pantoprazole—40 mg provides acid-suppression potency equivalent to only 9 mg omeprazole 1
- Standard once-daily PPI dosing is inadequate and a major cause of treatment failure 1
Antibiotic Reuse Principles
- Never repeat clarithromycin or levofloxacin if they were in a failed regimen—resistance develops rapidly after exposure 1
- Metronidazole can be reused with bismuth due to synergistic effects 1
- Amoxicillin and tetracycline can be reused because resistance remains rare (<5%) 1
Patient Factors Affecting Success
- Smoking increases risk of failure (odds ratio 1.95) 1
- High BMI/obesity increases risk due to lower drug concentrations at gastric mucosal level 1
- Poor compliance (>10% of patients) leads to much lower eradication rates—provide clear education on rationale, dosing, expected adverse events, and importance of completing full course 1
Common Pitfalls to Avoid
- Do not assume low clarithromycin resistance without local surveillance data—most regions now have resistance >15–20% 1
- Do not use concomitant, sequential, or hybrid therapies—they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1
- Do not shorten therapy below 14 days 1
- Do not substitute doxycycline for tetracycline—multiple studies show significantly inferior results 1, 2
- Do not test for eradication before 4 weeks—false-negative results occur due to temporary bacterial suppression 3