H. Pylori Treatment
First-Line Therapy: Bismuth Quadruple Therapy for 14 Days
Bismuth quadruple therapy for 14 days is the definitive first-line treatment for adults with confirmed H. pylori infection, achieving 80–90% eradication rates even in regions with high clarithromycin and metronidazole resistance. 1, 2, 3
Recommended Regimen Components
- Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs; increases cure rates by 8–12%) 1, 2, 3
- Bismuth subsalicylate 262 mg (two tablets) four times daily 1, 2, 3
- Metronidazole 500 mg three to four times daily (total 1.5–2 g/day) 1, 2, 3
- Tetracycline 500 mg four times daily 1, 2, 3
Critical Administration Instructions
- Take PPI 30 minutes before meals on an empty stomach; avoid concomitant antacids 1, 2, 3
- Take bismuth 30 minutes before meals and at bedtime 2
- Take metronidazole 30 minutes after meals 2
- 14-day duration is mandatory—extending from 7 to 14 days improves eradication by approximately 5% 1, 2, 3, 4
Why Bismuth Quadruple Therapy Is First-Line
Clarithromycin resistance now exceeds 15–20% across North America and Europe, reducing traditional triple therapy success to only ~70% 1, 3. When clarithromycin-resistant strains are present, triple therapy eradication drops from ~90% to ~20% 1, 3. In contrast, bismuth quadruple therapy maintains 80–90% efficacy even against dual clarithromycin-metronidazole resistant strains because bismuth's synergistic effect overcomes metronidazole resistance in vitro 5, 1, 3, 6. Additionally, no bacterial resistance to bismuth has been described, and tetracycline resistance remains rare (<5%) 1, 3.
Alternative First-Line Option (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy may be used only if bismuth is unavailable AND local clarithromycin resistance is documented <15%. 1, 2, 3
- 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
- Duration: 14 days 1, 4
Do not use clarithromycin-based triple therapy empirically unless local surveillance confirms resistance <15%—most regions now exceed this threshold 1, 3.
Second-Line Therapy After First-Line Failure
After Bismuth Quadruple Therapy Fails
Levofloxacin triple therapy for 14 days is the recommended second-line option, provided the patient has no prior fluoroquinolone exposure. 5, 1, 2, 3
- Esomeprazole or rabeprazole 40 mg twice daily 1
- Amoxicillin 1000 mg twice daily 5, 1
- Levofloxacin 500 mg once daily (or 250 mg twice daily) 5, 1
- Duration: 14 days 1
Critical caveat: Levofloxacin resistance is rising globally (primary 11–30%, secondary 19–30%) 1, 3. Never use levofloxacin in patients with chronic bronchopneumopathy or any prior fluoroquinolone exposure for any indication, as cross-resistance is universal 5, 1.
After Clarithromycin-Based Triple Therapy Fails
Switch to bismuth quadruple therapy for 14 days. 1, 2, 3 Never repeat clarithromycin if it was in the failed regimen—resistance develops rapidly after exposure, dropping eradication from ~90% to ~20% 1, 3.
Third-Line and Rescue Therapies
After two documented treatment failures with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment whenever possible. 5, 1, 2, 3
Empiric Third-Line Options (When Susceptibility Testing Unavailable)
Rifabutin triple therapy for 14 days:
- Rifabutin 150 mg twice daily 1, 2, 3
- Amoxicillin 1000 mg twice daily 1, 2, 3
- Esomeprazole or rabeprazole 40 mg twice daily 1, 2, 3
Rifabutin resistance is rare, making this an effective rescue option 1, 3. However, reserve rifabutin for at least third-line due to potential myelotoxicity 4.
High-dose dual therapy for 14 days (alternative rescue):
- Amoxicillin 2–3 g daily in 3–4 divided doses 1, 2, 3
- Esomeprazole or rabeprazole 40 mg twice daily 1, 2, 3
This simpler regimen may be useful in elderly or complex patients 2, 3.
Special Populations: Penicillin Allergy
In patients with confirmed penicillin allergy, bismuth quadruple therapy is the first-choice regimen because it contains tetracycline instead of amoxicillin. 5, 1, 2, 3
Consider penicillin allergy testing after first-line failure—most reported allergies are not true, and amoxicillin resistance remains rare (<5%) 1, 2, 3.
If bismuth is unavailable and clarithromycin resistance is <15%:
- PPI + clarithromycin + metronidazole for 14 days 5
For second-line in penicillin-allergic patients (if no prior fluoroquinolone exposure):
- PPI + clarithromycin + levofloxacin for 14 days 5
Confirmation of Eradication (Test-of-Cure)
Perform urea breath test or validated monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after stopping PPI. 1, 2, 3
Never use serology for test-of-cure—antibodies persist long after successful eradication 1, 3.
Patient Factors That Reduce Success
- Smoking roughly doubles the odds of treatment failure (OR ≈1.95); advise cessation during therapy 1, 2
- Elevated BMI/obesity may lower gastric mucosal drug concentrations, potentially reducing efficacy 1, 2
- Poor compliance is a leading cause of failure; provide clear written instructions and emphasize completing the full 14-day course 1, 2, 3
Expected Side Effects
Diarrhea occurs in 21–41% of patients during the first week due to gut microbiota disruption; this does not indicate treatment failure 1. Consider adjunctive probiotics to reduce diarrhea risk and improve compliance 1.
Critical Pitfalls to Avoid
- Never use once-daily PPI dosing—it is a major cause of treatment failure 1, 2, 3
- Avoid pantoprazole (40 mg provides acid suppression equivalent to only ~9 mg omeprazole) 1, 3
- Do not shorten therapy below 14 days—this reduces eradication by ~5% 1, 2, 3, 4
- Never repeat clarithromycin or levofloxacin if they were in a failed regimen 1, 2, 3
- Do not assume low clarithromycin resistance without local surveillance data—most regions now exceed 15–20% 1, 3
- Do not use levofloxacin empirically as first-line therapy—this accelerates resistance development 1, 3