H. pylori Eradication Treatment
Bismuth-containing quadruple therapy for 14 days is the preferred first-line treatment for H. pylori eradication in most clinical settings, particularly in areas with high clarithromycin resistance (>15-20%). 1, 2
First-Line Treatment Regimen
Bismuth quadruple therapy should be prescribed as follows:
- High-dose PPI (rabeprazole 40 mg or esomeprazole 40 mg twice daily—NOT pantoprazole) 1
- Bismuth subcitrate 1
- Tetracycline 1
- Metronidazole 1
- Duration: 14 days (achieves >80% eradication rates even with antibiotic resistance) 1
This regimen is recommended by the American Gastroenterological Association as the preferred empirical first-line treatment because clarithromycin resistance now exceeds 15-20% in most regions. 1, 2
Alternative First-Line Option (Low Clarithromycin Resistance Areas Only)
If local clarithromycin resistance is documented <15%, triple therapy may be used:
- PPI (high-dose: esomeprazole or rabeprazole 40 mg twice daily) + clarithromycin + amoxicillin for 14 days 2, 3
- This combination achieved 69-83% eradication rates in clinical trials 3
- Extending treatment from 7 to 14 days improves eradication by approximately 5% 2
Critical caveat: Triple therapy with clarithromycin should NOT be used empirically in most U.S. settings due to high resistance rates. 1, 2
Second-Line Treatment (After First-Line Failure)
If bismuth quadruple therapy was NOT used initially:
If bismuth quadruple therapy was already used:
- Levofloxacin-containing triple therapy (PPI + levofloxacin + amoxicillin) for 14 days 1, 2
- Important: Rising levofloxacin resistance rates must be considered; local surveillance data should guide this decision 2, 4
Never reuse antibiotics from the first-line regimen to prevent resistance. 1, 2
Third-Line Treatment (After Two Failures)
Antimicrobial susceptibility testing should guide treatment whenever possible. 2, 5
If susceptibility testing is unavailable:
- Rifabutin triple therapy for 14 days 2
- Alternative antibiotics not previously used: tetracycline, furazolidone, or high-dose PPI/amoxicillin 5, 4, 6
Special Population: Penicillin Allergy
In areas of high clarithromycin resistance:
- Bismuth-containing quadruple therapy (no penicillin component) 2
In areas of low clarithromycin resistance:
- PPI + clarithromycin + metronidazole 2
Confirmation of Eradication
Testing MUST be performed at least 4 weeks after completing treatment. 1, 2
Preferred non-invasive tests:
- Urea breath test (13C-UBT) - gold standard 1, 2
- Laboratory-based validated monoclonal stool antigen test - alternative 1, 2
Critical testing precautions to avoid false-negative results:
- Discontinue PPIs at least 2 weeks before testing 1
- Discontinue antibiotics at least 4 weeks before testing 1
- Discontinue sucralfate at least 4 weeks before testing 1, 2
Critical Indications for H. pylori Eradication
Mandatory eradication in:
- All patients with peptic ulcer disease (active or history) 1, 2, 7
- Patients with peptic ulcer history before starting or continuing NSAIDs 1, 7
- First-degree relatives of gastric cancer patients 2, 4
- Patients with gastric MALT lymphoma 4
- Patients with previous gastric neoplasia treated endoscopically 2
Post-Eradication PPI Management
For uncomplicated duodenal ulcer:
- Prolonged PPI after eradication is NOT recommended 1
- Eradication eliminates the need for maintenance PPI therapy 1
For gastric ulcer and complicated duodenal ulcer:
- Continue PPI until complete healing is confirmed by endoscopy 1
For bleeding ulcers:
- Start eradication therapy when oral feeding is reintroduced 1
Key Success Factors
Patient compliance is the most critical factor for successful eradication. 1, 2
- Ensure patients understand the importance of completing the full 14-day course 1
- Antibiotic resistance is the primary reason for treatment failure 2, 5, 4
- Never use mono-antibiotic therapy, which promotes resistance 1
Clinical outcome data: