H. pylori Treatment
First-Line Treatment Recommendation
Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, achieving 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1, 2, 3
Standard Bismuth Quadruple Therapy Regimen
The regimen consists of four components taken for 14 days 1, 2, 3:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals on an empty stomach) 1, 2, 3
- Bismuth subsalicylate ~300 mg (or 262 mg as 2 tablets) four times daily 1, 2
- Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 2
- Tetracycline 500 mg four times daily 1, 2
Why bismuth quadruple therapy is preferred: This regimen is effective even against strains with dual resistance to clarithromycin and metronidazole due to bismuth's synergistic effect, and bacterial resistance to bismuth has never been described 1, 2. Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 1, 2.
Alternative First-Line Option When Bismuth is Unavailable
Concomitant non-bismuth quadruple therapy for 14 days 1, 2, 3:
- PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1, 2
- Amoxicillin 1000 mg twice daily 1, 2
- Clarithromycin 500 mg twice daily 1, 2
- Metronidazole 500 mg twice daily 1, 2
This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment 1.
Triple Therapy (Restricted Use Only)
Triple therapy should only be used in areas with documented clarithromycin resistance <15%, and even then, bismuth quadruple therapy is superior 1, 2. The FDA-approved triple therapy regimen consists of 4:
- PPI (lansoprazole 30 mg) twice daily 4
- Amoxicillin 1000 mg twice daily 4
- Clarithromycin 500 mg twice daily 4
- Duration: 14 days 1, 2
Critical Optimization Factors
PPI Dosing is Mandatory
High-dose PPI twice daily increases eradication efficacy by 6-10% compared to standard once-daily dosing 1, 2, 3. Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by an additional 8-12% compared to other PPIs 1, 2. The PPI must be taken 30 minutes before meals on an empty stomach, without concomitant use of other antacids 1, 2.
Treatment Duration Must Be 14 Days
Extending treatment from 7 to 14 days improves eradication success by approximately 5% 1, 2, 3. The 14-day duration is mandatory and cannot be shortened 1, 5.
Second-Line Treatment After First-Line Failure
After Failed Clarithromycin-Based Therapy
Use bismuth quadruple therapy for 14 days (if not previously used) 1, 2, 3. Never repeat clarithromycin if it was in the failed regimen, as resistance develops rapidly after exposure and eradication rates drop from 90% to 20% with resistant strains 1, 2.
After Failed Bismuth Quadruple Therapy
Levofloxacin-based triple therapy for 14 days (provided no prior fluoroquinolone exposure) 1, 2, 3:
- PPI (esomeprazole or rabeprazole 40 mg) twice daily 1, 2
- Amoxicillin 1000 mg twice daily 1, 2
- Levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 2
Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary) 1, 2.
Third-Line and Rescue Therapies
After Two Failed Eradication Attempts
Antibiotic susceptibility testing should guide further treatment whenever possible 1, 2, 3. Molecular testing for clarithromycin and levofloxacin resistance is available 1.
Rifabutin-Based Triple Therapy
Rifabutin triple therapy for 14 days is highly effective as rescue therapy after multiple treatment failures 1, 2, 3:
- Rifabutin 150 mg twice daily 1, 2
- Amoxicillin 1000 mg twice daily 1, 2
- PPI (esomeprazole or rabeprazole 40 mg) twice daily 1, 2
Rifabutin resistance is extremely rare, making it an effective rescue option 1, 2.
High-Dose Dual Amoxicillin-PPI Therapy
Alternative rescue therapy when other options have been exhausted 1, 2, 3:
- Amoxicillin 2-3 grams daily in 3-4 split doses 1, 2
- High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1, 2
- Duration: 14 days 1, 2
Special Populations
Patients with Penicillin Allergy
Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1, 2, 3. However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as most patients who report penicillin allergy are found not to have a true allergy 1.
If bismuth is unavailable, use clarithromycin plus metronidazole triple therapy (only in areas with clarithromycin resistance <15%) 1:
- PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
- Clarithromycin 500 mg twice daily 1
- Metronidazole 500 mg twice daily 1
- Duration: 14 days 1
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation 1, 2, 3. Never use serology to confirm eradication, as antibodies may persist long after successful treatment 1, 2.
Critical Pitfalls to Avoid
- Never assume low clarithromycin resistance without local surveillance data—most regions now have resistance rates >15-20% 1, 2
- Avoid repeating antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2
- Do not use standard-dose PPI once daily—always use high-dose twice-daily dosing 1, 2, 3
- Avoid concomitant use of other antacids with PPIs during treatment 1
- Do not use 7-10 day regimens—14 days is mandatory for optimal eradication 1, 2, 3, 5
Adjunctive Therapies
Probiotics can be used as adjunctive treatment to reduce antibiotic-associated diarrhea and improve patient compliance, but are of unproven benefit for improving eradication rates 1, 2. Diarrhea occurs in 21-41% of patients during the first week of therapy 2.