H. pylori Treatment
First-Line Treatment: Bismuth Quadruple Therapy
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 antibiotic resistance. 1, 2
The regimen consists of:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals) 1, 2
- Bismuth subsalicylate ~300 mg four times daily 1, 2
- Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 3
- Tetracycline 500 mg four times daily 1, 2
Why Bismuth Quadruple Therapy is Preferred
- No bacterial resistance to bismuth has been described, making this regimen highly reliable 1
- Effective against metronidazole-resistant strains due to bismuth's synergistic effect with other antibiotics 1, 2
- Uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 1
- Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy unacceptably ineffective 1, 2
Critical Optimization Factors
- 14-day duration is mandatory—this improves eradication by approximately 5% compared to 7-10 day regimens 1, 2
- High-dose PPI twice daily increases efficacy by 6-10% compared to standard once-daily dosing 1, 2
- Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by an additional 8-12% compared to other PPIs 1, 2
Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy
When bismuth is unavailable, concomitant non-bismuth quadruple therapy is the preferred alternative, consisting of all four drugs given simultaneously for 14 days. 1, 2
The regimen consists of:
- PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
- Amoxicillin 1000 mg twice daily 1, 4
- Clarithromycin 500 mg twice daily 1
- Metronidazole 500 mg twice daily 1, 3
Important Caveats
- Only use in areas with documented clarithromycin resistance <15%—most regions now exceed this threshold 1, 2
- Avoid sequential therapy—giving all antibiotics simultaneously prevents resistance development during treatment 1
- Never assume low clarithromycin resistance without local surveillance data 1
Second-Line Treatment After First-Line Failure
If Bismuth Quadruple Therapy Was Not Used First-Line
Use bismuth quadruple therapy for 14 days as described above. 1, 2
If Bismuth Quadruple Therapy Has Already Failed
Levofloxacin-based triple therapy is recommended if the patient has no prior fluoroquinolone exposure. 1, 2
The regimen consists of:
- PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
- Amoxicillin 1000 mg twice daily 1, 4
- Levofloxacin 500 mg once daily (or 250 mg twice daily) for 14 days 1, 2
Critical Warnings About Levofloxacin
- Do not use levofloxacin empirically as first-line therapy—this accelerates resistance development 1, 2
- Levofloxacin resistance rates are rapidly increasing (11-30% primary, 19-30% secondary) 1
- The FDA recommends fluoroquinolones be used as a last choice due to risk of serious side effects 1
- Never use in patients with prior fluoroquinolone exposure for any indication (e.g., chronic bronchopneumopathy) 1
What NOT to Do After First-Line Failure
- Never repeat clarithromycin if it was in the failed regimen—resistance develops rapidly after exposure, with eradication rates dropping from 90% to 20% with resistant strains 1, 2
- Avoid repeating any antibiotics that failed previously, especially clarithromycin and levofloxacin 1, 2
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 2
Rifabutin-Based Triple Therapy
Rifabutin triple therapy is highly effective as rescue therapy after multiple treatment failures. 1, 2
The regimen consists of:
Rifabutin 150 mg twice daily 1
PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) for 14 days 1
Rifabutin resistance is extremely rare, making this an effective rescue option 1
Reserve for third or fourth-line therapy after multiple failures 1, 2
High-Dose Dual Amoxicillin-PPI Therapy
This is an alternative rescue therapy when other options have been exhausted. 1
The regimen consists of:
- Amoxicillin 2-3 grams daily in 3-4 split doses 1
- High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily for 14 days 1
Special Populations
Patients with Penicillin/Amoxicillin Allergy
Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1, 2
- 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
Patients with Clarithromycin Allergy or Prior Macrolide Exposure
Use bismuth quadruple therapy as first-line treatment. 1, 2
- Avoid clarithromycin if the patient has prior macrolide exposure for any indication—cross-resistance is universal within the macrolide family 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
Critical Testing Pitfalls
- Never use serology to confirm eradication—antibodies may persist long after successful treatment 1
- Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 2
Adjunctive Therapies
Probiotics can be used as adjunctive treatment to reduce antibiotic-associated diarrhea and improve patient compliance, but have no solid evidence to increase eradication rates. 1, 2
- Diarrhea occurs in 21-41% of patients during the first week of H. pylori eradication therapy 1
- Probiotics should not be considered as primary treatment and are of unproven benefit for improving eradication rates 1, 2
Common Pitfalls to Avoid
- Standard-dose PPI once daily is inadequate—always use twice-daily dosing to maximize gastric pH elevation 1, 2
- Avoid concomitant use of other antacids (e.g., H2-receptor antagonists) with PPIs during treatment 1, 2
- Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1
- Complete adherence to the full treatment course is essential for successful eradication 3
- Patient factors such as smoking and high BMI can affect treatment success—smoking increases the risk of eradication failure (OR 1.95), and high BMI leads to lower drug concentrations at the gastric mucosal level 1
FDA-Approved Regimens for H. pylori
The FDA approves amoxicillin for H. pylori treatment in two regimens: 4
Triple Therapy
- Amoxicillin 1 gram twice daily (every 12 hours) 4
- Clarithromycin 500 mg twice daily 4
- Lansoprazole 30 mg twice daily for 14 days 4
Dual Therapy
- Amoxicillin 1 gram three times daily (every 8 hours) 4
- Lansoprazole 30 mg three times daily for 14 days 4
However, these FDA-approved regimens are now considered suboptimal due to rising clarithromycin resistance, and bismuth quadruple therapy is preferred in current clinical practice. 1, 2