What is bismuth quadruple therapy for Helicobacter pylori (H. pylori)?

Bismuth Quadruple Therapy for H. pylori

Bismuth quadruple therapy is recommended as the first-line treatment for H. pylori infection, consisting of a proton pump inhibitor, bismuth, tetracycline, and metronidazole given for 14 days, with an eradication rate of approximately 85%. 1, 2

Components of Bismuth Quadruple Therapy

Bismuth quadruple therapy typically includes:

• Proton pump inhibitor (PPI) twice daily
• Bismuth subcitrate/subsalicylate (120-240mg) four times daily
• Tetracycline (500mg) four times daily
• Metronidazole (500mg) three to four times daily

This combination is typically administered for 14 days, though 10-day regimens have shown similar efficacy in recent studies 3, 4.

Rationale for Bismuth Quadruple Therapy

Bismuth quadruple therapy has become the preferred first-line treatment for several important reasons:

• Overcomes antibiotic resistance: Effective even in areas with high clarithromycin and metronidazole resistance 1
• High eradication rates: Achieves approximately 85% eradication rate 2
• Antibiotic stewardship: Avoids overuse of clarithromycin, which is important for antimicrobial stewardship 1

Duration of Therapy

While 14-day therapy has traditionally been recommended:

• The 2019 Gastroenterology guidelines recommend 14-day bismuth quadruple therapy when susceptibility testing or regional data are not available 1
• Recent high-quality studies show that 10-day regimens may be non-inferior to 14-day regimens:
  • A 2024 randomized clinical trial demonstrated non-inferior eradication rates with 10-day vs. 14-day therapy (92.4% vs. 92.9% by intention-to-treat analysis) 4
  • The 10-day regimen showed fewer adverse effects, particularly dizziness and vomiting 4

Alternative Formulations

A simplified three-in-one pill formulation (Pylera) containing bismuth subcitrate potassium, metronidazole, and tetracycline has shown excellent efficacy:

• In a real-life study, this formulation achieved 90.8% eradication rate by intention-to-treat analysis when given with a PPI for 10 days 5
• This formulation may improve adherence and simplify the regimen

Monitoring and Follow-up

After completion of bismuth quadruple therapy:

• Confirmation of eradication should be performed at least 4 weeks after completion of treatment
• Urea breath test or monoclonal stool antigen test are the preferred non-invasive tests for confirmation 2

Common Side Effects

Patients should be informed about potential side effects:

• Darkening of stool (from bismuth)
• Metallic taste
• Nausea
• Diarrhea
• Dizziness and vomiting (more common with 14-day regimens) 4

Key Considerations

• Bismuth quadruple therapy is particularly valuable in regions with high clarithromycin resistance
• Patient compliance is crucial for successful eradication
• The regimen should be taken with meals to improve tolerance and efficacy
• If bismuth is not available, concomitant non-bismuth quadruple therapy is an acceptable alternative 1, 2

In conclusion, bismuth quadruple therapy represents the current standard of care for first-line H. pylori eradication, with strong evidence supporting its efficacy even in areas with high antibiotic resistance.