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

Bismuth Quadruple Therapy for H. pylori Infection

Bismuth quadruple therapy is a highly effective first-line treatment for Helicobacter pylori infection consisting of a proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole taken together for 10-14 days, with eradication rates exceeding 90%. 1

Components and Dosing

Bismuth quadruple therapy (PBMT) typically includes:

• PPI: Taken twice daily (e.g., pantoprazole 20mg)
• Bismuth: Bismuth subcitrate 140mg per capsule
• Metronidazole: 125-500mg per dose
• Tetracycline: 125-500mg per dose

The most common formulation is:

• Standard dosing: PPI twice daily + bismuth subcitrate 240mg twice daily + tetracycline 500mg twice daily + metronidazole 500mg twice daily 2
• Single-capsule formulation (Pylera®): Three capsules four times daily (each capsule containing bismuth subcitrate 140mg, metronidazole 125mg, and tetracycline 125mg) plus a PPI twice daily 3

Duration of Therapy

While 14-day therapy was traditionally recommended, recent high-quality evidence shows:

• 10-day regimen is non-inferior to 14-day regimen with similar eradication rates (PP: 97.9% vs 99.3%; ITT: 92.4% vs 92.9%) 4
• 10-day regimen has fewer adverse effects, particularly dizziness (18.5% vs 34.0%) and vomiting (4.5% vs 12.8%) 4
• 10-day regimen is more cost-effective, costing approximately 25% less than the 14-day regimen 2

Efficacy and Advantages

Bismuth quadruple therapy offers several advantages:

• High eradication rates (>90% ITT, >95% PP) even in areas with high antibiotic resistance 1, 3
• Effective against clarithromycin-resistant strains (no resistance develops to bismuth) 1
• Recommended as first-line therapy in areas of high clarithromycin resistance (>15-20%) 1
• Excellent compliance rates (>95%) despite multiple pills 3

Clinical Application

When to Use Bismuth Quadruple Therapy:

1. First-line treatment in areas with high clarithromycin resistance (>15-20%) 1
2. First-line treatment when antibiotic susceptibility testing is unavailable 1
3. Rescue therapy after failure of clarithromycin-based triple therapy 1
4. Alternative for patients with penicillin allergy in high clarithromycin resistance areas 1

Monitoring and Follow-up

• Test for eradication at least 4 weeks after completion of therapy 1
• Use urea breath test (UBT) or monoclonal stool antigen test to confirm eradication 1

Common Pitfalls and Considerations

1. Adverse effects: Generally mild but may include:

   • Darkening of stool (bismuth effect)
   • Metallic taste
   • Nausea/vomiting (more common with 14-day regimen)
   • Dizziness (more common with 14-day regimen)

2. Compliance challenges:

   • High pill burden (especially with separate pills rather than single-capsule formulation)
   • Multiple daily dosing (2-4 times daily)
   • Consider single-capsule formulation (Pylera®) to improve compliance 3

3. Contraindications:

   • Pregnancy (tetracycline contraindicated)
   • Children under 8 years (tetracycline affects bone/teeth development)
   • Severe renal impairment (dose adjustment needed)

4. Drug interactions:

   • Bismuth and tetracycline can chelate with other medications
   • Separate administration from antacids, iron, and certain antibiotics

Evolution of Usage

The use of bismuth quadruple therapy has increased significantly in Europe, from 8.6% of all H. pylori treatments in 2013 to 39% in 2021, reflecting its growing recognition as a highly effective regimen 5. The single-capsule formulation (Pylera®) has become the most frequently used mode of administration (43% of bismuth quadruple therapies) 5.