What are the current guideline‑recommended drugs, doses, and duration for bismuth‑based quadruple therapy to eradicate Helicobacter pylori in adults (≥ 18 years), including treatment‑naïve and most treatment‑experienced patients?

Current Guidelines for Bismuth Quadruple Therapy for H. pylori

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori eradication, consisting of a PPI twice daily, bismuth subsalicylate (262 mg) or bismuth subcitrate (120 mg) four times daily, metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily. 1

Complete Regimen Components and Dosing

Proton Pump Inhibitor (PPI)

• High-dose PPI twice daily is mandatory 1
• Standard doses: esomeprazole 20 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, or rabeprazole 20 mg 1
• Esomeprazole or rabeprazole 40 mg twice daily is strongly preferred, as these increase cure rates by 8-12% compared to standard PPIs 1, 2
• Take 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2

Bismuth Component

• Bismuth subsalicylate 262 mg: 2 tablets four times daily 1
• OR bismuth subcitrate 120 mg: 1 tablet four times daily 1
• Take 30 minutes before meals and at bedtime 1

Antibiotics

• Tetracycline 500 mg four times daily 1
• Metronidazole 500 mg three to four times daily (or 400 mg four times daily) 1
• Take 30 minutes after meals 1

Treatment Duration

14 days is the recommended duration 1

• Toronto Consensus and Maastricht V/Florence recommend 14 days 1
• ACG lists 10-14 days as acceptable, but 14 days is superior 1
• 14-day duration improves eradication by approximately 5% compared to 7-10 day regimens 1

Efficacy and Rationale

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high dual resistance to clarithromycin and metronidazole 1, 2

• No bacterial resistance to bismuth has been described 2, 3
• Tetracycline resistance remains rare (<5%) 2, 3
• Bismuth's synergistic effect overcomes metronidazole resistance in vitro, making the regimen effective even against resistant strains 1, 2, 3
• Particularly recommended in areas with clarithromycin resistance >15% 1, 2

Alternative When Bismuth Unavailable

Concomitant non-bismuth quadruple therapy for 14 days 1, 2:

• PPI twice daily
• Amoxicillin 1000 mg twice daily
• Metronidazole 500 mg twice daily
• Clarithromycin 500 mg twice daily
• Only use in areas with clarithromycin resistance <15% 2, 3

Critical Optimization Factors

• Complete the full 14-day course to maximize eradication rates 1
• Do NOT substitute doxycycline for tetracycline, as results are significantly inferior 1
• Avoid pantoprazole due to significantly lower potency (40 mg pantoprazole = 9 mg omeprazole equivalents) 1
• Higher doses of metronidazole (1.5-2 g daily in divided doses) improve eradication rates even with resistant strains when combined with bismuth 2

Special Populations

For patients with penicillin allergy, bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1, 2, 3

Common Pitfalls to Avoid

• Never use standard-dose PPI once daily—always use twice-daily dosing 2, 3
• Do not shorten treatment duration below 14 days 1
• Avoid concomitant use of other antacids such as H2-receptor antagonists 2
• After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment 2, 3, 4

Confirmation of Eradication

Test for eradication success at least 4 weeks after completion of therapy using urea breath test or validated monoclonal stool antigen test 2, 3

• Discontinue PPI at least 2 weeks before testing 2, 3
• Never use serology to confirm eradication—antibodies persist long after successful treatment 2