Bismuth-Based Quadruple Therapy for H. pylori Eradication
Bismuth-based quadruple therapy consists of a high-dose proton pump inhibitor (PPI) twice daily, bismuth subcitrate 120–140 mg (or bismuth subsalicylate 262 mg) four times daily, metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily, all given for 14 days. 1, 2
Core Components and Dosing
The four essential medications are:
PPI: Esomeprazole or rabeprazole 40 mg twice daily is strongly preferred because it increases cure rates by 8–12% compared to standard-dose PPIs 1, 2. Standard alternatives include omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 20 mg twice daily, but avoid pantoprazole due to inferior acid suppression 1, 2.
Bismuth: Either bismuth subcitrate 120–140 mg four times daily or bismuth subsalicylate 262 mg (two tablets) four times daily 1, 2, 3. No bacterial resistance to bismuth has been documented 1, 4.
Metronidazole: 500 mg three to four times daily (total 1.5–2 g daily) 1, 2. Bismuth's synergistic effect overcomes metronidazole resistance even when present in vitro 1, 4.
Tetracycline: 500 mg four times daily 1, 2, 3. Tetracycline resistance remains rare at 1–5% globally 1, 4. Never substitute doxycycline, which yields significantly inferior eradication rates 1.
Treatment Duration and Timing
The mandatory duration is 14 days, which improves eradication by approximately 5% compared to 7–10 day regimens 1, 2, 4. While some evidence suggests 10-day therapy may achieve similar results in specific populations 5, the 14-day standard is endorsed by the American Gastroenterological Association, Toronto Consensus, and Maastricht V/Florence guidelines 1, 2.
Timing instructions:
- Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2
- Take bismuth 30 minutes before meals and at bedtime 2
- Take metronidazole 30 minutes after meals 2
Efficacy and Resistance Profile
This regimen achieves 80–90% eradication rates even in areas with high dual resistance to clarithromycin and metronidazole 1, 2, 4. In rescue therapy after failed clarithromycin-based treatment, eradication rates of 93–97% have been documented 6, 7.
The regimen is particularly effective because:
- Bismuth has no documented resistance 1, 4
- Tetracycline resistance remains rare (1–5%) 1, 4
- Bismuth overcomes metronidazole resistance through synergistic effects 1, 4
- The regimen is not affected by clarithromycin resistance 2
Special Populations
For patients with penicillin allergy, bismuth quadruple therapy is the first-choice regimen because it contains tetracycline rather than amoxicillin 1, 2, 4.
In elderly patients (age 73, as in your case):
- Tetracycline is not contraindicated by age alone 2
- The four-times-daily dosing may be challenging; provide clear education on the regimen rationale and importance of completing the full course 2
- Consider shared decision-making if multiple prior failures have occurred 2
Common Pitfalls to Avoid
- Never shorten therapy below 14 days 1, 2, 4
- Never use standard once-daily PPI dosing; twice-daily high-dose PPI is mandatory 1, 2
- Never substitute doxycycline for tetracycline 1
- Never use pantoprazole due to its markedly lower potency (40 mg pantoprazole ≈ 9 mg omeprazole equivalent) 1, 2
- Never repeat clarithromycin if it was in a failed prior regimen, as resistance develops rapidly 2
Verification of Eradication
Test for eradication at least 4 weeks after completing therapy using urea breath test or monoclonal stool antigen test 1, 4. Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 4. Never use serology to confirm eradication, as antibodies persist long after successful treatment 2.
Alternative When Bismuth Is Unavailable
If bismuth is not available, concomitant non-bismuth quadruple therapy (PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days) may be used only in regions where clarithromycin resistance is documented below 15% 1, 2.