Components of Quadruple Therapy for H. pylori
Bismuth quadruple therapy consists of four medications taken together: a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate or bismuth subcitrate, metronidazole, and tetracycline, administered for 10-14 days (with 14 days preferred). 1, 2, 3
Specific Medication Components and Dosing
The standard bismuth quadruple regimen includes:
- PPI (e.g., omeprazole 20 mg or equivalent): Twice daily, taken 30 minutes before meals 1, 2
- Bismuth subsalicylate 262 mg OR bismuth subcitrate 120 mg: Four times daily 2, 3
- Metronidazole 500 mg: Three to four times daily (total daily dose 1.5-2 g) 1, 2
- Tetracycline 500 mg: Four times daily 1, 2, 3
A convenient formulation (Pylera®) combines bismuth subcitrate, metronidazole, and tetracycline in a single capsule, dosed as 3 capsules four times daily with a PPI twice daily. 4, 5
Alternative Non-Bismuth Quadruple Therapy
When bismuth is unavailable, concomitant non-bismuth quadruple therapy is the recommended alternative, consisting of: 1, 2, 3
- PPI: Twice daily 1, 2
- Amoxicillin 1000 mg: Twice daily 1, 2
- Clarithromycin 500 mg: Twice daily 1, 2
- Metronidazole 500 mg: Twice daily 1, 2
- Duration: 10-14 days (14 days preferred) 1, 2
This regimen achieves similar efficacy to bismuth quadruple therapy in areas of high clarithromycin resistance, with eradication rates of 94-98% in intention-to-treat analysis. 4
Treatment Duration Considerations
Fourteen days is superior to shorter durations, improving eradication success by approximately 5% compared to 7-10 day regimens. 1, 3 All three major consensus guidelines (Toronto, Maastricht V/Florence, and American College of Gastroenterology) recommend 14 days for first-line therapies to maximize the probability of success on the first attempt. 1
Why Bismuth Quadruple Therapy is Preferred
- Bacterial resistance to bismuth is extremely rare, making this regimen effective even against metronidazole-resistant strains due to synergistic effects. 2, 3
- Achieves 80-90% eradication rates even with dual resistance to clarithromycin and metronidazole. 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. 2
- Remains highly effective as rescue therapy after multiple treatment failures, with 87% per-protocol eradication rates even in patients with multiresistant strains. 5
Critical Pitfalls to Avoid
- Never use standard once-daily PPI dosing—twice-daily high-dose PPI is mandatory to maximize gastric pH elevation and antibiotic efficacy. 1, 2
- Do not assume 7-10 days is adequate—while some guidelines list 10-14 days as acceptable, 14 days consistently produces superior results. 1
- Avoid repeating antibiotics from failed prior regimens, particularly clarithromycin and levofloxacin, as resistance develops rapidly after exposure. 2, 3
- Higher metronidazole doses (1.5-2 g daily) improve eradication rates even with resistant strains when combined with bismuth. 2
Side Effects and Compliance
Adverse events occur in 46-66% of patients receiving bismuth quadruple therapy, though most are mild and do not require treatment discontinuation. 4, 5 Common side effects include darkening of the tongue and stool (from bismuth), diarrhea, and gastrointestinal upset. 5 The concomitant non-bismuth quadruple regimen has a slightly higher side effect rate (50-57%) compared to bismuth quadruple therapy. 4, 6