H. pylori Triple Therapy Regimen
First-Line Treatment: Bismuth Quadruple Therapy is Superior
Bismuth quadruple therapy for 14 days is the preferred first-line treatment, NOT traditional triple therapy, due to global clarithromycin resistance exceeding 15-20% in most regions. 1, 2, 3
Traditional clarithromycin-based triple therapy should be abandoned as first-line treatment in most clinical settings, as clarithromycin resistance has increased from 9% in 1998 to over 17.6% globally, with rates exceeding 20% in North America and most of Europe. 1 When H. pylori strains are clarithromycin-resistant, eradication rates plummet from 90% to approximately 20%. 1
If Triple Therapy Must Be Used (Clarithromycin-Based)
Only use triple therapy in areas with documented clarithromycin resistance below 15%, and only for 14 days. 1, 3
Standard Triple Therapy Regimen:
- PPI: Esomeprazole or rabeprazole 40 mg twice daily (taken 30 minutes before meals on an empty stomach) 4, 1, 2
- Clarithromycin: 500 mg twice daily 4, 5
- Amoxicillin: 1000 mg (1 gram) twice daily 4, 5
- Duration: 14 days (mandatory—not 7 or 10 days) 4, 1, 2, 3
The FDA-approved regimen specifies 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily for 14 days. 5 However, higher-potency PPIs (esomeprazole or rabeprazole 40 mg) increase cure rates by an additional 8-12% compared to standard lansoprazole or omeprazole dosing. 4, 1
Critical Optimization Factors:
- High-dose PPI twice daily is mandatory—standard once-daily dosing reduces efficacy by 6-10%. 1, 2, 3
- Take PPI 30 minutes before meals without concomitant antacids. 1, 2
- 14-day duration improves eradication by approximately 5% compared to 7-10 day regimens. 4, 1, 2, 3
- Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 5
Alternative Triple Therapy (Metronidazole-Based)
If the patient has a penicillin allergy or amoxicillin cannot be used:
- PPI: Esomeprazole or rabeprazole 40 mg twice daily 1
- Clarithromycin: 500 mg twice daily 4
- Metronidazole: 500 mg twice daily 4
- Duration: 14 days 4, 1
Why Bismuth Quadruple Therapy is Preferred
Bismuth quadruple therapy achieves 80-90% eradication rates even against clarithromycin and metronidazole-resistant strains. 1, 2, 3 No bacterial resistance to bismuth has been described, and the synergistic effect of bismuth overcomes metronidazole resistance in vitro. 1, 2
Bismuth Quadruple Therapy Regimen:
- PPI: Esomeprazole or rabeprazole 40 mg twice daily (30 minutes before meals) 1, 2
- Bismuth subsalicylate: 262 mg (2 tablets) four times daily (30 minutes before meals) 4, 2
- Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 4, 1, 2
- Tetracycline: 500 mg four times daily 4, 1, 2
- Duration: 14 days 4, 1, 2, 3
Common Pitfalls to Avoid
- Never use standard-dose PPI once daily—this significantly reduces treatment efficacy. 1, 2, 3
- Never repeat clarithromycin if previously used—resistance develops rapidly after any macrolide exposure. 1, 3
- Never assume low clarithromycin resistance without local surveillance data—most regions now exceed 15-20% resistance. 1
- Never use 7-day regimens—14 days is mandatory for optimal eradication. 4, 1, 2, 3
- Avoid pantoprazole—it has significantly lower potency (40 mg pantoprazole = 9 mg omeprazole equivalents). 4
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2, 3 Never use serology to confirm eradication, as antibodies persist long after successful treatment. 1, 3
Second-Line Treatment After Triple Therapy Failure
If clarithromycin-based triple therapy fails, switch to bismuth quadruple therapy (if not previously used) for 14 days. 1, 2, 3 Never repeat clarithromycin, as eradication rates drop to 20% with resistant strains. 1 After two failed attempts, antibiotic susceptibility testing should guide further treatment. 1, 2, 3