H. pylori Treatment: First-Line Regimen
Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1, 2, 3
Specific Regimen Components
The standard bismuth quadruple therapy consists of:
- High-dose PPI: Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs as they increase cure rates by 8-12%), taken 30 minutes before meals on an empty stomach 1, 2
- Bismuth subsalicylate: 262 mg (2 tablets) four times daily 1
- Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1, 2
- Tetracycline: 500 mg four times daily 1, 2
- Duration: 14 days mandatory (improves eradication by approximately 5% compared to 7-10 day regimens) 1, 2, 3
Why Bismuth Quadruple Therapy is Preferred
- Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 1
- Bismuth quadruple therapy is not affected by clarithromycin resistance and achieves 80-90% eradication even with dual resistance to clarithromycin and metronidazole 1, 2
- No bacterial resistance to bismuth has been described, and bismuth's synergistic effect overcomes metronidazole resistance even when in vitro resistance is present 1, 2
- Tetracycline and amoxicillin resistance remains rare (<5%), making these antibiotics reliable choices 1
Alternative First-Line Option (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy for 14 days:
- High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1, 2
- Amoxicillin 1000 mg twice daily 1, 4
- Clarithromycin 500 mg twice daily 1
- Metronidazole 500 mg twice daily 1
This regimen should only be used in areas with documented clarithromycin resistance <15%, as it includes clarithromycin which has high resistance rates globally 1, 2
Critical Optimization Factors
- High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate and significantly reduces treatment efficacy by 6-10% 1, 2, 3
- Take PPI 30 minutes before meals on an empty stomach, without concomitant use of other antacids 1, 3
- 14-day duration cannot be shortened—this is superior to 7-10 day regimens by approximately 5% 1, 2, 3
- Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance develops rapidly after exposure 1, 2
Common Pitfalls to Avoid
- Never use clarithromycin-based triple therapy without knowing local resistance patterns—most regions now have clarithromycin resistance >15%, making this approach unacceptable 1
- Never assume low clarithromycin resistance without local surveillance data—if unavailable, assume high resistance and use bismuth quadruple therapy 1
- Do not use levofloxacin empirically as first-line therapy—this accelerates resistance development and eliminates a valuable rescue option 1, 2
- Avoid concomitant, sequential, or hybrid therapies—these include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1
Verification of Eradication
- Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy 1, 2, 3
- Discontinue PPI at least 2 weeks before testing 1, 2, 3
- Never use serology to confirm eradication—antibodies may persist long after successful treatment 1
Special Populations
- Patients with penicillin allergy: Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1, 3
- Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as most patients who report penicillin allergy are found not to have a true allergy 1