H. pylori Quadruple Therapy
Bismuth quadruple therapy is the preferred first-line treatment for H. pylori infection, consisting of a PPI (twice daily), bismuth subcitrate (120-140 mg 3-4 times daily), metronidazole (500 mg 3-4 times daily), and tetracycline (500 mg 4 times daily) for 14 days. 1, 2
Why Bismuth Quadruple Therapy is Preferred
All major guidelines (American College of Gastroenterology, Toronto Consensus, and Maastricht V/Florence Consensus) recommend bismuth quadruple therapy as first-line treatment, particularly in areas with high dual resistance to clarithromycin and metronidazole. 1
Bismuth quadruple therapy is favored because bacterial resistance to bismuth is extremely rare, and it maintains acceptable success rates even in strains displaying in vitro metronidazole resistance. 1, 3
This regimen avoids clarithromycin, which has seen global resistance rates increase from 9% in 1998 to 17.6% in 2008-2009, making traditional triple therapy increasingly ineffective. 2, 4
Specific Dosing Regimen
The standard bismuth quadruple therapy includes: 3
- PPI (high-dose): Esomeprazole 20 mg or rabeprazole 20 mg twice daily (avoid pantoprazole due to lower potency)
- Bismuth subcitrate: 120-140 mg 3-4 times daily
- Tetracycline hydrochloride: 500 mg 4 times daily
- Metronidazole: 500 mg 3-4 times daily
- Duration: 14 days (not 10 days, despite some guidelines listing 10-14 days as acceptable)
Critical Optimization Factors
High-dose PPI (twice daily) is essential and increases eradication efficacy by 6-10% compared to standard doses by reducing gastric acidity and enhancing antibiotic activity. 2, 4 Take PPIs 30 minutes before eating on an empty stomach without concomitant antacids. 1
The 14-day duration is superior to shorter regimens, improving eradication success by approximately 5% compared to 7-10 day courses. 2, 4 The Toronto Consensus specifically recommends 14 days for all first-line treatments to maximize first-attempt success. 1
Alternative First-Line Option: Concomitant (Non-Bismuth) Quadruple Therapy
If bismuth is unavailable, concomitant therapy is an acceptable alternative, consisting of: 1, 2
- PPI twice daily
- Amoxicillin 1000 mg twice daily
- Metronidazole 500 mg twice daily
- Clarithromycin 500 mg twice daily
- Duration: 14 days
This regimen is appropriate for patients from areas of high clarithromycin resistance where bismuth is not available. 1
When NOT to Use Bismuth Quadruple Therapy
Do not use standard triple therapy (PPI + clarithromycin + amoxicillin) in areas where clarithromycin resistance exceeds 15-20%, as eradication rates become unacceptably low. 2, 4, 3 This restriction applies to most regions globally given current resistance patterns.
Second-Line Treatment After Quadruple Therapy Failure
If bismuth quadruple therapy fails, use levofloxacin-based triple therapy: 1, 2, 4
- PPI twice daily
- Amoxicillin 1000 mg twice daily
- Levofloxacin 500 mg once daily (or 250 mg twice daily)
- Duration: 14 days
After two failed eradication attempts with confirmed patient adherence, obtain H. pylori susceptibility testing to guide subsequent regimens. 1, 2
Common Pitfalls to Avoid
Never use doxycycline instead of tetracycline in bismuth quadruple therapy, as multiple studies demonstrate significantly inferior results. 3
Do not repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as this maximizes treatment failure risk. 2
Inadequate PPI dosing is a major cause of treatment failure—always prescribe high-dose (twice daily) PPI, not standard once-daily dosing. 2, 4
Bismuth quadruple therapy is one of the least tolerable H. pylori regimens due to side effects, so counsel patients about potential gastrointestinal symptoms and the importance of adherence despite discomfort. 3
Special Populations
In patients with true penicillin allergy, amoxicillin can be replaced with tetracycline in alternative regimens, or use the standard bismuth quadruple therapy which does not contain penicillin. 1, 3
In children, avoid both fluoroquinolones and tetracyclines, which considerably limits treatment options. 2, 3
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after discontinuing PPIs. 2, 4 Never use serology to confirm eradication, as antibodies persist long after successful treatment. 2, 4