What is the recommended first‑line therapy for eradication of Helicobacter pylori in an adult patient without known drug allergies or contraindications?

First-Line Treatment for H. pylori Infection

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori eradication in adults without known drug allergies or contraindications, achieving 80–90% eradication rates even in regions with high clarithromycin and metronidazole resistance. 1, 2

Recommended First-Line Regimen: Bismuth Quadruple Therapy

The optimal regimen consists of four components taken for 14 days 1, 3, 2:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred; alternatives include omeprazole 20 mg, lansoprazole 30 mg, or pantoprazole 40 mg—though pantoprazole should be avoided due to inferior acid suppression) 1, 2
• Bismuth subsalicylate 262 mg (two tablets) four times daily or bismuth subcitrate 120 mg four times daily 1, 2
• Metronidazole 500 mg three to four times daily (total 1.5–2 g/day) 1, 2
• Tetracycline 500 mg four times daily 1, 2

All medications should be taken for the full 14-day duration—extending treatment from 7 to 14 days improves eradication success by approximately 5% 1, 3, 4. The PPI should be taken 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2.

Why Bismuth Quadruple Therapy Is Preferred

Bismuth quadruple therapy is superior to traditional triple therapy because clarithromycin resistance now exceeds 15–20% in most of North America and Europe, making triple therapy achieve only 70% eradication rates—well below the 80% minimum target 1, 3. In contrast, bismuth quadruple therapy achieves 80–90% eradication even against strains with dual resistance to clarithromycin and metronidazole 1, 2, 4. No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare (<5%) 1, 2.

The regimen also 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 1.

Alternative First-Line Option (Restricted Use)

Concomitant non-bismuth quadruple therapy may be used only in regions with documented clarithromycin resistance <15% 1, 3, 4:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
• Amoxicillin 1000 mg twice daily 1, 4
• Clarithromycin 500 mg twice daily 1, 4
• Metronidazole 500 mg twice daily 1, 4
• Duration: 14 days 1, 4

This regimen should not be used empirically without local resistance data, as most regions now have clarithromycin resistance >15% 1, 3.

Critical Optimization Factors

PPI Dosing

High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate and significantly reduces treatment efficacy 1, 3, 2. Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8–12% compared to other PPIs 1, 2. The PPI should be taken 30 minutes before meals on an empty stomach 1, 2.

Treatment Duration

All regimens must be given for 14 days, not shorter 1, 3, 2, 4. The Toronto Consensus, Maastricht V/Florence, and American College of Gastroenterology all endorse 14 days as the standard of care 1, 4.

Antibiotic Selection

Never use clarithromycin-based triple therapy empirically in areas where clarithromycin resistance exceeds 15%—when H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20% 1, 3.

Common Pitfalls to Avoid

• Never use once-daily PPI dosing—this is a major cause of treatment failure 1, 2
• Do not shorten therapy below 14 days—this reduces eradication success by ~5% 1, 3, 4
• Avoid pantoprazole if higher-potency PPIs are available—40 mg pantoprazole provides acid suppression equivalent to only 9 mg omeprazole 1
• Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1, 3
• Never substitute doxycycline for tetracycline—doxycycline yields significantly inferior eradication rates 1

Special Populations

In patients with penicillin allergy, bismuth quadruple therapy is the first-choice regimen because it contains tetracycline rather than amoxicillin 1, 2. Consider penicillin allergy testing to enable amoxicillin use if bismuth quadruple therapy fails 1, 2.

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using urea breath test or validated monoclonal stool antigen test 1, 3, 2. Discontinue PPI at least 2 weeks before testing 1, 3, 2. Never use serology to confirm eradication—antibodies may persist long after successful treatment 1, 3.