What is the recommended first‑line eradication regimen for an adult with uncomplicated Helicobacter pylori infection who has no known drug allergies, no prior H. pylori treatment, and no contraindications to the standard therapies?

Recommended First-Line H. pylori Eradication Regimen

Bismuth quadruple therapy for 14 days is the definitive first-line treatment for H. pylori infection in adults without contraindications, achieving 80-90% eradication rates even in regions with high clarithromycin resistance. 1, 2, 3

Specific Regimen Components

The standard bismuth quadruple regimen consists of:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals on an empty stomach) 1, 2, 3
• Bismuth subsalicylate 262 mg (two tablets) four times daily or bismuth subcitrate 120 mg four times daily, taken 30 minutes before meals and at bedtime 3
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily), taken 30 minutes after meals 3
• Tetracycline 500 mg four times daily 1, 2, 3

Treatment duration must be 14 days—this is mandatory, as extending from 7 to 14 days improves eradication success by approximately 5%. 1, 2, 3

Why Bismuth Quadruple Therapy Is Preferred

This regimen is recommended as first-line because:

• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates 1, 3
• Bismuth quadruple therapy is not affected by clarithromycin resistance and achieves 80-90% eradication even with dual resistance to clarithromycin and metronidazole 1, 2, 3
• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare 1, 3
• Bismuth's synergistic effect overcomes metronidazole resistance in vitro 1, 3
• The regimen uses antibiotics from the WHO "Access group" (tetracycline, metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 3

Alternative First-Line Option (Only in Low-Resistance Areas)

If local clarithromycin resistance is documented to be <15%, concomitant non-bismuth quadruple therapy for 14 days may be considered:

• High-dose PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily 1, 2, 3

However, most regions now have clarithromycin resistance >15%, making this option rarely appropriate without local surveillance data. 3

Critical Optimization Factors

To maximize eradication success:

• Use esomeprazole or rabeprazole 40 mg twice daily rather than standard-dose PPIs—this increases cure rates by 8-12% compared to other PPIs 1, 2, 3
• Never use pantoprazole 40 mg, as its potency is markedly lower (equivalent to only 9 mg omeprazole) 3
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1, 3
• Complete the full 14-day course—shorter durations significantly reduce eradication rates 1, 2, 3
• Do not substitute doxycycline for tetracycline—doxycycline yields significantly inferior eradication rates 3

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test:

• 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 persist long after successful treatment 1, 2

Common Pitfalls to Avoid

• Do not use standard triple therapy (PPI + clarithromycin + amoxicillin) empirically—clarithromycin resistance makes this regimen achieve <80% eradication in most regions 1, 3
• Do not use standard-dose PPI once daily—this is inadequate and significantly reduces treatment efficacy 1, 2
• Do not shorten treatment duration below 14 days 1, 2, 3
• Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 3

Patient Counseling Points

• Smoking increases risk of eradication failure (odds ratio 1.95) 3
• High BMI increases risk of failure due to lower drug concentrations at the gastric mucosal level 3
• Diarrhea occurs in 21-41% of patients during the first week due to disruption of gut microbiota 3
• Consider adjunctive probiotics to reduce diarrhea and improve compliance, though evidence for increased eradication rates is limited 1, 2, 3
• Compliance is crucial—more than 10% of patients are poor compliers, leading to much lower eradication rates 3