What is the recommended first‑line regimen for Helicobacter pylori eradication in an adult patient with no known drug allergies and no prior treatment?

H. pylori Treatment: First-Line Regimen

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

Recommended First-Line Regimen

The optimal regimen consists of:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred; increases cure rates by 8-12% over standard PPIs) 1, 3
• Bismuth subsalicylate 262 mg (2 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 daily) 1, 2
• Tetracycline 500 mg four times daily 1, 2
• Duration: 14 days mandatory (improves eradication by ~5% vs. shorter courses) 1, 3, 4

Why This Regimen Is Superior

• No bacterial resistance to bismuth has been described, making this regimen effective regardless of clarithromycin or metronidazole resistance patterns 1, 3
• Bismuth's synergistic effect overcomes metronidazole resistance that exists in vitro, preserving efficacy even with resistant strains 1, 2
• Tetracycline resistance remains rare (<5%) in most regions 1, 2
• 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, 3

Critical Optimization Factors

PPI Dosing (Mandatory for Success)

• Take 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2
• Twice-daily dosing is non-negotiable; once-daily dosing significantly reduces efficacy 1, 3
• Esomeprazole or rabeprazole 40 mg twice daily are strongly preferred over other PPIs (pantoprazole should be avoided—40 mg provides only ~9 mg omeprazole equivalent) 1, 3

Timing and Administration

• Bismuth and tetracycline: 30 minutes before meals and at bedtime 1, 2
• Metronidazole: 30 minutes after meals to reduce GI side effects 1

Alternative First-Line Option (Restricted Use)

Concomitant non-bismuth quadruple therapy may be used only when bismuth is unavailable and local clarithromycin resistance is documented <15%: 1, 3, 4

• High-dose PPI twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily
• Duration: 14 days

However, bismuth quadruple therapy remains superior because it avoids clarithromycin entirely and achieves higher eradication rates in real-world practice. 1, 3

Common Pitfalls to Avoid

• Never use standard triple therapy (PPI + clarithromycin + amoxicillin) empirically without documented local clarithromycin resistance <15%; this regimen now fails in >30% of patients in most regions 1, 3, 4
• Never shorten treatment below 14 days; 7-10 day regimens reduce success by ~5% 1, 3, 4
• Never use once-daily PPI dosing; this is a major cause of treatment failure 1, 3
• Do not substitute doxycycline for tetracycline; it yields significantly inferior eradication rates 1

Managing Side Effects

• Diarrhea occurs in 21-41% of patients during the first week due to gut microbiota disruption 1
• Consider adjunctive probiotics to reduce diarrhea risk and improve compliance, though evidence for increasing eradication rates is limited 1, 3, 5
• Provide clear patient education on expected side effects, dosing schedule, and the critical importance of completing the full 14-day course 1, 2

Confirmation of Eradication

• Test at least 4 weeks after completing therapy using urea breath test or monoclonal stool antigen test 1, 3, 4
• Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 3
• Never use serology to confirm eradication; antibodies persist long after successful treatment 1, 3

Special Populations

For patients with penicillin allergy, bismuth quadruple therapy is ideal because it contains tetracycline rather than amoxicillin. 1, 2, 3 Consider penicillin allergy testing to potentially enable amoxicillin-based regimens in the future if needed. 1, 2