What is the preferred first‑line regimen for Helicobacter pylori eradication in an adult with no drug allergies, no prior H. pylori treatment, and no medication contraindications?

First-Line H. pylori Eradication Regimen

Bismuth quadruple therapy for 14 days is the definitive first-line treatment for H. pylori eradication in an adult with no drug allergies, no prior treatment, and no contraindications. 1, 2, 3

Recommended Regimen Components

The preferred regimen consists of:

• Esomeprazole or rabeprazole 40 mg twice daily (strongly preferred over other PPIs; increases cure rates by 8-12%) 1, 2, 3
• Bismuth subsalicylate 262 mg (two tablets) 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
• Duration: 14 days mandatory (improves eradication by ~5% compared to shorter courses) 1, 2, 3, 4

Critical Administration Instructions

• PPI: Take 30 minutes before meals on an empty stomach; avoid concomitant antacids 1, 2
• Bismuth: Take 30 minutes before meals and at bedtime 1, 2
• Metronidazole: Take 30 minutes after meals 1, 2
• High-dose PPI twice daily is mandatory—once-daily dosing is a major cause of treatment failure 1, 2, 3

Why Bismuth Quadruple Therapy Is First-Line

Clarithromycin resistance now exceeds 15-20% across North America and most of Europe, reducing traditional triple therapy success to only ~70% 1, 2, 3. In contrast:

• Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance 1, 2, 3
• No bacterial resistance to bismuth has been documented 1, 3
• Tetracycline resistance remains rare (<5%) 1, 2
• Bismuth's synergistic effect overcomes metronidazole resistance in vitro 1, 3
• Uses WHO "Access" antibiotics (tetracycline, metronidazole) rather than "Watch" agents (clarithromycin, levofloxacin), supporting antimicrobial stewardship 1, 2

Alternative First-Line Option (Only If Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days may be used only if bismuth is unavailable and local clarithromycin resistance is documented <15% 1, 3:

• Esomeprazole or rabeprazole 40 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1

This option should be avoided in most clinical settings because clarithromycin resistance exceeds 15% in the majority of North America and Europe 1, 2, 3.

Expected Side Effects

• Diarrhea occurs in 21-41% of patients during the first week due to gut microbiota disruption; this does not indicate treatment failure 1
• Consider adjunctive probiotics to reduce diarrhea risk and improve compliance 1, 3

Confirmation of Eradication

• Perform urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy 1, 2, 3
• Discontinue PPI at least 2 weeks before testing 1, 2, 3
• Never use serology for test-of-cure—antibodies persist long after successful eradication 1, 3

Critical Pitfalls to Avoid

• Never use once-daily PPI dosing—it is a major cause of treatment failure 1, 2
• Avoid pantoprazole 40 mg—its acid-suppression effect equals only ~9 mg omeprazole, yielding inferior outcomes 1
• Do not shorten therapy below 14 days—this reduces eradication by ~5% 1, 2, 3, 4
• Do not use clarithromycin-based triple therapy empirically unless local surveillance confirms resistance <15%, which is rare 1, 2, 3

Patient Factors That Reduce Success

• Smoking roughly doubles the odds of treatment failure (OR ~1.95)—advise cessation during therapy 1, 2
• Elevated BMI/obesity may lower gastric mucosal drug concentrations, potentially reducing efficacy 1, 2
• Poor compliance is a leading cause of failure—provide clear written instructions and emphasize completing the full 14-day course 1, 2