What is the recommended first‑line regimen for eradicating Helicobacter pylori in an otherwise healthy adult?

Helicobacter pylori First-Line Treatment

Bismuth quadruple therapy for 14 days is the definitive first-line regimen for H. pylori eradication in otherwise healthy adults, consisting of high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

Recommended First-Line Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even in regions with high clarithromycin and metronidazole resistance (>15-20%), making it the most reliable empiric choice in North America and most of Europe. 1, 2

Specific Dosing Protocol

• High-dose PPI twice daily – esomeprazole or rabeprazole 40 mg BID is strongly preferred over other PPIs because it increases cure rates by 8-12% 1, 2
• Bismuth subsalicylate 262 mg (two tablets) four times daily 1
• Metronidazole 500 mg three to four times daily 1, 2
• Tetracycline 500 mg four times daily 1, 2
• Duration: 14 days mandatory – extending from 7 to 14 days improves eradication by approximately 5% 3, 1, 2

Administration Details

• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1
• Bismuth should be taken 30 minutes before meals and at bedtime 1
• Metronidazole should be taken 30 minutes after meals 1

Why Bismuth Quadruple Therapy Is Preferred

• Clarithromycin resistance now exceeds 15-20% in most of North America and Central, Western, and Southern Europe, making traditional triple therapy achieve only 70% eradication rates 3, 1, 2
• Bismuth has no described bacterial resistance, and its synergistic effect overcomes metronidazole resistance in vitro 3, 1
• 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 1

Alternative First-Line Option (Restricted Use)

Concomitant non-bismuth quadruple therapy may be used only when bismuth is unavailable AND regional clarithromycin resistance is documented to be <15%: 1, 2

• Esomeprazole or rabeprazole 40 mg BID
• Amoxicillin 1000 mg BID
• Clarithromycin 500 mg BID
• Metronidazole 500 mg BID
• Duration: 14 days

Do not use standard triple therapy (PPI + clarithromycin + amoxicillin) empirically in North America or Europe, where clarithromycin resistance exceeds 15-20% and eradication rates fall to approximately 70%. 3, 1, 2

Critical Optimization Factors

• Never use standard-dose PPI once daily – this is a major cause of treatment failure; twice-daily high-dose PPI is mandatory 1, 2, 4
• Avoid pantoprazole – 40 mg pantoprazole provides acid suppression equivalent to only 9 mg omeprazole 1
• Never shorten therapy below 14 days – this reduces eradication success by approximately 5% 3, 1, 2, 5
• Complete the full 14-day course to maximize eradication rates and prevent antibiotic resistance 1, 2

Confirmation of Eradication (Test-of-Cure)

• Perform urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy 3, 1, 2, 4
• Discontinue PPI at least 2 weeks (preferably 7-14 days) before testing to avoid false-negative results 3, 1, 2
• Never use serology for test-of-cure – antibodies persist long after successful eradication 3, 1, 2

Second-Line Options After First-Line Failure

If bismuth quadruple therapy fails, levofloxacin triple therapy is recommended (provided no prior fluoroquinolone exposure): 3, 1, 2, 4

• Esomeprazole or rabeprazole 40 mg BID
• Amoxicillin 1000 mg BID
• Levofloxacin 500 mg once daily
• Duration: 14 days

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 3, 1, 2, 4

Special Populations

In patients with confirmed penicillin allergy, bismuth quadruple therapy is the first-choice regimen because it contains tetracycline rather than amoxicillin. 1, 2 Consider formal allergy testing after first-line failure, as most reported allergies are not true allergies. 1

Common Pitfalls to Avoid

• Never repeat clarithromycin if it was in a failed regimen – resistance develops rapidly after exposure, dropping eradication rates from 90% to 20% with resistant strains 1, 2
• Do not assume low clarithromycin resistance without local surveillance data – most regions now have high resistance rates 1
• Avoid concomitant, sequential, or hybrid therapies – they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1
• Do not use levofloxacin as first-line therapy – this accelerates resistance development and eliminates a valuable rescue option 1