What is the recommended first‑line therapy for an adult with confirmed Helicobacter pylori infection who has no drug allergies, no prior Helicobacter pylori treatment, and no severe comorbidities?

Treatment for H. Pylori

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection in adults without drug allergies or prior treatment failures, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1, 2

First-Line Treatment Regimen

The standard bismuth quadruple therapy consists of:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, as they increase cure rates by 8-12% compared to other PPIs) 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 daily) 1, 2
• Tetracycline 500 mg four times daily 1, 2
• Duration: 14 days mandatory (improves eradication by approximately 5% compared to 7-10 day regimens) 1, 3

This regimen is superior because bismuth has no described bacterial resistance, tetracycline resistance remains rare (<5%), and the synergistic effect of bismuth overcomes metronidazole resistance even when present in vitro. 1, 2

Critical Optimization Factors

PPI administration is crucial for success:

• Take PPI 30 minutes before meals on an empty stomach 1, 2
• Never use concomitant antacids (H2-blockers, calcium carbonate) as they interfere with PPI absorption 1
• Twice-daily dosing is mandatory—standard once-daily PPI is inadequate and significantly reduces efficacy 1

Complete the full 14-day course without interruption. 1, 3 The Toronto Consensus, Maastricht V/Florence, and American College of Gastroenterology all endorse 14 days as the evidence-based duration. 3

Alternative First-Line Option (Restricted Use)

Concomitant non-bismuth quadruple therapy may be considered ONLY in areas with documented clarithromycin resistance below 15%:

• PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days 1, 3

However, clarithromycin resistance now exceeds 15-20% in most of North America and Central, Western, and Southern Europe, making this option inappropriate in most regions. 1 Do not use clarithromycin-based therapy empirically without local resistance data showing <15% resistance. 1

Why Bismuth Quadruple Therapy Is Preferred

The American Gastroenterological Association explicitly recommends avoiding concomitant, sequential, or hybrid therapies as they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit. 1 Bismuth quadruple therapy 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

Common Pitfalls to Avoid

• Never shorten treatment below 14 days—this is the single most common error that reduces eradication rates 1, 3
• Do not substitute doxycycline for tetracycline—it yields significantly inferior eradication rates 1
• Avoid pantoprazole 40 mg—its acid-suppression potency is markedly lower (equivalent to only 9 mg omeprazole) 1
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using:

• Urea breath test (preferred), OR 1, 2
• Validated monoclonal stool antigen test 1, 2

Critical testing requirements:

• Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 2
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1

Patient Counseling Points

Warn patients about expected side effects:

• Diarrhea occurs in 21-41% during the first week due to disruption of gut microbiota 1
• Bismuth causes black stools and black tongue (benign, temporary) 1
• Metronidazole requires absolute alcohol avoidance during treatment and for 48 hours after completion (disulfiram-like reaction) 1

Emphasize strict adherence: More than 10% of patients are poor compliers, leading to much lower eradication rates and development of antibiotic resistance. 1

Special Populations

For patients with penicillin allergy: Bismuth quadruple therapy is the first choice because it contains tetracycline, not amoxicillin. 1, 2 However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use in future regimens if needed. 1