What is the standard first‑line therapy for a 33‑year‑old woman with confirmed Helicobacter pylori infection (positive urea breath test) and no drug allergies or comorbidities?

Standard First-Line Treatment for H. pylori Infection

Bismuth quadruple therapy for 14 days is the definitive first-line treatment for this 33-year-old woman with confirmed H. pylori infection. 1, 2, 3

Recommended Regimen Components

The standard bismuth quadruple therapy consists of:

• High-dose PPI twice daily – esomeprazole or rabeprazole 40 mg twice daily is strongly preferred over standard PPIs, as it increases cure rates by 8-12% 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 – this improves eradication by approximately 5% compared to shorter regimens 1, 2, 4, 3

Why This Regimen Is Preferred

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it superior to traditional triple therapy in North America where clarithromycin resistance now exceeds 15-20% in most regions. 1, 2, 5

Key advantages include:

• No bacterial resistance to bismuth has been described 1, 5
• Tetracycline resistance remains rare (<5%) 1, 2
• Bismuth's synergistic effect overcomes metronidazole resistance in vitro, maintaining efficacy even against resistant strains 1, 2, 5

Critical Optimization Factors

PPI administration is crucial: Take 30 minutes before meals on an empty stomach, without concomitant antacids, to maximize absorption and acid suppression. 1

The 14-day duration is non-negotiable – extending from 7 to 14 days consistently yields approximately 5% higher eradication success across all regimens. 1, 2, 4, 3

Alternative First-Line Option (If Bismuth Unavailable)

If bismuth is not accessible, concomitant non-bismuth quadruple therapy for 14 days is the alternative: 1, 2

• High-dose PPI twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This alternative should only be used in areas with documented clarithromycin resistance <15%, which is increasingly rare in North America. 1, 2

Confirmation of Eradication (Test-of-Cure)

Test-of-cure is mandatory for all patients using urea breath test or validated monoclonal stool antigen test at least 4 weeks after completing therapy. 2, 5, 3

Discontinue PPIs at least 2 weeks before testing to avoid false-negative results. 2, 5

Never use serology for test-of-cure – antibodies persist long after successful eradication. 1

Common Pitfalls to Avoid

• Do not use standard-dose PPI once daily – this is a major cause of treatment failure 1
• Do not shorten therapy below 14 days – this reduces eradication success 1, 2, 4
• Do not use clarithromycin-based triple therapy empirically – clarithromycin resistance exceeds 15% in most North American regions, making this regimen unacceptably ineffective 1, 6
• Avoid pantoprazole – its acid-suppression potency is markedly lower (40 mg pantoprazole ≈ 9 mg omeprazole equivalent) 1

Expected Side Effects and Counseling

Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota; this does not indicate treatment failure. 1

Consider adjunctive probiotics to reduce diarrhea risk and improve compliance, though they do not significantly increase eradication rates. 1

Counsel the patient on the importance of completing the full 14-day course despite side effects, as poor compliance accounts for >10% of treatment failures. 2