What is the recommended treatment for H pylori (Helicobacter pylori) infection?

H. pylori Treatment

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to the synergistic effect of bismuth with other antibiotics, and bacterial resistance to bismuth remains extremely rare. 1, 2, 3

The specific regimen consists of: 1, 2

• High-dose PPI (e.g., omeprazole 40 mg, esomeprazole 40 mg, or rabeprazole 40 mg) twice daily
• Bismuth subsalicylate 525 mg four times daily
• Metronidazole 500 mg three to four times daily
• Tetracycline HCl 500 mg four times daily
• Duration: 14 days (not 7 or 10 days)

Why Bismuth Quadruple Therapy is Preferred

Traditional clarithromycin-based triple therapy should be abandoned because clarithromycin resistance now exceeds 15-20% in most regions of North America and Europe, reducing eradication rates to approximately 70% or lower—well below the 80% minimum target. 2, 3 When H. pylori strains are clarithromycin-resistant, eradication rates drop to approximately 20% compared to 90% with susceptible strains. 3

The World Health Organization has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotic development due to high clarithromycin resistance rates. 3

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available, consisting of: 2, 3

• PPI twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing the development of resistance during treatment. 3

Critical Optimization Strategies

PPI Dosing

Always use high-dose PPI twice daily—standard-dose PPI once daily is inadequate. 4, 1, 2 High-dose PPI increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity. 1, 2 Specific high-dose options include esomeprazole or rabeprazole 40 mg twice daily. 4

Treatment Duration

The 14-day duration is mandatory—extending from 7 to 14 days improves eradication success by approximately 5%. 4, 1, 2

Medication Timing

Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 5

Second-Line Treatment After First-Line Failure

After failure of first-line therapy, choose between: 4, 1

1. Bismuth quadruple therapy for 14 days (if not previously used) 4, 1
2. Levofloxacin triple therapy for 14 days, consisting of:
   • PPI twice daily
   • Amoxicillin 1000 mg twice daily
   • Levofloxacin 500 mg once daily (or 250 mg twice daily)

However, rising rates of levofloxacin resistance must be taken into account—do not use levofloxacin empirically if the patient has had prior fluoroquinolone exposure for any indication. 4, 1, 2

Third-Line and Rescue Therapy

After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 2

When susceptibility testing is unavailable: 1, 3

• Use antibiotics not previously used or for which resistance is unlikely (amoxicillin, tetracycline, bismuth, or furazolidone)
• Rifabutin triple therapy for 14 days is highly effective as rescue therapy: rifabutin 150 mg twice daily, amoxicillin 1000 mg twice daily, and PPI twice daily 1, 3
• Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections 1

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2 Serology should never be used to confirm eradication as antibodies may persist long after successful treatment. 1, 2

Critical Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 3
• Never repeat clarithromycin if the patient has prior macrolide exposure for any indication, as cross-resistance is universal within the macrolide family 3
• Never use standard-dose PPI once daily—always use twice-daily dosing to maximize gastric pH elevation 4, 1, 2
• Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin 1, 2, 3
• In patients with penicillin allergy, amoxicillin can be replaced with tetracycline in bismuth quadruple therapy, but consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 2, 3
• Fluoroquinolones (like levofloxacin) should be used as a last choice due to risk of serious side effects and rapidly rising resistance rates 3

Special Populations

In patients with severe renal impairment (GFR <30 mL/min), amoxicillin dosing must be adjusted: 5

• GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours
• GFR <10 mL/min: 500 mg or 250 mg every 24 hours
• Hemodialysis: 500 mg or 250 mg every 24 hours, with an additional dose during and at the end of dialysis

In children, fluoroquinolones and tetracyclines should not be used, limiting treatment options. 2