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

Treatment for H. pylori Infection

Bismuth quadruple therapy for 14 days is the first-line treatment for H. pylori infection, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1, 2, 3

First-Line Treatment: Bismuth Quadruple Therapy

The optimal regimen consists of: 1, 2, 3

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals)
• Bismuth subsalicylate 262 mg (2 tablets) four times daily
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily)
• Tetracycline 500 mg four times daily
• Duration: 14 days mandatory (improves eradication by ~5% compared to shorter courses)

This regimen is preferred because bacterial resistance to bismuth is extremely rare, and bismuth's synergistic effect overcomes metronidazole resistance even when present. 1, 2, 3 Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy unacceptably ineffective with only 70% eradication rates. 1

Alternative First-Line Option (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days: 1, 2

• High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This regimen administers all antibiotics simultaneously, preventing resistance development during treatment. 1

Critical Optimization Factors

High-dose PPI dosing is mandatory—esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to standard PPIs or dosing. 1, 3 Standard once-daily PPI dosing is inadequate and significantly reduces treatment efficacy. 1

Never use 7-10 day regimens—14 days is the evidence-based duration that maximizes eradication rates. 1, 2, 3

Second-Line Treatment After First-Line Failure

If bismuth quadruple therapy fails, use levofloxacin triple therapy for 14 days (provided no prior fluoroquinolone exposure): 1, 2, 3

• High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily
• Amoxicillin 1000 mg twice daily
• Levofloxacin 500 mg once daily

Critical pitfall: Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1, 2 When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to 20%. 1

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 2, 3

Rifabutin triple therapy for 14 days is a reasonable rescue option: 1, 2

• Rifabutin 150 mg twice daily
• Amoxicillin 1000 mg twice daily
• High-dose PPI twice daily

Rifabutin resistance is extremely rare, making this effective even after multiple treatment failures. 1

High-dose dual therapy (alternative rescue option): 1

• Amoxicillin 2-3 grams daily in 3-4 split doses
• High-dose PPI twice daily
• Duration: 14 days

Special Populations

For patients with penicillin allergy, bismuth quadruple therapy is the first choice since it contains tetracycline, not amoxicillin. 1, 2 However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as most patients who report penicillin allergy are found not to have a true allergy. 1

For patients with tetracycline allergy or unavailability, use amoxicillin-based bismuth quadruple therapy with the same dosing as standard bismuth quadruple therapy but substituting amoxicillin 1000 mg twice daily for tetracycline. 1

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using urea breath test or validated monoclonal stool antigen test. 1, 2, 3 Discontinue PPI at least 2 weeks before testing. 1, 2

Never use serology to confirm eradication—antibodies persist long after successful treatment. 1

Patient Factors Affecting Success

Smoking increases eradication failure risk with an odds ratio of 1.95. 1, 3 High BMI increases failure risk due to lower drug concentrations at the gastric mucosal level. 1, 3 Poor compliance (>10% of patients) leads to much lower eradication rates. 1, 3

Managing Side Effects

Diarrhea occurs in 21-41% of patients during the first week due to gut microbiota disruption. 1 Consider adjunctive probiotics to reduce diarrhea risk and improve compliance, though probiotics have no solid evidence to increase eradication rates. 1, 3

Critical Pitfalls to Avoid

• Never use clarithromycin-based triple therapy empirically without susceptibility testing when regional resistance exceeds 15-20%. 1
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1
• Avoid fluoroquinolones as first-line therapy—this accelerates resistance development and eliminates a valuable rescue option. 1
• Never use standard-dose PPI once daily—always use twice-daily dosing to maximize gastric pH elevation. 1