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

Treatment for H. pylori Infection

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

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it superior to traditional triple therapy. 1 This regimen is recommended because:

• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 1
• Bismuth has no described bacterial resistance, and tetracycline resistance remains rare (<5% globally) 1
• The synergistic effect of bismuth overcomes metronidazole resistance even when strains are resistant in vitro 1

Specific Dosing for Bismuth Quadruple Therapy

• PPI (esomeprazole or rabeprazole preferred): 40 mg twice daily, taken 30 minutes before meals on an empty stomach 1
• Bismuth subsalicylate: 262 mg (2 tablets) four times daily 1
• Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline: 500 mg four times daily 1, 2
• Duration: 14 days mandatory—this improves eradication by approximately 5% compared to 7-10 day regimens 1

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth cannot be used 1:

• PPI: twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
• Amoxicillin: 1000 mg twice daily 1, 3
• Clarithromycin: 500 mg twice daily 1, 4
• Metronidazole: 500 mg twice daily 1

This regimen should only be used if local clarithromycin resistance is documented to be <15%, though bismuth quadruple therapy remains superior even in low-resistance areas 1

Critical Optimization Factors

• High-dose PPI twice daily is mandatory—esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs and standard doses 1, 5
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1
• 14-day duration is non-negotiable for optimal outcomes 1, 5

Second-Line Treatment After First-Line Failure

After failed first-line therapy, select a regimen based on which antibiotics were previously used 1:

If Bismuth Quadruple Therapy Failed First

Levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure) 1, 5:

• PPI: twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
• Amoxicillin: 1000 mg twice daily 1
• Levofloxacin: 500 mg once daily or 250 mg twice daily 1, 5

Critical caveat: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary), and the FDA recommends fluoroquinolones be used as a last choice due to serious side effects 1

If Triple Therapy Failed First

Bismuth quadruple therapy for 14 days (as detailed above) 1, 5

What NOT to Do

• Never repeat clarithromycin if it was in the failed regimen—resistance develops rapidly after exposure, and eradication rates drop from 90% to 20% with resistant strains 1
• Never repeat levofloxacin after prior exposure 1
• Avoid concomitant, sequential, or hybrid therapies—they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible 1, 5, 6, 7

If susceptibility testing is unavailable, consider:

Rifabutin Triple Therapy for 14 Days

• Rifabutin: 150 mg twice daily 1
• Amoxicillin: 1000 mg twice daily 1
• PPI: twice daily (esomeprazole or rabeprazole 40 mg preferred) 1
• Rifabutin resistance is rare, making this highly effective as rescue therapy 1

High-Dose Dual Therapy for 14 Days

• Amoxicillin: 2-3 grams daily in 3-4 split doses 1
• PPI: double standard dose twice daily (esomeprazole or rabeprazole 40 mg twice daily) 1
• This is an alternative rescue option when other therapies have been exhausted 1, 6

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, 5, 7

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

Special Populations

Patients with Penicillin Allergy

Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1, 2

Consider penicillin allergy testing to enable amoxicillin use, as most patients who report penicillin allergy are found not to have a true allergy 1

Common Pitfalls to Avoid

• Standard-dose PPI once daily is inadequate—always use twice-daily dosing to maximize gastric pH elevation 1, 5
• Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1
• Smoking increases risk of eradication failure (odds ratio 1.95) 1
• High BMI increases risk of failure due to lower drug concentrations at the gastric mucosal level 1
• Address compliance issues—more than 10% of patients are poor compliers, leading to much lower eradication rates 1

Managing Side Effects

Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota 1

Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance, though evidence for increasing eradication rates is limited 1, 5, 7