What is the recommended eradication regimen for a patient with confirmed Helicobacter pylori infection?

Recommended Eradication Regimen for Confirmed Helicobacter pylori Infection

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori eradication, consisting of a high-dose proton pump inhibitor (PPI) twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment: Bismuth Quadruple Therapy

The regimen achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it superior to traditional triple therapy in most clinical scenarios. 1, 2

Specific Dosing Protocol

• Esomeprazole 40 mg or rabeprazole 40 mg twice daily (preferred over other PPIs; increases cure rates by 8-12%) 1, 2
• Bismuth subsalicylate 262 mg (two tablets) 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 ~5% compared to shorter courses) 1, 2

Timing of Administration

• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1
• Take bismuth 30 minutes before meals and at bedtime 1
• Take metronidazole 30 minutes after meals 1

Alternative First-Line Option (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days can be used only in regions with documented clarithromycin resistance <15%: 1, 2

• Esomeprazole or rabeprazole 40 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1

However, clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making this option inappropriate in most regions without susceptibility testing. 1

Why Bismuth Quadruple Therapy Is Preferred

• No bacterial resistance to bismuth has been described 1
• Bismuth's synergistic effect overcomes metronidazole resistance in vitro 1
• Tetracycline and amoxicillin resistance remain rare (<5%) 1
• Uses antibiotics from the WHO "Access group" rather than "Watch group," supporting antimicrobial stewardship 1
• Effective even against strains with dual clarithromycin-metronidazole resistance 1

Second-Line Treatment After First-Line Failure

If bismuth quadruple therapy fails, levofloxacin triple therapy for 14 days is the next option (provided no prior fluoroquinolone exposure): 1, 2

• Esomeprazole or rabeprazole 40 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Levofloxacin 500 mg once daily 1

Never repeat clarithromycin if it was in a failed regimen—resistance develops rapidly after exposure, dropping eradication rates from 90% to 20%. 1

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 2

If susceptibility testing is unavailable:

• Rifabutin triple therapy for 14 days: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + high-dose PPI twice daily 1, 2
• High-dose dual therapy for 14 days: amoxicillin 2-3 g daily in 3-4 divided doses + high-dose PPI twice daily 1

Special Populations

Penicillin Allergy

Bismuth quadruple therapy is the first choice because it contains tetracycline, not amoxicillin. 1

Consider penicillin allergy testing after first-line failure, as most patients who report penicillin allergy are found not to have a true allergy. 1

Elderly Patients

Tetracycline is not contraindicated by age alone; bismuth quadruple therapy remains the preferred first-line regimen. 1

Shared decision-making is essential after multiple failures, weighing benefits against adverse-effect risk. 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

Discontinue PPI at least 2 weeks before testing. 1, 2

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

Critical Pitfalls to Avoid

• Never use standard-dose PPI once daily—this is a major cause of treatment failure 1
• Never use pantoprazole—40 mg provides acid suppression equivalent to only 9 mg omeprazole, which is inadequate 1, 2
• Never shorten therapy below 14 days 1, 2
• Never use clarithromycin-based triple therapy empirically when regional resistance exceeds 15% (which is now most regions) 1
• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin 1
• Avoid concomitant, sequential, or hybrid therapies—they expose patients to unnecessary antibiotics that contribute to global resistance without therapeutic benefit 1

Patient Factors Affecting Success

• Smoking increases eradication failure risk (OR 1.95) 1
• High BMI reduces drug concentrations at the gastric mucosal level 1
• Poor compliance (>10% of patients) dramatically reduces eradication rates 1

Provide clear education on regimen rationale, dosing, expected adverse events, and the importance of completing the full 14-day course to improve adherence. 1