What is the recommended quadruple therapy regimen for H. pylori (Helicobacter pylori) eradication?

Recommended Quadruple Therapy for H. pylori Eradication

Bismuth quadruple therapy for 14 days is the recommended first-line quadruple therapy regimen for Helicobacter pylori eradication, consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate/subcitrate four times daily, metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily. 1, 2

First-Line Quadruple Therapy Options

Bismuth-Based Quadruple Therapy

• Standard regimen (PBMT): PPI twice daily, bismuth subsalicylate/subcitrate four times daily, metronidazole 500 mg three to four times daily, and tetracycline 500 mg four times daily for 14 days 1, 2
• This regimen is preferred in areas with high clarithromycin resistance (≥15%) and is effective even against metronidazole-resistant strains 2, 3
• Bismuth quadruple therapy avoids the issue of clarithromycin resistance and is recommended by all major guidelines as first-line treatment 2

Non-Bismuth Concomitant Quadruple Therapy

• Alternative when bismuth is unavailable: PPI twice daily, amoxicillin 1000 mg twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily for 14 days 2, 1
• This regimen is particularly useful in areas with high clarithromycin resistance where bismuth is not available 2, 3

Treatment Duration and Dosing Considerations

• 14-day duration is recommended for all quadruple therapy regimens to maximize eradication rates 2, 1
• High-dose PPI (twice standard dose) improves eradication rates by increasing gastric pH, which enhances antibiotic efficacy 1, 3
• Optimal PPI dosing is 30 minutes before meals on an empty stomach 2

Treatment Selection Based on Antibiotic Resistance

• The choice of quadruple therapy should be guided by local antibiotic resistance patterns and the patient's previous antibiotic exposure 1, 2
• In areas with high dual resistance to clarithromycin and metronidazole, bismuth quadruple therapy is strongly preferred 2, 3
• Susceptibility testing should be considered after two failed eradication attempts 2, 1

Special Considerations

• For patients with penicillin allergy, amoxicillin can be replaced with tetracycline in appropriate regimens 1
• After failure of a clarithromycin-containing regimen, avoid using clarithromycin in subsequent treatment attempts 2
• Probiotics may be used as adjunctive therapy to reduce antibiotic side effects and potentially improve eradication rates 1, 3

Verification of Eradication

• Confirmation of eradication should be performed using urea breath test or stool antigen test at least 8 weeks after completion of therapy 1
• Patients should discontinue PPIs at least 2 weeks before testing to avoid false-negative results 1

Treatment Failure Management

• After first-line treatment failure, second-line options include:
  • Bismuth quadruple therapy (if not previously used) 1, 2
  • Levofloxacin triple therapy: PPI twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily or 250 mg twice daily for 14 days 1, 3
• For multiple treatment failures, antimicrobial susceptibility testing should guide therapy selection whenever possible 2, 1

Emerging Approaches

• Potassium-competitive acid blockers (P-CABs) like vonoprazan may improve eradication rates compared to traditional PPIs 3, 4
• Rifabutin-based triple therapy may be considered for patients with multiple treatment failures, as rifabutin resistance is rare 2, 5