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

Recommended Quadruple Therapy Regimens for H. pylori Infection

Bismuth quadruple therapy is the preferred first-line regimen for H. pylori eradication, consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate four times daily, metronidazole 400-500mg three to four times daily, and tetracycline 500mg four times daily for 10-14 days. 1, 2

First-Line Treatment Options

• Bismuth quadruple therapy is strongly recommended as first-line treatment, especially in areas with high clarithromycin resistance (>15-20%), due to its effectiveness even against metronidazole-resistant strains 1
• The recommended duration for bismuth quadruple therapy is 14 days, unless 10 days has been proven locally to be equally effective 1
• Non-bismuth quadruple therapy (concomitant therapy) is an alternative first-line option in areas where bismuth is unavailable, consisting of PPI twice daily, amoxicillin 1000mg twice daily, metronidazole 500mg twice daily, and clarithromycin 500mg twice daily for 10-14 days 1
• Traditional triple therapy (PPI + clarithromycin + amoxicillin/metronidazole) should be abandoned in areas where clarithromycin resistance exceeds 15-20% 1

Optimizing Quadruple Therapy Efficacy

• High-dose PPI (twice daily) should be used to increase treatment efficacy, as this has been shown to improve eradication rates by 6-10% compared to standard doses 1, 2
• Extending treatment duration to 14 days rather than 7-10 days improves eradication success by approximately 5% 1
• Bismuth is particularly valuable because bacterial resistance to this compound is extremely rare, making bismuth quadruple therapy effective even against strains with metronidazole resistance 2, 3
• Consider adding probiotics as adjuvant therapy to reduce side effects, though evidence for this is limited 1, 2

Second-Line Treatment Options

• After failure of a clarithromycin-containing therapy, bismuth quadruple therapy is recommended as second-line treatment 1
• Levofloxacin-based triple therapy (PPI + amoxicillin + levofloxacin) is an alternative second-line option, consisting of PPI twice daily, amoxicillin 1000mg twice daily, and levofloxacin 500mg once daily or 250mg twice daily for 10-14 days 1, 2
• Rising rates of levofloxacin resistance should be taken into account when considering this option 1

Third-Line and Rescue Therapies

• After failure of second-line treatment, therapy should be guided by antimicrobial susceptibility testing whenever possible 1, 2
• Alternative rescue therapies include:
  • Rifabutin-containing triple therapy (PPI + amoxicillin + rifabutin) for 10 days 1
  • High-dose dual therapy (rabeprazole 20mg four times daily + amoxicillin 750mg four times daily) for 14 days 1

Important Considerations and Pitfalls

• Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance is likely to have developed 2, 4
• Always confirm eradication after treatment using either urea breath test or a validated monoclonal stool test (not serology) 1, 2
• The goal should be to succeed on the first attempt, thus avoiding retreatment and retesting, and reducing cost, anxiety, and negative impacts on other gut microbiota 1
• Sequential therapy (5 days of PPI + amoxicillin followed by 5 days of PPI + clarithromycin + metronidazole) is no longer recommended as it has shown inconsistent results across different populations 1