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

Bismuth Quadruple Therapy is the Recommended First-Line Treatment for H. pylori Infection

The recommended quadruple therapy regimen for H. pylori infection is bismuth quadruple therapy consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate, metronidazole, and tetracycline for 14 days. 1, 2

First-Line Treatment Options

• Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection due to increasing global antibiotic resistance patterns 1, 3
• The standard bismuth quadruple therapy consists of:
  • PPI (twice daily)
  • Bismuth subsalicylate
  • Metronidazole
  • Tetracycline
  • Duration: 14 days 1, 2
• In areas with low clarithromycin resistance (<15%), triple therapy using a PPI with clarithromycin and amoxicillin (or metronidazole) for 10-14 days may be considered as an alternative 1, 2

Rationale for Bismuth Quadruple Therapy

• Clarithromycin resistance has increased globally, making traditional triple therapy less effective in many regions 1, 2
• Bismuth is valuable because bacterial resistance to this compound is extremely rare, making bismuth quadruple therapy effective even against strains resistant to metronidazole 1
• The American College of Gastroenterology recommends bismuth quadruple therapy for 14 days as the preferred regimen when antibiotic susceptibility is unknown 3

Optimizing Treatment Success

• High-dose PPI (twice daily) significantly increases the efficacy of eradication therapy by 6-10% compared to standard doses 1, 2
• Extending treatment duration to 14 days improves eradication success by approximately 5% compared to shorter durations 1, 2
• The stomach's acidity affects antibiotic efficacy, which is why PPIs are a crucial component of all H. pylori treatment regimens 1

Alternative Quadruple Therapy Options

• Concomitant (non-bismuth quadruple) therapy: PPI + clarithromycin + amoxicillin + metronidazole for 10-14 days is an alternative when bismuth is not available 1
• However, the American Gastroenterological Association recommends avoiding concomitant, sequential, or hybrid therapies as they include unnecessary antibiotics that contribute to global antibiotic resistance 1

Second-Line Treatment Options

• After failure of first-line therapy, an alternative regimen should be selected based on prior antibiotic exposure 1
• Levofloxacin-containing triple therapy is a recommended second-line option in areas with low levofloxacin resistance 1
• After two failed eradication attempts, antibiotic susceptibility testing is recommended to guide further treatment 1, 4

Common Pitfalls and Caveats

• Inadequate PPI dosing significantly reduces H. pylori treatment efficacy; always use high-dose (twice daily) PPI 2
• Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin 1
• Diarrhea occurs in 21-41% of patients during the first week of H. pylori eradication therapy due to disruption of normal gut microbiota 1
• 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, 2

FDA-Approved Regimens

• Triple therapy: 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily for 14 days 5
• Dual therapy: 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily for 14 days 5