From the Guidelines
Quadruple therapy for H. pylori infection should consist of a concomitant non-bismuth quadruple regimen, including a PPI, amoxicillin 1000 mg twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily, taken for 14 days, as this regimen is recommended by all guidelines and has shown superiority over other regimens 1.
Key Components of Quadruple Therapy
- A proton pump inhibitor (PPI) such as omeprazole 20mg or esomeprazole 40mg twice daily
- Amoxicillin 1000 mg twice daily
- Metronidazole 500 mg twice daily
- Clarithromycin 500 mg twice daily
Duration of Therapy
The preferred length of first-line therapy is 14 days, as it has shown superiority over 10-day regimens 1.
Special Considerations
- In patients with true penicillin allergy, bismuth quadruple therapy is recommended by the Toronto Consensus, while the ACG and Maastricht V/Florence recommend either clarithromycin-based triple therapy with metronidazole or bismuth quadruple therapy 1.
- Patients should be advised to complete the full course of treatment even if symptoms improve, avoid alcohol during metronidazole treatment, and take medications as directed.
Confirmation of Eradication
Confirmation of eradication should be performed at least 4 weeks after therapy completion using urea breath test, stool antigen test, or endoscopic biopsy.
Alternative Regimens
Alternative regimens, such as bismuth quadruple therapy, may be considered in certain situations, but concomitant non-bismuth quadruple therapy is generally recommended as first-line treatment 1.
From the Research
H pylori Quadruple Therapy
- Quadruple therapy for H. pylori infection has been shown to be effective in several studies 2, 3, 4, 5.
- A study from 1997 found that twice a day quadruple therapy (bismuth subsalicylate, tetracycline, metronidazole plus lansoprazole) had a cure rate of 70% for intention-to-treat, with higher cure rates for metronidazole-sensitive strains (89.7%) compared to metronidazole-resistant strains (41.2%) 2.
- Another study from 1998 found that a 5-day quadruple therapy (amoxicillin, metronidazole, omeprazole, and clarithromycin) had an eradication rate of 96% for patients without previous dual therapy and 92% for patients with previous dual therapy 3.
- A 2023 review found that standard bismuth quadruple therapy, fluoroquinolone-containing triple or quadruple therapy, or proton pump inhibitor-amoxicillin high-dose dual therapy are recommended as second-line treatments for H. pylori infection, with per-protocol eradication rates exceeding 85% in most geographic areas 6.
- A 2004 study found that twice daily (mid-day and evening) quadruple therapy for 14 days had a success rate of 92.3%, including 96.2% of those with metronidazole-susceptible strains and 83.3% of those with metronidazole-resistant H. pylori 4.
- A 2010 randomized controlled trial found that a new quadruple therapy regimen (azithromycin, ofloxacin, bismuth, and omeprazole) had a higher eradication rate (77.3%) compared to the standard second-line treatment (64.5%) 5.
Quadruple Therapy Regimens
- Different quadruple therapy regimens have been studied, including:
- Bismuth subsalicylate, tetracycline, metronidazole, and lansoprazole 2
- Amoxicillin, metronidazole, omeprazole, and clarithromycin 3
- Azithromycin, ofloxacin, bismuth, and omeprazole 5
- Tetracycline, levofloxacin, bismuth, and proton pump inhibitor 6
- The choice of regimen may depend on factors such as antibiotic resistance patterns, patient compliance, and side effect profiles.
Efficacy and Safety
- Quadruple therapy regimens have been shown to be effective and safe for the treatment of H. pylori infection, with eradication rates ranging from 70% to 96% 2, 3, 4, 5.
- Side effects have been reported, but are generally mild to moderate, with few patients discontinuing treatment due to adverse events 2, 4, 5.