What is the recommended triple therapy regimen for Helicobacter pylori (H. pylori) eradication in a patient with a penicillin allergy?

From the Guidelines

For patients with penicillin allergy who need H. pylori eradication therapy, I recommend a bismuth quadruple therapy consisting of a proton pump inhibitor, bismuth subsalicylate, metronidazole, and tetracycline for 14 days, as this regimen has been shown to be effective and avoids all beta-lactam antibiotics including penicillins 1.

Key Considerations

• The bismuth quadruple therapy is preferred over clarithromycin-based triple therapy with metronidazole due to its superiority in a prospective study, as noted by the Toronto Consensus 1.
• The regimen should include a proton pump inhibitor (such as omeprazole 20 mg twice daily), bismuth subsalicylate (262 mg, 2 tablets, four times daily), metronidazole (500 mg three times daily), and tetracycline (500 mg four times daily) for 14 days.
• Alternatively, if tetracycline is unavailable, a levofloxacin-based triple therapy can be used, consisting of a proton pump inhibitor (standard dose twice daily), levofloxacin (500 mg once daily), and clarithromycin (500 mg twice daily) for 14 days, as suggested by the ACG 1.

Important Notes

• Before starting treatment, it's essential to confirm the penicillin allergy, as many patients with reported allergies can actually tolerate penicillins.
• For patients with severe penicillin allergy (anaphylaxis), avoid all beta-lactams completely.
• Eradication should be confirmed with a urea breath test, stool antigen test, or endoscopic biopsy at least 4 weeks after completing therapy and at least 2 weeks after stopping proton pump inhibitors.

Mechanism of Action

• Bismuth disrupts the bacterial cell membrane, metronidazole and levofloxacin interfere with DNA synthesis, and tetracycline and clarithromycin inhibit protein synthesis, making these regimens effective against H. pylori 1.

From the Research

Triple Therapy for H. pylori with Penicillin Allergy

• The most effective option for first-line treatment appears to be Bismuth-based quadruple therapy for 10-14 days 2.
• A triple combination with a PPI, clarithromycin, and metronidazole is often prescribed as the first option, but its efficacy is lower, around 69% 3.
• Second-line treatment with Levoflaxacin-based triple therapy for 10 days is also an option, with an efficacy of around 71-73% 2, 3, 4.
• In patients allergic to penicillin, a quadruple regimen with PPI, bismuth, tetracycline, and metronidazole seems to be a better option, with an efficacy of around 91% 3.
• Dual therapies containing an antibiotic plus a proton pump inhibitor or vonoprazan may also be effective, with eradication rates of around 86-93% 5.

Treatment Options

• First-line treatment:
  • Bismuth-based quadruple therapy for 10-14 days 2
  • Triple combination with PPI, clarithromycin, and metronidazole for 7-10 days 3, 6, 4
• Second-line treatment:
  • Levoflaxacin-based triple therapy for 10 days 2, 3, 4
  • Quadruple regimen with PPI, bismuth, tetracycline, and metronidazole for 10-14 days 3
• Third-line treatment:
  • Quadruple regimen with PPI, bismuth, tetracycline, and metronidazole for 10-14 days 3
  • Rifabutin-based regimen, but its efficacy is lower and it is poorly tolerated 6

Efficacy and Safety

• The efficacy of different treatment regimens varies, with Bismuth-based quadruple therapy being the most effective option 2, 3.
• The safety of different treatment regimens also varies, with some regimens causing more adverse events than others 3, 6, 4.