What antibiotics (ATB) can be used to treat Helicobacter pylori (H. pylori) infection in a patient with a penicillin allergy?

Treatment of Helicobacter Pylori in Patients with Penicillin Allergy

For patients with penicillin allergy, bismuth quadruple therapy is the recommended first-line treatment for Helicobacter pylori infection due to its superior efficacy compared to other regimens. 1

First-Line Treatment Options

• Bismuth quadruple therapy: Bismuth subsalicylate + metronidazole + tetracycline + PPI for 14 days is the preferred first-line regimen for penicillin-allergic patients 1
• This regimen achieves higher eradication rates (74-75%) compared to clarithromycin-metronidazole-PPI triple therapy (57-59%) in penicillin-allergic patients 2
• The Toronto Consensus, American College of Gastroenterology (ACG), and Maastricht V/Florence guidelines all recommend bismuth quadruple therapy as the preferred option for patients with penicillin allergy 1

Second-Line Treatment Options

• Levofloxacin-based triple therapy: PPI + clarithromycin + levofloxacin for 10 days is recommended after failure of bismuth quadruple therapy 1
• This regimen has shown 64% eradication rates in penicillin-allergic patients who failed first-line therapy 2
• All three major guidelines (Toronto, ACG, Maastricht) recommend levofloxacin-based therapy as a rescue option 1

Third-Line and Beyond

• Susceptibility testing should be strongly considered after failure of second-line therapy to guide subsequent treatment selection 1
• Rifabutin-based therapy (PPI + rifabutin + clarithromycin) should be restricted to patients who have failed multiple previous regimens due to potential myelotoxicity 1
• The Toronto Consensus recommends rifabutin only after three failed attempts, while other guidelines position it as third or fourth line 1

Important Considerations

• Allergy testing: For patients with suspected penicillin allergy who fail first-line therapy, referral for penicillin allergy testing is recommended as most patients with reported penicillin allergy do not have true allergy 1
• Antibiotic resistance: Avoid reusing antibiotics that have previously failed, particularly clarithromycin and levofloxacin, as resistance develops rapidly after exposure 1
• Treatment duration: 14-day regimens are preferred over 10-day regimens for higher eradication rates 1

Emerging Options

• Susceptibility-guided therapy has shown high efficacy (92.9% by intention-to-treat analysis) in penicillin-allergic patients when available 3
• Vonoprazan-based therapy (Vonoprazan + clarithromycin + metronidazole) has demonstrated excellent eradication rates in penicillin-allergic patients in recent studies, but availability may be limited 4

Regimens to Avoid

• PPI-clarithromycin-rifabutin has shown poor efficacy (11-22% eradication) and high rates of adverse effects (89%) including myelotoxicity 2, 5
• PPI-clarithromycin-metronidazole as first-line therapy achieves suboptimal eradication rates (57-59%) and should be avoided when bismuth quadruple therapy is available 2

Practical Algorithm for H. pylori Treatment in Penicillin-Allergic Patients

1. First-line: Bismuth quadruple therapy for 14 days 1
2. If first-line fails: Levofloxacin-based triple therapy for 10 days 1
3. If second-line fails: Consider penicillin allergy testing 1
4. If true penicillin allergy confirmed: Pursue susceptibility testing if available and consider rifabutin-based therapy as a last resort 1