What is the recommended treatment regimen for a patient with a confirmed diagnosis of H. Pylori infection?

Treatment for H. Pylori

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment Regimen

Bismuth quadruple therapy is recommended because it avoids clarithromycin entirely and maintains 80-90% eradication rates even in areas with high antibiotic resistance. 1, 3 This regimen is superior to traditional triple therapy, which now achieves only 70% eradication rates in most regions due to clarithromycin resistance exceeding 15-20%. 1, 3

Standard Bismuth Quadruple Therapy Components:

• PPI (esomeprazole or rabeprazole 40 mg) twice daily - taken 30 minutes before meals 1, 3
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 1, 3
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 3
• Tetracycline 500 mg four times daily 1, 3
• Duration: 14 days mandatory 1, 2

The 14-day duration is critical—it improves eradication success by approximately 5% compared to shorter regimens. 1, 2 High-dose PPI twice daily (not standard once-daily dosing) increases eradication success by an additional 5% compared to standard dosing. 1, 2

Alternative First-Line Options (When Bismuth Unavailable):

Concomitant non-bismuth quadruple therapy can be used when bismuth is not available: 1, 3

• PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days 1, 3

However, this should only be considered in areas with documented clarithromycin resistance below 15%, which is now rare in most of North America and Europe. 1, 3

Second-Line Treatment After First-Line Failure

If bismuth quadruple therapy fails, levofloxacin triple therapy for 14 days is the preferred second-line option (provided the patient has no prior fluoroquinolone exposure): 1, 2

• PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Levofloxacin 500 mg once daily 1
• Duration: 14 days 1

Critical pitfall: Never repeat antibiotics that failed previously, especially clarithromycin or levofloxacin, as resistance develops rapidly after exposure. 1, 3 When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20%. 1

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 3

Rescue options include:

• Rifabutin triple therapy: Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days 1, 3
• High-dose dual therapy: Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days 1, 3

Confirmation of Eradication (Test-of-Cure)

All patients must undergo test-of-cure at least 4 weeks after completing treatment to ensure successful eradication. 1, 2 This is non-negotiable, as persistent infection leads to complications and antibiotic resistance. 1

Testing Requirements:

• Preferred methods: Urea breath test (88-95% sensitivity, 95-100% specificity) or laboratory-based validated monoclonal stool antigen test (>90% sensitivity and specificity) 1
• Critical timing: Test at least 4 weeks after treatment completion AND at least 2 weeks after PPI discontinuation 1, 2
• Never use serology for test-of-cure—antibodies persist long after successful treatment 1

Special Clinical Contexts

Penicillin Allergy:

Bismuth quadruple therapy is the first choice since it contains tetracycline, not amoxicillin. 1, 2 Consider penicillin allergy testing to enable amoxicillin use, as most patients with reported penicillin allergy are found not to have true allergy. 1

Bleeding Peptic Ulcer:

Start eradication therapy immediately when oral feeding is reintroduced (after 72-96 hours of intravenous PPI). 1 Eradication reduces rebleeding rates from 26% to near zero. 1

Gastric MALT Lymphoma:

H. pylori eradication is first-line treatment for low-grade gastric MALT lymphoma, achieving 60-80% cure rates in early-stage cases. 1 Confirmation of successful eradication is mandatory in these patients. 1

Critical Pitfalls to Avoid

Never perform H. pylori testing while a patient is taking PPIs, antibiotics, or bismuth—bacterial suppression yields false-negative results. 1, 2 PPIs must be discontinued at least 2 weeks before testing. 1, 2

Antibiotic resistance is the most important factor responsible for eradication failure. 1, 2 Clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making traditional triple therapy unacceptably ineffective. 1, 3

Patient compliance is crucial—incomplete treatment leads to antibiotic resistance and treatment failure. 1, 2 More than 10% of patients are poor compliers, resulting in much lower eradication rates. 1 Ensure patients understand the importance of completing the full 14-day course. 1, 2

Avoid concomitant, sequential, or hybrid therapies—these include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit. 1