What is the recommended treatment for H. Pylori (Helicobacter Pylori) infection?

H. Pylori Infection Treatment

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection in North America, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

Why Bismuth Quadruple Therapy is Preferred

The shift away from traditional triple therapy is driven by rising antibiotic resistance:

• Clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 1, 2
• When H. pylori strains are clarithromycin-resistant, eradication rates with triple therapy drop to approximately 20% compared to 90% with susceptible strains 1
• Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect with other antibiotics 1, 2
• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare 1

Specific First-Line Regimen

Bismuth Quadruple Therapy (14 days): 1, 2

• PPI (standard dose) twice daily, taken 30 minutes before meals 1
• Bismuth subsalicylate 262 mg (2 tablets) four times daily OR bismuth subcitrate 120 mg four times daily 1, 2
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 2
• Tetracycline 500 mg four times daily 1, 2

Critical Optimization Factors

• Use high-dose PPI twice daily—esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs 1, 2
• 14-day duration is mandatory—extending from 7 to 14 days improves eradication success by approximately 5% 1, 2
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1

Alternative First-Line Options (When Bismuth Unavailable)

Concomitant Non-Bismuth Quadruple Therapy (14 days): 1, 2

• PPI twice daily
• Amoxicillin 1000 mg twice daily 3
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This regimen should only be used when bismuth is truly unavailable, as it includes clarithromycin which faces increasing resistance 1, 2

Second-Line Treatment After First-Line Failure

After bismuth quadruple therapy failure: 1, 2

Levofloxacin Triple Therapy (14 days):

• PPI twice daily
• Amoxicillin 1000 mg twice daily 3
• Levofloxacin 500 mg once daily OR 250 mg twice daily

Critical caveat: Only use levofloxacin if the patient has no prior fluoroquinolone exposure, as resistance rates are rising (11-30% primary, 19-30% secondary) 1, 4

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 2, 5

If susceptibility testing is unavailable: 1, 2

Rifabutin Triple Therapy (14 days):

• Rifabutin 150 mg twice daily
• Amoxicillin 1000 mg twice daily 3
• PPI twice daily

High-Dose Dual Amoxicillin-PPI Therapy (14 days):

• Amoxicillin 2-3 grams daily in 3-4 split doses 3
• High-dose PPI (double standard dose) twice daily

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using urea breath test or validated monoclonal stool antigen test. 1, 2

• Discontinue PPI at least 2 weeks before testing 1, 2
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1

Common Pitfalls and How to Avoid Them

Antibiotic Selection Errors:

• Never repeat clarithromycin or levofloxacin if the patient has prior exposure to these antibiotics (for any indication), as resistance develops rapidly 1, 2
• Avoid assuming low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1

Dosing Errors:

• Standard-dose PPI once daily is inadequate—always use twice-daily dosing 1, 2
• Do not prescribe 7-10 day regimens—14 days is mandatory for optimal results 1, 2

Patient Factors:

• Smoking increases eradication failure risk (odds ratio 1.95) 1, 2
• High BMI increases failure risk due to lower drug concentrations at the gastric mucosal level 1, 2
• Address compliance issues—more than 10% of patients are poor compliers 1

Managing Side Effects:

• Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota 1
• Consider adjunctive probiotics to reduce diarrhea risk and improve compliance, though probiotics have no solid evidence to increase eradication rates 1, 2

Special Populations

Penicillin allergy: Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1, 2

Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains extremely rare (<5%) 1

Renal impairment: Patients with GFR less than 30 mL/min should NOT receive the 875 mg amoxicillin dose; adjust dosing per renal function 3