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

H. Pylori Treatment

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in North America, consisting of a PPI twice daily, bismuth subsalicylate (262 mg four times daily or 120 mg subcitrate four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily). 1, 2, 3

First-Line Treatment Selection

The choice of first-line therapy depends critically on local clarithromycin resistance patterns, which now exceed 15% in most of North America, Central, Western, and Southern Europe 1:

In Areas of High Clarithromycin Resistance (≥15%)

• Bismuth quadruple therapy for 14 days is the first choice, achieving 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect 1, 2, 3
• This regimen avoids clarithromycin entirely, which is essential since clarithromycin resistance drops eradication rates from 90% to approximately 20% 1
• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare 1

Alternative First-Line Options (When Bismuth Unavailable)

• Concomitant non-bismuth quadruple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily 1, 2
• This regimen administers all antibiotics simultaneously, preventing resistance development during treatment 1
• Rifabutin triple therapy for 14 days (in patients without penicillin allergy): rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily 1, 3

In Areas of Low Clarithromycin Resistance (<15%)

• Standard triple therapy may be considered: PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days 1, 2, 4
• However, do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1

Critical Treatment Optimization Factors

PPI Dosing

• High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate 1, 2, 3
• Take PPI 30 minutes before meals on an empty stomach 1
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% compared to other PPIs 1

Treatment Duration

• 14 days is superior to 7-10 day regimens, improving eradication success by approximately 5% 1, 2, 4, 3
• The 2024 American College of Gastroenterology guideline strongly recommends 14 days to maximize first-attempt success 3

Medication Timing

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 5

Second-Line Treatment After First Failure

After first-line treatment failure, avoid repeating antibiotics previously used, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1, 2, 3

Preferred Second-Line Options

• "Optimized" bismuth quadruple therapy for 14 days if not used as first-line treatment 3
• Levofloxacin triple therapy for 14 days (in areas with low levofloxacin resistance): PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily or 250 mg twice daily 6, 1, 2, 4
  • However, levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary) 1
  • The FDA recommends fluoroquinolones be used as a last choice due to serious side effects 1

Third-Line and Rescue Therapies

After two treatment failures, antibiotic susceptibility testing should guide further treatment whenever possible. 6, 1, 2, 3

When Susceptibility Testing Unavailable

• Rifabutin triple therapy for 14 days: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily 6, 1, 3
• High-dose dual amoxicillin-PPI therapy: amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days 1, 3
• Use antibiotics not previously used: amoxicillin, tetracycline, and bismuth can be re-used because resistance remains rare 1

Special Populations

Patients with Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1, 2
• Avoid defaulting to clarithromycin + metronidazole triple therapy, which is frequently ineffective 6, 7

Patients with Renal Impairment

• For GFR 10-30 mL/min: reduce amoxicillin to 500 mg or 250 mg every 12 hours 5
• For GFR <10 mL/min: reduce amoxicillin to 500 mg or 250 mg every 24 hours 5
• Patients on hemodialysis require an additional dose during and at the end of dialysis 5

Confirmation of Eradication

• Test for eradication success at least 4 weeks after completion of therapy using urea breath test or validated monoclonal stool antigen test 6, 1, 2
• Discontinue PPI at least 2 weeks before testing 1
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1

Common Pitfalls to Avoid

• Do not use standard triple therapy empirically in areas where clarithromycin resistance exceeds 15-20% 1, 4, 7
• Do not prescribe treatment for only 7-10 days—this is a common error identified in the European Registry, occurring in 69% of cases 7
• Do not use low-dose PPI once daily—this occurred in 48% of cases in the European Registry and significantly reduces efficacy 7
• Do not repeat clarithromycin if the patient has prior macrolide exposure for any indication—cross-resistance is universal within the macrolide family 1
• Do not fail to check eradication success—this oversight occurred in 6% of cases in the European Registry 7

Adjunctive Measures

• Consider probiotics as adjuvant therapy to reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve compliance 1, 4
• Address patient factors affecting success: smoking increases eradication failure risk (OR 1.95), and high BMI reduces drug concentrations at the gastric mucosal level 1
• Ensure compliance—more than 10% of patients are poor compliers, leading to much lower eradication rates 1