What is the recommended treatment for H pylori infection?

H. pylori Treatment

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

First-Line Treatment Regimen

The preferred first-line regimen is bismuth quadruple therapy for 14 days: 1, 2

• PPI (high-dose): Esomeprazole or rabeprazole 40 mg twice daily, taken 30 minutes before meals on an empty stomach 1
• Bismuth subsalicylate: 262 mg (2 tablets) four times daily 1
• Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline: 500 mg four times daily 1

This regimen achieves 80-90% eradication rates even against clarithromycin-resistant and metronidazole-resistant strains due to bismuth's synergistic effect, and bacterial resistance to bismuth is extremely rare. 1, 2

Alternative First-Line Option (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days: 1

• PPI (high-dose): Twice daily 1
• Amoxicillin: 1000 mg twice daily 1, 3
• Clarithromycin: 500 mg twice daily 1
• Metronidazole: 500 mg twice daily 1

This regimen should only be used when bismuth is unavailable and in areas with clarithromycin resistance <15%. 1

Critical Optimization Factors

Treatment Duration

• 14 days is mandatory for all regimens, as this improves eradication success by approximately 5% compared to 7-10 day regimens. 1, 4

PPI Dosing

• High-dose PPI twice daily is essential, not standard once-daily dosing, as this increases cure rates by 6-12%. 1, 5
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by an additional 8-12% compared to other PPIs. 1
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids. 1

Antibiotic Resistance Considerations

• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy unacceptable as first-line treatment. 1
• When clarithromycin-resistant strains are present, eradication rates with triple therapy drop from 90% to approximately 20%. 1
• Standard PPI-clarithromycin-amoxicillin triple therapy should be abandoned in most regions due to high resistance rates. 1

Second-Line Treatment After First-Line Failure

After bismuth quadruple therapy failure, use levofloxacin-based triple therapy for 14 days (if no prior fluoroquinolone exposure): 1, 2

• PPI (high-dose): Twice daily 1
• Amoxicillin: 1000 mg twice daily 1
• Levofloxacin: 500 mg once daily or 250 mg twice daily 1

After clarithromycin-based therapy failure, use bismuth quadruple therapy for 14 days (if not previously used). 1, 2

Critical Principle for Second-Line Therapy

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, as resistance develops rapidly after exposure. 1, 2

Third-Line and Rescue Therapies

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

Rescue Options (in order of preference):

Rifabutin-based triple therapy for 14 days: 1, 2

• Rifabutin 150 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• PPI (high-dose) twice daily 1
• Rifabutin resistance is extremely rare, making this highly effective for persistent infections. 1, 2

High-dose dual amoxicillin-PPI therapy for 14 days: 1

• Amoxicillin 2-3 grams daily in 3-4 split doses 1
• PPI (double standard dose) twice daily 1

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test: 1, 2, 5

• Test at least 4 weeks after completion of therapy 1, 2
• Discontinue PPI at least 2 weeks before testing 1, 2
• Never use serology to confirm eradication, as antibodies persist long after successful treatment. 1

Special Populations

Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1
• Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare (<5%). 1

Renal Impairment

• Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose. 3
• For GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours 3
• For GFR <10 mL/min: 500 mg or 250 mg every 24 hours 3

Common Pitfalls and How to Avoid Them

• Inadequate PPI dosing: Always use high-dose (twice daily) PPI; standard once-daily dosing significantly reduces efficacy. 1, 2, 5
• Assuming low clarithromycin resistance: Never assume low resistance without local surveillance data—most regions now have high resistance rates. 1
• Repeating failed antibiotics: Avoid re-using clarithromycin or levofloxacin after failure, as cross-resistance is universal. 1, 2
• Insufficient treatment duration: 7-10 day regimens are inadequate; always use 14 days. 1, 4
• Poor compliance: Diarrhea occurs in 21-41% of patients during the first week; consider adjunctive probiotics to reduce side effects and improve compliance. 1

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95). 1
• High BMI/obesity increases risk of failure due to lower drug concentrations at the gastric mucosal level. 1
• Poor compliance accounts for >10% of treatment failures; address this proactively. 1