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

H. pylori Treatment

First-Line Treatment Recommendation

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

This recommendation is based on:

• Increasing global clarithromycin resistance now exceeds 15% in most regions, making traditional triple therapy unacceptably ineffective with eradication rates dropping to approximately 20% for resistant strains compared to 90% for susceptible strains 1, 2
• Bismuth quadruple therapy achieves 80-90% eradication rates even against strains with dual resistance to clarithromycin and metronidazole due to bismuth's synergistic effect 1, 2
• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare (<5%) 1, 2, 3

Critical Optimization Factors

• High-dose PPI twice daily is mandatory (not standard once-daily dosing), as this increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by an additional 8-12% compared to other PPIs 1, 2
• Take PPI 30 minutes before meals on an empty stomach without concomitant antacids 1, 4
• 14-day duration is superior to shorter regimens by approximately 5%, maximizing first-attempt success 1, 2, 5

Alternative First-Line Option (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 2, 3, 5

• This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment 2
• Should only be used when bismuth is unavailable, as it includes clarithromycin which has increasing resistance rates 2, 3

Second-Line Treatment After First-Line Failure

After bismuth quadruple therapy failure, levofloxacin-based triple therapy for 14 days is recommended (if no prior fluoroquinolone exposure): PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 2, 6

Critical caveat: Rising levofloxacin resistance rates (11-30% primary, 19-30% secondary) mean this should not be used empirically as first-line therapy 1, 2

Alternative second-line option: If bismuth quadruple therapy was not used first-line, it can be used as second-line treatment for 14 days 1, 2

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 2, 3

When susceptibility testing is unavailable:

• Rifabutin-based triple therapy for 14 days: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily 1, 2

  • Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections 1, 2
  • Should be reserved for patients who have failed previous eradication attempts 1

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

  • Alternative rescue therapy when other options have been exhausted 1

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2, 3

• Never use serology to confirm eradication as antibodies may persist long after successful treatment 1, 2

Common Pitfalls and How to Avoid Them

• Inadequate PPI dosing is the most common error: Always use high-dose (twice daily) PPI, preferably esomeprazole or rabeprazole 40 mg 1, 2
• Never repeat antibiotics previously used, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2
• Do not use 7-10 day regimens: 14 days is now the standard duration for all regimens 1, 2, 5
• Avoid standard triple therapy (PPI + clarithromycin + amoxicillin) unless local clarithromycin resistance is documented to be <15%, which is rare in most regions 2, 3
• Address compliance issues: More than 10% of patients are poor compliers, leading to much lower eradication rates 1
• Patient factors affecting success: Smoking increases failure risk (OR 1.95), and high BMI reduces drug concentrations at the gastric mucosal level 1

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 1
• Pediatric patients: Fluoroquinolones and tetracyclines should not be used, limiting treatment options 2
• Renal impairment: Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose 4

Adjunctive Therapies

Probiotics can be used as adjunctive treatment to reduce side effects, particularly antibiotic-associated diarrhea (which occurs in 21-41% of patients), though evidence for increased eradication rates is limited 2, 3, 6