What is the recommended treatment 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, consisting of a high-dose PPI twice daily, bismuth subsalicylate (262 mg four times daily or bismuth subcitrate 120 mg four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily). 1, 2

Why Bismuth Quadruple Therapy is First-Line

• Clarithromycin resistance now exceeds 15% in most regions globally, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 2, 3
• 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
• Bacterial resistance to bismuth is extremely rare, and tetracycline resistance remains rare in most regions 2, 3
• This regimen uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 3

Critical Treatment Optimization Factors

• High-dose PPI twice daily is mandatory—take 30 minutes before meals on an empty stomach; this increases eradication efficacy by 6-10% compared to standard dosing 1, 2
• 14-day duration is superior to shorter regimens, improving eradication success by approximately 5% compared to 7-10 day courses 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% compared to other PPIs 3
• Confirm patients are taking medications correctly to maximize absorption and compliance 1

Alternative First-Line Option (When Bismuth is 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
• This regimen should only be used in areas with clarithromycin resistance <15%, which is now rare in most regions 2, 3
• Administering all four medications simultaneously prevents resistance development during treatment, unlike sequential therapy 3

Second-Line Treatment After First-Line Failure

After bismuth quadruple therapy failure, use levofloxacin-based triple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 2

• Do not use levofloxacin if the patient has had prior fluoroquinolone exposure for any indication, as resistance rates are 11-30% (primary) and 19-30% (secondary) 3
• The FDA recommends fluoroquinolones be used as a last choice due to risk of serious side effects 3

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

Third-Line and Rescue Therapies

• After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible 1, 2
• Rifabutin-based triple therapy for 14 days: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily 1, 3
  • Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections 1
  • Reserve rifabutin for patients who have failed previous eradication attempts 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 3

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

Special Populations

• Penicillin allergy: Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 3
• Pediatric patients: Treatment should only be conducted by pediatricians in specialist centers; avoid fluoroquinolones and tetracyclines in children 2, 3
• Severe renal impairment (GFR <30 mL/min): Adjust amoxicillin dosing—do not use 875 mg dose; use 500 mg or 250 mg every 12-24 hours depending on severity 4

Critical Pitfalls to Avoid

• Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance develops rapidly after exposure 1, 2
• Inadequate PPI dosing significantly reduces treatment efficacy—always use high-dose (twice daily) PPI 1, 2
• Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates exceeding 15-20% 3
• Avoid standard triple therapy (PPI + clarithromycin + amoxicillin) as first-line treatment in areas with clarithromycin resistance >15%, which includes most of North America and Europe 2, 3
• Patient factors affecting success: Smoking increases eradication failure risk (OR 1.95), high BMI reduces drug concentrations at gastric mucosa, and poor compliance (>10% of patients) significantly reduces eradication rates 3

Adjunctive Treatment

• Probiotics can be used to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients) and improve compliance, though evidence for increasing eradication rates is limited 2, 3, 5