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

H. pylori Treatment Regimen

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, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1

First-Line Treatment: Bismuth Quadruple Therapy

The standard regimen consists of: 1, 2

• PPI (high-dose) twice daily - taken 30 minutes before meals on an empty stomach 1, 2
  • Preferred agents: Esomeprazole 40mg or rabeprazole 40mg twice daily (increases cure rates by 8-12% compared to standard PPIs) 1
  • Standard alternatives: Omeprazole 20mg, lansoprazole 30mg, or pantoprazole 40mg twice daily 2
• Bismuth subsalicylate 262mg or bismuth subcitrate 120mg four times daily 3
• Metronidazole 500mg three times daily (total 1.5g/day) 1, 2
  • Take with food to minimize GI side effects 2
  • Patients must avoid alcohol during treatment (disulfiram-like reaction risk) 2
• Tetracycline 500mg four times daily 1, 3

Duration: 14 days is mandatory - this improves eradication success by approximately 5% compared to 7-10 day regimens 1, 3

Why Bismuth Quadruple Therapy is Preferred

• Effective even against clarithromycin-resistant and metronidazole-resistant strains due to bismuth's synergistic effect 1, 3
• No bacterial resistance to bismuth has been described 3
• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 3
• Uses antibiotics from the WHO "Access group" (tetracycline, metronidazole) rather than "Watch group" (clarithromycin, levofloxacin), supporting antimicrobial stewardship 3

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy

Use only when bismuth is unavailable: 1, 3

• PPI twice daily (high-dose preferred)
• Amoxicillin 1000mg twice daily 4
• Clarithromycin 500mg twice daily
• Metronidazole 500mg twice daily
• Duration: 14 days 1

Critical caveat: This regimen should only be used in areas with documented clarithromycin resistance <15%, which is now rare in most regions 1, 3

Second-Line Treatment (After First-Line Failure)

Option 1: Bismuth Quadruple Therapy

If not used as first-line, use the same regimen described above for 14 days 1, 3

Option 2: Levofloxacin Triple Therapy

Use only in areas with low levofloxacin resistance (<15%): 1, 3

• PPI twice daily (high-dose)
• Amoxicillin 1000mg twice daily
• Levofloxacin 500mg once daily OR 250mg twice daily
• Duration: 14 days 1

Important warning: Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary resistance) 1, 3

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible - this is the current standard recommendation 1, 3

Rifabutin-Based Triple Therapy (Highly Effective Rescue Option)

• Rifabutin 150mg twice daily
• Amoxicillin 1000mg twice daily
• PPI twice daily (high-dose)
• Duration: 14 days 1, 3

Key advantage: Rifabutin resistance is extremely rare, making this highly effective after multiple treatment failures 1, 3

High-Dose Dual Therapy (Alternative Rescue)

• Amoxicillin 2-3 grams daily in 3-4 divided doses
• PPI twice daily (high-dose)
• Duration: 14 days 3

Critical Optimization Factors

PPI Dosing is Mandatory for Success

• High-dose PPI twice daily increases eradication efficacy by 6-10% compared to standard once-daily dosing 1, 3
• Must be taken 30 minutes before meals on an empty stomach 1, 2
• Do not use concomitant antacids with PPIs during treatment 1

Treatment Duration

• 14 days is superior to 7-10 day regimens by approximately 5% 1, 3

Antibiotic Selection Principles

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin where resistance develops rapidly after exposure 1, 3
• Avoid clarithromycin if patient has prior macrolide exposure for any indication (cross-resistance is universal) 3
• Metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes in vitro resistance 3
• Amoxicillin and tetracycline can be re-used because resistance remains rare (1-5%) 1, 3

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test: 1, 3

• At least 4 weeks after completion of therapy
• At least 2 weeks after PPI discontinuation
• Never use serology to confirm eradication - antibodies persist long after successful treatment 3

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 3

Adjunctive Therapies

Probiotics can be used to reduce antibiotic-associated diarrhea and improve patient compliance, but are of unproven benefit for improving eradication rates 1, 3

Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota 3

Common Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data - most regions now have resistance >15% 1, 3
• Do not use standard-dose PPI once daily - always use twice-daily high-dose dosing 3
• Do not use sequential therapy - it allows resistance to develop during treatment 1
• Ensure patient compliance - more than 10% of patients are poor compliers, leading to much lower eradication rates 3
• Address smoking cessation - smoking increases eradication failure risk (OR 1.95) 3
• Consider that high BMI increases failure risk due to lower drug concentrations at gastric mucosal level 3