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 PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment Options

Preferred Regimen: Bismuth Quadruple Therapy

• Bismuth quadruple therapy for 14 days is the most effective first-line option due to increasing global clarithromycin resistance and rare bacterial resistance to bismuth. 1, 2
• The regimen consists of: 1, 2
  • High-dose PPI (e.g., esomeprazole 40 mg or rabeprazole 40 mg) twice daily
  • Bismuth subsalicylate
  • Metronidazole
  • Tetracycline HCl
• High-dose PPI (twice daily) is crucial as it increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity. 1, 2
• The 14-day duration is preferred over 7-10 days, improving eradication success by approximately 5%. 3, 2

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy

• When bismuth is unavailable, use concomitant therapy consisting of PPI twice daily, clarithromycin 500 mg twice daily, amoxicillin 1000 mg twice daily, and metronidazole 500 mg twice daily for 14 days. 2, 4
• This regimen should only be used in areas with clarithromycin resistance <15%. 2

Traditional Triple Therapy (Restricted Use)

• PPI-clarithromycin-amoxicillin triple therapy for 14 days may be considered only in areas with documented clarithromycin resistance <15%. 3, 2
• Standard triple therapy should be abandoned when clarithromycin resistance exceeds 15-20% due to unacceptably low eradication rates. 2, 4
• The FDA-approved triple therapy regimen is: amoxicillin 1 gram, clarithromycin 500 mg, and lansoprazole 30 mg, all given twice daily for 14 days. 5

Second-Line Treatment After First-Line Failure

After Clarithromycin-Containing Therapy Fails

• Use bismuth quadruple therapy (if not previously used) or levofloxacin-containing triple therapy. 3, 1
• Levofloxacin triple therapy consists of: PPI twice daily, amoxicillin 1000 mg twice daily, and levofloxacin 500 mg once daily (or 250 mg twice daily) for 14 days. 2
• Rising rates of levofloxacin resistance must be considered when selecting this option. 3, 1

After Bismuth Quadruple Therapy Fails

• Levofloxacin-containing triple therapy is recommended in areas with low levofloxacin resistance. 3

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

• Antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 2
• When susceptibility testing is unavailable, avoid previously used antibiotics, especially clarithromycin and levofloxacin. 1, 4

Rifabutin-Based Therapy

• Rifabutin triple therapy (PPI, amoxicillin, rifabutin) for 14 days is effective for persistent infection after multiple failures. 1, 4
• Rifabutin has the advantage of rare bacterial resistance, making it valuable for refractory cases. 1
• Reserve rifabutin for patients who have failed at least 3 prior treatment options to preserve this antibiotic. 4

Critical Optimization Strategies

PPI Administration

• Always use high-dose PPI (twice daily) rather than standard dosing. 1, 2
• Confirm patients take PPI correctly to maximize absorption and activation. 1
• Take all medications at the start of a meal to minimize gastrointestinal intolerance. 5

Treatment Duration

• All H. pylori eradication regimens should be given for 14 days, not 7-10 days. 1, 2
• Extending duration from 7 to 14 days improves eradication by approximately 5%. 3, 2

Antibiotic Selection Principles

• Never repeat antibiotics to which the patient has been previously exposed, particularly clarithromycin and levofloxacin. 1, 2
• Bismuth is valuable because bacterial resistance is extremely rare, making it effective even against metronidazole-resistant strains. 1, 2

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 as antibodies persist long after successful treatment. 1, 2

Common Pitfalls and Caveats

Antibiotic Resistance Patterns

• Clarithromycin resistance has increased globally from 9% (1998) to 17.6% (2008-2009), making traditional triple therapy less effective. 2, 4
• Metronidazole resistance has limited effect on bismuth quadruple therapy outcomes when adequate dosages and durations are used. 3
• Levofloxacin resistance rates range from 11-30% (primary) and 19-30% (secondary). 4

Dosing Errors

• Inadequate PPI dosing significantly reduces treatment efficacy; standard-dose PPI is insufficient. 1, 2
• In patients with high BMI, especially obese individuals, higher drug concentrations may be needed due to increased distribution volume. 3

Special Populations

• In penicillin-allergic patients, amoxicillin can be replaced with tetracycline in appropriate regimens. 2
• For renal impairment (GFR <30 mL/min), adjust amoxicillin dosing and avoid the 875 mg dose. 5
• In children, avoid fluoroquinolones and tetracyclines, limiting treatment options. 2

Adjunctive Therapy

• Consider probiotics to reduce antibiotic-associated diarrhea and improve compliance, though evidence for increased eradication rates is limited. 2, 6
• Smoking is a risk factor for treatment failure, with an odds ratio of 1.95 for eradication failure. 3