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 proton pump inhibitor (PPI) twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2, 3

This recommendation is based on:

• Rising global clarithromycin resistance rates (now exceeding 15% in most regions), which has rendered traditional triple therapy unacceptably ineffective 2, 3
• Bismuth quadruple therapy achieves eradication rates of 80-90% even against metronidazole-resistant strains due to the synergistic effect of bismuth with other antibiotics 2
• Bacterial resistance to bismuth is extremely rare, making this regimen effective even when other antibiotics have failed 1, 2, 3
• This approach 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 2

Specific Dosing for Bismuth Quadruple Therapy

The regimen consists of: 1, 3

• PPI (high-dose): Esomeprazole 40 mg or rabeprazole 40 mg twice daily
• Bismuth subsalicylate: 525 mg four times daily
• Metronidazole: 500 mg three to four times daily (or 250 mg four times daily)
• Tetracycline HCl: 500 mg four times daily
• Duration: 14 days (not 10 days—the full 14 days improves eradication by approximately 5%) 4, 1, 3

Alternative First-Line Option When Bismuth is Unavailable

If bismuth is not available, concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative, consisting of: 2, 3

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

Important caveat: This regimen should only be used in areas where clarithromycin resistance is <15%, which is increasingly rare in North America 2, 3

Triple Therapy: When It May Be Considered

Triple therapy (PPI + clarithromycin + amoxicillin) should generally be abandoned due to global clarithromycin resistance exceeding 15% in most regions. 4, 2, 3

However, if local resistance data confirms clarithromycin resistance <15%, the regimen would be: 4, 3

• PPI (high-dose) twice daily
• Clarithromycin 500 mg twice daily
• Amoxicillin 1000 mg twice daily
• Duration: 14 days (extending from 7 to 14 days improves eradication by approximately 5%) 4, 3

Critical Optimization Strategies

PPI Dosing is Crucial

• Always use high-dose PPI twice daily (not standard dose)—this increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity 1, 3
• Esomeprazole 40 mg or rabeprazole 40 mg twice daily are preferred over lower potency PPIs 4
• Confirm patients are taking the PPI correctly (30-60 minutes before meals) to maximize absorption 1

Treatment Duration Matters

• 14 days is superior to 7-10 days for all regimens, improving eradication success by approximately 5% 4, 1, 3

Adjunctive Probiotics

• Consider probiotics to reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve compliance 2, 5

Second-Line Treatment After First-Line Failure

After failure of clarithromycin-containing first-line therapy, use bismuth quadruple therapy (if not previously used) or levofloxacin-containing triple therapy. 4, 1, 3

Levofloxacin-Based Triple Therapy

The regimen consists of: 3

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

Critical caveat: Rising levofloxacin resistance rates (11-30% primary resistance, 19-30% secondary resistance) should be considered—do not use if the patient has had prior fluoroquinolone exposure 4, 2

Third-Line and Rescue Therapy

After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 2, 3

If susceptibility testing is unavailable: 1, 2

• Rifabutin-based triple therapy is highly effective: PPI twice daily + amoxicillin 1000 mg twice daily + rifabutin 150 mg twice daily for 14 days
• Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections 1, 2
• High-dose dual therapy: PPI (very high dose) + amoxicillin 1000 mg three times daily for 14 days 2

Key Principle for Rescue Therapy

Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance is likely 1, 2, 3

Special Dosing Considerations

H. pylori-Specific Dosing from FDA Label

For triple therapy with clarithromycin and lansoprazole: 6

• Amoxicillin 1000 mg + clarithromycin 500 mg + lansoprazole 30 mg, all given twice daily for 14 days

Renal Impairment

For patients with severe renal impairment (GFR <30 mL/min): 6

• Reduce amoxicillin to 500 mg or 250 mg every 12 hours (GFR 10-30 mL/min)
• For GFR <10 mL/min: 500 mg or 250 mg every 24 hours
• Hemodialysis patients: Administer additional dose during and at end of dialysis

Penicillin Allergy

• In bismuth quadruple therapy, tetracycline can substitute for amoxicillin 3
• Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 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, 3

Never use serology to confirm eradication—antibodies persist long after successful treatment 1, 3

Common Pitfalls to Avoid

Inadequate PPI Dosing

• The single most common correctable error is using standard-dose PPI once daily instead of high-dose twice daily 1, 3
• This significantly reduces treatment efficacy by 6-10% 1

Repeating Failed Antibiotics

• Clarithromycin resistance develops after exposure—never reuse it after first-line failure 1, 2, 3
• Levofloxacin resistance develops rapidly—avoid empiric use if prior fluoroquinolone exposure 4, 2

Insufficient Treatment Duration

• 7-day regimens are inadequate—always use 14 days 4, 1, 3

Assuming High Clarithromycin Susceptibility

• Clarithromycin resistance now exceeds 15% in most North American regions, making traditional triple therapy first-line unacceptable 2, 3
• The WHO has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotics due to high clarithromycin resistance 2

Medication Timing

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 6
• PPIs should be taken 30-60 minutes before meals for optimal acid suppression 1