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

H. pylori Infection Treatment

First-Line Treatment Recommendation

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

This recommendation is based on:

• Eradication rates of 80-90% even in areas with high clarithromycin and metronidazole resistance 1
• No bacterial resistance to bismuth has been described, making this regimen highly reliable 1
• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective with eradication rates dropping to approximately 20% with resistant strains 1

Critical Optimization Factors

PPI Dosing

• Use high-dose PPI twice daily (not standard once-daily dosing), which increases cure rates by 6-12% 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily may provide an additional 8-12% improvement in eradication rates 1
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1

Treatment Duration

• 14 days is mandatory and improves eradication success by approximately 5% compared to 7-10 day regimens 1, 2

Medication Timing

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 3

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 1

• This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment 1
• Only use in areas with clarithromycin resistance <15%, which is now rare in most regions 1, 2

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Was NOT Used First-Line:

• Bismuth quadruple therapy for 14 days 1, 4

If Bismuth Quadruple Therapy Failed or Was Used First-Line:

• Levofloxacin triple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 4, 2
• Critical caveat: Do not use if patient has prior fluoroquinolone exposure for any indication, as resistance rates are rising (11-30% primary, 19-30% secondary) 1

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts:

• Antibiotic susceptibility testing should guide further treatment whenever possible 1, 4, 2

Rescue Options (in order of preference):

1. Rifabutin triple therapy for 14 days: Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily 1, 4

   • Rifabutin resistance is extremely rare 1
   • Highly effective after multiple treatment failures 1

2. 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

   • Amoxicillin resistance remains rare (<5%) 1

Special Populations

Penicillin Allergy:

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1
• Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as many reported allergies are not true allergies 1

Renal Impairment:

• GFR 10-30 mL/min: Amoxicillin 500 mg or 250 mg every 12 hours 3
• GFR <10 mL/min: Amoxicillin 500 mg or 250 mg every 24 hours 3
• Hemodialysis: Administer additional dose during and at end of dialysis 3

Verification of Eradication

• Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy 1, 4, 2
• Discontinue PPI at least 2 weeks before testing 1, 2
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1, 4

Critical Pitfalls to Avoid

Antibiotic Selection Errors:

• Never repeat clarithromycin or levofloxacin if previously used, as resistance develops rapidly after exposure 1, 4
• Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1
• Avoid using levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance 1

Dosing Errors:

• Standard-dose PPI once daily is inadequate—always use twice-daily dosing 1
• Do not use 7-day regimens—they are inferior to 14-day treatment 1, 2

Patient Factors Affecting Success:

• Smoking increases eradication failure risk (odds ratio 1.95) 1
• High BMI/obesity increases failure risk due to lower drug concentrations at gastric mucosal level 1
• Poor compliance accounts for >10% of failures—address this proactively 1

Adjunctive Measures

• Consider probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients during first week) and improve compliance 1
• Probiotics do not significantly increase eradication rates but may reduce side effects 1, 5