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

H. pylori Treatment and Dosage

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth subsalicylate ~300 mg four times daily, metronidazole 500 mg three times daily, and tetracycline 500 mg four times daily. 1, 2, 3

First-Line Treatment: Bismuth Quadruple Therapy

The American Gastroenterological Association endorses this regimen as the optimal first-line approach, achieving 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effects. 1

Specific dosing components:

• PPI (twice daily): Omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, esomeprazole 20-40 mg, or rabeprazole 20-40 mg 2, 3
  • Esomeprazole or rabeprazole are preferred over pantoprazole, as they increase cure rates by an additional 8-12% 1
  • Must be taken 30 minutes before meals on an empty stomach 2
• Bismuth subsalicylate: ~300 mg four times daily 1, 3
• Metronidazole: 500 mg three times daily (total 1.5 g/day) 1, 2, 3
  • Take with food to minimize GI side effects 2
  • Patients must avoid alcohol due to disulfiram-like reactions 2
• Tetracycline: 500 mg four times daily 1, 3
• Duration: 14 days is mandatory—this achieves 93-97% eradication versus only 80-82% with 7-10 day regimens 1, 3

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy

Use only in regions with documented clarithromycin resistance <15%: 1

• PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily + metronidazole 500 mg twice daily for 14 days 1, 2
• Clarithromycin-based triple therapy should be avoided in areas with ≥15% resistance, as resistance develops rapidly after any macrolide exposure 1

Second-Line Treatment (After First-Line Failure)

If clarithromycin-based therapy fails: Use bismuth quadruple therapy as described above 3

If bismuth quadruple therapy fails: Levofloxacin triple therapy 3

• PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) for 14 days 3
• Critical caveat: Never use levofloxacin empirically as first-line due to rapidly rising fluoroquinolone resistance 1

Third-Line and Rescue Therapies

After two failed treatment attempts, obtain antibiotic susceptibility testing before proceeding. 1, 3 Molecular testing for clarithromycin and levofloxacin resistance can guide earlier therapy selection. 1, 3

Rifabutin triple therapy (highly effective rescue option): 1, 3

• PPI twice daily + amoxicillin 1000 mg twice daily + rifabutin 150 mg twice daily (or 300 mg once daily) for 10-14 days 1, 3

High-dose dual therapy (alternative rescue): 3

• Amoxicillin 2-3 grams daily in 3-4 divided doses + high-dose PPI twice daily 3

Critical Optimization Factors

High-dose PPI twice daily is non-negotiable: This increases eradication efficacy by 6-10% compared to standard once-daily dosing. 1 Always administer 30 minutes before meals on an empty stomach. 2, 3

Antibiotic reuse rules: 3

• Never reuse: Clarithromycin or levofloxacin (high resistance rates) 3
• Can reuse: Amoxicillin and tetracycline (low resistance rates) 3

Special Populations

Penicillin allergy: Bismuth quadruple therapy is the first choice, as it contains tetracycline instead of amoxicillin. 3

Severe renal impairment (GFR <30 mL/min): 4

• GFR 10-30 mL/min: Amoxicillin 500 mg or 250 mg every 12 hours 4
• GFR <10 mL/min: Amoxicillin 500 mg or 250 mg every 24 hours 4
• Hemodialysis: Additional dose during and at end of dialysis 4

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after stopping PPIs. 1, 3 Serology is unreliable for confirmation and should never be used. 1, 3

Common Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data 1
• Avoid repeating clarithromycin if the patient has any prior macrolide exposure for any indication 1
• Do not reduce bismuth dosing below ~300 mg four times daily—this represents the evidence-based standard, and dose reduction is not supported by any guideline 1
• Do not shorten treatment duration below 14 days—this consistently reduces eradication rates by approximately 5% 1, 3
• Avoid concomitant use of other antacids with PPIs during treatment 1

Adjunctive Therapies

Probiotics can reduce antibiotic-associated diarrhea and improve compliance, but their benefit for improving eradication rates remains unproven. 1