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

Treatment for H. Pylori

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate 524 mg four times daily, metronidazole, and tetracycline. 1, 2

First-Line Treatment Regimen

Bismuth Quadruple Therapy (Preferred):

• PPI twice daily + bismuth subsalicylate 524 mg four times daily + metronidazole + tetracycline for 14 days 1, 2
• This regimen achieves eradication rates of 80-90% even against metronidazole-resistant strains 1
• Bacterial resistance to bismuth is extremely rare, making this highly effective 1, 2
• Uses antibiotics from the WHO "Access group" (tetracycline, metronidazole) rather than "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 1

Alternative First-Line (When Bismuth Unavailable):

• Concomitant non-bismuth quadruple therapy: PPI twice daily + amoxicillin 1000 mg twice daily + metronidazole 500 mg twice daily + clarithromycin 500 mg twice daily for 14 days 1
• Only use in areas with clarithromycin resistance <15% 1

Why Bismuth Quadruple Therapy is Preferred

• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 1
• The WHO has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotics due to high clarithromycin resistance rates 1
• Standard triple therapy should be abandoned when clarithromycin resistance exceeds 15-20% 1

Treatment Optimization Strategies

Duration:

• Always treat for 14 days to maximize eradication rates 1, 2
• Extending from 7 to 14 days improves success by approximately 5% 1

PPI Dosing:

• Use high-dose PPI twice daily to reduce gastric acidity and enhance antibiotic activity 1
• Higher doses of metronidazole (1.5-2 g daily in divided doses) improve eradication rates even with resistant strains when combined with bismuth 1

Antibiotic Selection:

• Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin 1, 2
• For penicillin allergy: verify the allergy—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 1

FDA-Approved H. pylori Regimens (Adult Patients)

Triple Therapy (FDA-approved):

• Amoxicillin 1 gram + clarithromycin 500 mg + lansoprazole 30 mg, all twice daily for 14 days 3
• Only use in areas with documented low clarithromycin resistance 1

Dual Therapy (FDA-approved):

• Amoxicillin 1 gram + lansoprazole 30 mg, both three times daily for 14 days 3
• Reserved for patients allergic or intolerant to clarithromycin or with known clarithromycin resistance 3

Second-Line and Rescue Therapies

After First-Line Failure:

• Levofloxacin-based triple therapy: PPI + amoxicillin + levofloxacin for 14 days (only in areas with low levofloxacin resistance and if not previously used) 1
• Rifabutin triple therapy: PPI + amoxicillin + rifabutin 150 mg twice daily for 14 days 1, 4
• Rifabutin is highly effective as rescue therapy after previous treatment failures 1

After Two Failed Attempts:

• Antibiotic susceptibility testing is mandatory to guide further treatment 1, 4
• High-dose dual amoxicillin-PPI therapy is an alternative rescue option 1

Critical Pitfalls to Avoid

• Do NOT use 7-10 day regimens—69% of European gastroenterologists still make this error 5
• Do NOT use standard triple therapy empirically where clarithromycin resistance exceeds 15% (most of North America) 1
• Do NOT use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates 1
• Do NOT repeat clarithromycin or levofloxacin after treatment failure—over 15% of clinicians still make this mistake 5
• Do NOT use low-dose PPI once daily—48% of clinicians still underdose PPIs 5

Managing Treatment Side Effects

• Diarrhea occurs in 21-41% of patients during the first week due to gut microbiota disruption 1
• Consider adjunctive probiotics to reduce diarrhea risk and improve compliance 1
• Take amoxicillin at the start of a meal to minimize gastrointestinal intolerance 3

Verification of Eradication

• Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy 1
• Wait at least 2 weeks after PPI discontinuation before testing 1
• Failure to check eradication success occurs in 6% of cases—this is unacceptable 5

Special Populations

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
• Do NOT use the 875 mg amoxicillin dose if GFR <30 mL/min 3

Pediatric Patients (≥3 months and <40 kg):

• Mild/moderate infections: 25 mg/kg/day amoxicillin in divided doses every 12 hours 3
• Severe infections: 45 mg/kg/day amoxicillin in divided doses every 12 hours 3