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

Treatment for H. pylori Infection

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it superior to traditional triple therapy. 1, 2

Specific Dosing Protocol:

• High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily - taken 30 minutes before meals on an empty stomach 1
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 1
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 2
• Tetracycline 500 mg four times daily 1, 2
• Duration: 14 days mandatory - this improves eradication by approximately 5% compared to shorter regimens 1, 2

Why Bismuth Quadruple Therapy is Preferred:

• Bacterial resistance to bismuth is extremely rare 1, 2
• Effective even against strains with dual resistance to clarithromycin and metronidazole 1
• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates 1
• Uses antibiotics from the WHO "Access group" (tetracycline, metronidazole) rather than "Watch group" (clarithromycin, levofloxacin), supporting antimicrobial stewardship 1

Alternative First-Line Option (When Bismuth is Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available. 1, 2

Regimen:

• PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Amoxicillin 1000 mg twice daily 1, 3
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1
• Duration: 14 days 1

This regimen should only be used in areas with documented clarithromycin resistance below 15%, and even then, bismuth quadruple therapy remains superior. 1

Second-Line Treatment After First-Line Failure

After failure of first-line therapy, bismuth quadruple therapy (if not previously used) for 14 days is the preferred second-line option. 1, 2

Alternative Second-Line: Levofloxacin Triple Therapy

If the patient has no prior fluoroquinolone exposure and is from an area with low levofloxacin resistance, use: 1, 4, 5

• PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Amoxicillin 1000 mg twice daily 1, 5
• Levofloxacin 500 mg once daily 1, 5
• Duration: 14 days 1

Critical Pitfall to Avoid:

Never repeat clarithromycin if it was in the failed regimen - resistance develops rapidly after exposure, with eradication rates dropping from 90% to 20% with resistant strains. 1

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 2, 4

Rifabutin Triple Therapy (Third-Line):

• Rifabutin 150 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Duration: 14 days 1

Rifabutin resistance is extremely rare, making this an effective rescue option after multiple failures. 1

High-Dose Dual Therapy (Alternative Rescue):

• Amoxicillin 2-3 grams daily in 3-4 split doses 1
• High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Duration: 14 days 1

Special Populations

Patients with 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 most patients who report penicillin allergy are found not to have a true allergy. 1

Critical Optimization Factors

PPI Selection and Dosing:

Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs and standard doses. 1, 2

Standard-dose PPI once daily is inadequate - always use twice-daily dosing taken 30 minutes before meals on an empty stomach, without concomitant antacids. 1

Treatment Duration:

14 days is mandatory for all regimens - extending from 7 to 14 days improves eradication success by approximately 5%. 1, 2

Patient Factors Affecting Success:

• Smoking increases risk of eradication failure (odds ratio 1.95) 1, 6
• High BMI leads to lower drug concentrations at the gastric mucosal level 1
• Poor compliance (>10% of patients) significantly reduces eradication rates 1

Confirmation of Eradication

Test for eradication success at least 4 weeks after completion of therapy using urea breath test or validated monoclonal stool antigen test. 1, 2

Discontinue PPI at least 2 weeks before testing. 1, 2

Never use serology to confirm eradication - antibodies may persist long after successful treatment. 1

Common Pitfalls to Avoid

• Never use levofloxacin as first-line therapy - this accelerates resistance development and eliminates a valuable rescue option 1
• Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin 1, 2
• Do not assume low clarithromycin resistance without local surveillance data - most regions now have high resistance rates 1
• Avoid concomitant, sequential, or hybrid therapies - they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1

Managing Treatment Side Effects

Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota. 1

Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance, though evidence for increasing eradication rates is limited. 1, 2