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, achieving 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1, 2, 3

First-Line Treatment Regimen

Bismuth quadruple therapy consists of:

• High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, as they increase cure rates by 8-12% compared to other PPIs) 1, 3
• 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, 3
• Tetracycline 500 mg four times daily 1, 3
• Duration: 14 days mandatory (improves eradication by ~5% compared to shorter regimens) 1, 2, 3

Why bismuth quadruple therapy is superior:

• No bacterial resistance to bismuth has been described 1
• Bismuth's synergistic effect overcomes metronidazole resistance even when present 1
• Effective against clarithromycin-resistant strains (which now exceed 15-20% in most of North America and Europe) 1
• Tetracycline resistance remains rare (<5%) 1

Critical administration details:

• Take PPI 30 minutes before meals on an empty stomach 1
• Avoid concomitant use of other antacids 1

Alternative First-Line Option (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days: 1, 2

• High-dose PPI twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1

This regimen achieves 80-90% eradication rates but should only be used when bismuth is unavailable, as it includes clarithromycin (to which resistance is increasing globally). 1, 2

Second-Line Treatment (After First-Line Failure)

Levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure): 1, 3

• High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Levofloxacin 500 mg once daily (or 250 mg twice daily) 1

Important caveat: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary resistance), so avoid if patient has had any prior fluoroquinolone exposure for any indication. 1

Alternative second-line option:

• Use bismuth quadruple therapy if not used as first-line 1, 2

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 2, 3

Rifabutin triple therapy for 14 days (reserved for multiple failures): 1

• Rifabutin 150 mg twice daily 1
• Amoxicillin 1000 mg twice daily 1
• High-dose PPI twice daily 1

High-dose dual amoxicillin-PPI therapy for 14 days (alternative rescue option): 1

• Amoxicillin 2-3 grams daily in 3-4 split doses 1
• High-dose PPI (double standard dose) twice daily 1

Critical Optimization Factors

Never repeat antibiotics that failed previously:

• Especially avoid re-using clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2
• Amoxicillin, tetracycline, and bismuth can be re-used because resistance remains rare 1

Patient factors affecting success:

• Smoking increases eradication failure risk (OR 1.95) 1, 3
• High BMI reduces drug concentrations at gastric mucosal level 1, 3
• Poor compliance occurs in >10% of patients and significantly reduces efficacy 1, 3

Managing Side Effects

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

Consider adjunctive probiotics to reduce antibiotic-associated diarrhea and improve compliance, though they have no solid evidence to increase eradication rates. 1, 3

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using: 1, 2

• Urea breath test, OR 1
• Validated monoclonal stool antigen test 1

Critical testing requirements:

• Discontinue PPI at least 2 weeks before testing 1
• Never use serology to confirm eradication (antibodies persist long after successful treatment) 1

Special Populations

For patients with penicillin allergy:

• Bismuth quadruple therapy is the first choice (contains tetracycline, not amoxicillin) 1
• Consider penicillin allergy testing to enable amoxicillin use, as most patients with reported allergy are not truly allergic 1

For patients with prior clarithromycin exposure (for any indication):

• Avoid clarithromycin-containing regimens due to universal cross-resistance within the macrolide family 1

Common Pitfalls to Avoid

• Never use standard-dose PPI once daily (inadequate acid suppression; always use twice-daily dosing) 1
• Never use 7-day regimens (14 days is mandatory for optimal efficacy) 1, 2, 3
• Never use levofloxacin as first-line therapy (accelerates resistance development and eliminates valuable rescue option) 1
• Never assume low clarithromycin resistance without local surveillance data (most regions now have >15-20% resistance) 1