Treatment of H. pylori Detected in Stool
Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection detected by stool antigen testing, consisting of a high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1
First-Line Treatment Regimen
Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it the preferred initial approach. 1, 2
Specific Dosing Protocol
- Proton pump inhibitor: Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs as they increase cure rates by 8-12%) 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
- Tetracycline: 500 mg four times daily 1
- Duration: 14 days mandatory (improves eradication by approximately 5% compared to shorter regimens) 1, 2
Critical Administration Details
- Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1
- All medications should be taken at the start of meals to minimize gastrointestinal intolerance 3
Alternative First-Line Option (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available. 1
- PPI: Esomeprazole or rabeprazole 40 mg twice daily 1
- Amoxicillin: 1000 mg twice daily 1
- Clarithromycin: 500 mg twice daily 1
- Metronidazole: 500 mg twice daily 1
This regimen should only be used in areas with documented clarithromycin resistance below 15%, as resistance now exceeds 20% in most of North America and Europe. 1, 2
Second-Line Treatment After First-Line Failure
After bismuth quadruple therapy failure, levofloxacin-based triple therapy for 14 days is recommended if the patient has no prior fluoroquinolone exposure. 1, 4
- 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
Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 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
High-Dose Dual Therapy (Alternative Rescue)
- Amoxicillin: 2-3 grams daily in 3-4 split doses 1
- PPI: Double standard dose twice daily 1
- Duration: 14 days 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. 4
- Discontinue PPI at least 2 weeks before testing 4
- Never use serology to confirm eradication—antibodies persist long after successful treatment 1
Special Populations
Penicillin Allergy
Bismuth quadruple therapy is the first choice in patients with penicillin allergy, as it contains tetracycline, not amoxicillin. 1
- Consider penicillin allergy testing to enable amoxicillin use, as most patients who report allergy are found not to have true allergy 1
Prior Antibiotic Exposure
Review all prior antibiotic exposures thoroughly—avoid clarithromycin if the patient has received any macrolide (azithromycin, erythromycin) for any indication, as cross-resistance is universal. 1, 4
Avoid levofloxacin in patients with chronic lung disease or other conditions where they may have received prior fluoroquinolone exposure. 1
Critical Optimization Factors
High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate and significantly reduces treatment efficacy. 1, 2
Treatment duration of 14 days is superior to 7-10 day regimens across all treatment protocols. 1, 2
Bismuth has no described bacterial resistance, making bismuth quadruple therapy effective even against strains with dual resistance to clarithromycin and metronidazole. 1
Common Pitfalls to Avoid
Do not use clarithromycin-based triple therapy without susceptibility testing in areas where clarithromycin resistance exceeds 15-20%, which now includes most of North America and Europe. 1, 2
Do not use levofloxacin empirically as first-line therapy—this accelerates resistance development and eliminates a valuable rescue option. 1
Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1
Avoid concomitant, sequential, or hybrid therapies as they include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit. 1