What is the appropriate medication regimen, including dosages and duration, for an adult with a positive Helicobacter pylori urea‑breath test?

H. pylori Treatment Regimen After Positive Breath Test

For an adult with a positive H. pylori urea breath test, the first-line treatment is bismuth quadruple therapy for 14 days: high-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily + bismuth subsalicylate 262 mg (2 tablets) four times daily + metronidazole 500 mg three to four times daily + tetracycline 500 mg four times daily. 1, 2

First-Line Therapy: Bismuth Quadruple Regimen

Medication dosages and timing:

• Proton pump inhibitor (PPI): Esomeprazole or rabeprazole 40 mg twice daily (high-dose formulation is mandatory; standard-dose PPIs reduce cure rates by 8-12%) 1
• Bismuth subsalicylate: 262 mg (2 tablets) four times daily, taken 30 minutes before meals and at bedtime 1
• Metronidazole: 500 mg three to four times daily (total daily dose 1.5-2 g), taken 30 minutes after meals 1
• Tetracycline: 500 mg four times daily (doxycycline substitution significantly lowers eradication and should not be used) 1

Duration: 14 days is mandatory—this improves eradication rates by approximately 5% compared to 7-10 day regimens 1, 2

Expected efficacy: This regimen achieves 80-90% eradication even in regions with high clarithromycin and metronidazole resistance 1, 2

Alternative First-Line Regimen (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days (only acceptable in regions where clarithromycin resistance is <15%): 1, 2

• PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily 3

Critical caveat: Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making bismuth quadruple therapy the superior choice 1

Alternative First-Line: Rifabutin Triple Therapy

For patients without penicillin allergy: 1

• Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + high-dose PPI twice daily for 14 days 1

Optimization Factors That Directly Impact Success

Medication administration:

• All medications should be taken at the start of meals to maximize absorption and minimize gastrointestinal side effects 1, 2
• PPIs must be taken twice daily (once-daily dosing markedly reduces efficacy) 1
• Complete the full 14-day course without interruption 1, 2

Patient-related factors that increase failure risk:

• Smoking approximately doubles failure risk (odds ratio 1.95) 1, 2
• High body mass index reduces gastric drug concentrations 1, 2

Confirmation of Eradication (Post-Treatment Testing)

Testing must be performed ≥4 weeks after completing therapy using: 1, 2

• Urea breath test (preferred): Sensitivity and specificity >90% for active infection 3
• Monoclonal stool antigen test (alternative): Sensitivity and specificity >90% in untreated patients 3

Critical pre-testing requirements:

• Discontinue PPIs at least 2 weeks before testing (7-14 days minimum to avoid false-negative results) 3, 1, 2
• Withhold antibiotics and bismuth for at least 4 weeks before testing 3
• Patient should fast for at least 6 hours before breath test 3

Do not use serology to confirm eradication—antibodies persist long after successful treatment and cannot distinguish active from past infection 3, 1, 2

Second-Line Therapy After First-Line Failure

If bismuth quadruple therapy fails and the patient has no prior fluoroquinolone exposure: 1, 2

• Levofloxacin triple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily 1, 2

Critical principle: Do not reuse antibiotics that have previously failed (e.g., clarithromycin, levofloxacin) because resistance develops rapidly after exposure 1

Rescue Strategies After Two Failed Eradication Attempts

After two documented failures with confirmed adherence, antibiotic susceptibility testing should guide further treatment 1

If susceptibility testing is unavailable, consider: 1

• Rifabutin triple therapy (if not previously used): Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + high-dose PPI twice daily for 14 days 1
• High-dose dual therapy: Amoxicillin 2-3 g/day divided 3-4 times daily + esomeprazole or rabeprazole 40 mg twice daily for 14 days 1

Special Populations

Penicillin allergy:

• Bismuth quadruple therapy is the preferred first-line regimen because it does not contain amoxicillin 1
• Consider allergy testing after failure, as many reported allergies are not true 1

Elderly patients:

• Age alone is not a contraindication to tetracycline 1
• Bismuth quadruple therapy remains the regimen of choice 1

Common Pitfalls to Avoid

• Using standard-dose PPIs instead of high-dose formulations (reduces cure rates by 8-12%) 1
• Prescribing once-daily PPI dosing instead of twice-daily (markedly reduces efficacy) 1
• Testing for eradication too early (<4 weeks) or without adequate PPI washout (causes false-negative results) 3, 1
• Using doxycycline instead of tetracycline (significantly lower eradication) 1
• Shortening treatment duration to <14 days (reduces success by ~5%) 1, 2
• Reusing antibiotics that previously failed (resistance is already established) 1