What is the recommended treatment regimen for a patient with a confirmed diagnosis of H pylori (Helicobacter pylori) infection?

H. pylori Treatment Recommendations

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth 300mg four times daily, metronidazole 500mg three times daily, and tetracycline 500mg four times daily. 1

First-Line Treatment Regimen

The American Gastroenterological Association endorses bismuth quadruple therapy as the optimal first-line approach because it achieves 80-90% eradication rates even in regions with high clarithromycin and metronidazole resistance. 1, 2 This superiority stems from the fact that bacteria do not develop resistance to bismuth, and tetracycline resistance remains rare (<5%). 1

Specific dosing components:

• PPI: Twice daily dosing is mandatory—choose pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, or rabeprazole 20mg, taken 30 minutes before meals on an empty stomach. 1
• Bismuth: 300mg four times daily (bismuth subsalicylate 262mg or bismuth subcitrate 120mg). 1
• Metronidazole: 500mg three to four times daily (total 1.5-2g daily). 1
• Tetracycline: 500mg four times daily. 1
• Duration: 14 days—this improves eradication rates by approximately 5% compared to 7-10 day regimens. 1, 2

Alternative First-Line Option

If bismuth is unavailable, concomitant non-bismuth quadruple therapy is acceptable: PPI twice daily + amoxicillin 1000mg twice daily + clarithromycin 500mg twice daily + metronidazole 500mg twice daily for 14 days. 2 However, this should only be used in areas with documented clarithromycin resistance <15%. 3

Second-Line Treatment After First Failure

If clarithromycin-based therapy fails first: Use bismuth quadruple therapy as described above. 1

If bismuth quadruple therapy fails first: Switch to levofloxacin triple therapy consisting of PPI twice daily + amoxicillin 1000mg twice daily + levofloxacin 500mg once daily (or 250mg twice daily) for 14 days. 1, 4 This assumes no prior fluoroquinolone exposure, as resistance develops rapidly. 3

Third-Line and Rescue Therapies

After two failed treatment attempts, antibiotic susceptibility testing should be obtained before proceeding. 1, 3 Molecular testing for clarithromycin and levofloxacin resistance can guide earlier therapy selection. 1

Rifabutin triple therapy is highly effective as third-line treatment: PPI twice daily + amoxicillin 1000mg twice daily + rifabutin 150mg twice daily (or 300mg once daily) for 14 days. 1, 2

High-dose dual therapy serves as a rescue option when other regimens are exhausted: amoxicillin 2-3 grams daily in 3-4 divided doses + high-dose PPI twice daily for 14 days. 1, 2

Critical Optimization Factors

PPI dosing is the most common pitfall: High-dose PPI twice daily increases eradication efficacy by 6-10% compared to once-daily dosing. 2, 3 Always take 30 minutes before meals on an empty stomach, and avoid concomitant use of other antacids. 1, 3

Antibiotic reuse rules:

• Never reuse: Clarithromycin and levofloxacin (high resistance rates after single exposure). 1
• Safe to reuse: Amoxicillin and tetracycline (low resistance rates). 1

Special Populations

Penicillin allergy: Bismuth quadruple therapy is the first choice since it contains tetracycline instead of amoxicillin. 1, 2 Consider penicillin allergy testing to delist the allergy and enable amoxicillin use. 1

If penicillin allergy is confirmed and bismuth is unavailable, use PPI + clarithromycin + metronidazole for 14 days, but only in areas with documented clarithromycin resistance <15%. 1

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after stopping PPIs. 1, 2, 3 Serology is unreliable for confirmation and should not be used. 3

Common Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data—avoid repeating clarithromycin if the patient has any prior macrolide exposure for any indication. 3
• Do not reduce bismuth dosing below 300mg four times daily—this represents the evidence-based standard, and dose reduction is not supported by guidelines. 3
• Avoid sequential therapy—concomitant quadruple therapy is superior. 3
• Do not use levofloxacin empirically as first-line due to rapidly rising fluoroquinolone resistance rates. 3