H. pylori Treatment
First-Line Treatment Recommendation
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate (262 mg, 2 tablets four times daily), metronidazole (500 mg three to four times daily), and tetracycline HCl (500 mg four times daily). 1, 2
This regimen achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, and bacterial resistance to bismuth is essentially nonexistent. 1, 2
Critical Optimization Factors
Use high-dose PPI twice daily (preferably esomeprazole or rabeprazole 40 mg), taken 30 minutes before meals on an empty stomach, which increases cure rates by 8-12% compared to standard dosing. 1
14-day treatment duration is mandatory, improving eradication by approximately 5% compared to 7-10 day regimens. 1, 2
Avoid doxycycline despite being a tetracycline derivative—it is ineffective for H. pylori and specifically excluded from treatment regimens. Use only tetracycline HCl. 3
Alternative First-Line Regimen (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily. 1, 2
This regimen should only be used when bismuth is unavailable and in areas where clarithromycin resistance is <15%. 1
Second-Line Treatment After First-Line Failure
After bismuth quadruple therapy failure, use levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure): PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily). 1, 4, 2
This achieves approximately 74-75% eradication rates after non-bismuth quadruple therapy failure. 4
Critical caveat: Never use levofloxacin if the patient has prior fluoroquinolone exposure for any indication, as resistance develops rapidly. 1
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 5, 2
Rifabutin triple therapy for 14 days: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily. This is highly effective as rescue therapy because rifabutin resistance is rare. 1, 2
High-dose dual amoxicillin-PPI therapy for 14 days: amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily. This is an alternative when other options are exhausted. 1
FDA-Approved Regimens for H. pylori
Triple therapy: amoxicillin 1 gram + clarithromycin 500 mg + lansoprazole 30 mg, all given twice daily for 14 days. 6
Dual therapy: amoxicillin 1 gram + lansoprazole 30 mg, each given three times daily for 14 days (for patients allergic or intolerant to clarithromycin). 6
Key Antibiotics That Can Be Re-Used
Amoxicillin and tetracycline can be re-used because resistance remains extremely rare (<5%). 1
Metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes in vitro resistance. 1
Never re-use clarithromycin or levofloxacin after prior exposure—resistance develops rapidly and is universal within the macrolide family. 1
Common Pitfalls to Avoid
Never assume low clarithromycin resistance without local surveillance data—most regions in North America now have resistance rates >15-20%, making traditional triple therapy unacceptably ineffective. 1
Standard-dose PPI once daily is inadequate—always use twice-daily dosing to maximize gastric pH elevation. 1
Never use serology to confirm eradication—antibodies persist long after successful treatment. Use urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1
Diarrhea occurs in 21-41% of patients during the first week due to gut microbiota disruption. Consider adjunctive probiotics to reduce this risk and improve compliance. 1, 5
Patient Factors Affecting Success
Smoking increases eradication failure risk (odds ratio 1.95). 1
High BMI, especially obesity, increases failure risk due to lower drug concentrations at the gastric mucosal level. 1
Poor compliance affects >10% of patients—address this proactively with patient education about the importance of completing the full 14-day course. 1
Special Populations
Penicillin allergy: Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains rare. 1
Renal impairment: Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose. For GFR 10-30 mL/min, use 500 mg or 250 mg every 12 hours; for GFR <10 mL/min, use 500 mg or 250 mg every 24 hours. 6