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 PPI twice daily, bismuth subsalicylate (~300 mg four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily), achieving 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1, 2, 3
This regimen is superior because:
- Bacterial resistance to bismuth is extremely rare 1, 2, 3
- It remains effective against metronidazole-resistant strains due to bismuth's synergistic effect 1, 2
- Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates 1, 2
Critical Optimization Factors
High-dose PPI twice daily is mandatory—use esomeprazole or rabeprazole 40 mg twice daily, taken 30 minutes before meals on an empty stomach, as this increases cure rates by 8-12% compared to standard PPIs and by 6-10% compared to once-daily dosing. 1, 2, 3
Treatment duration must be 14 days—this improves eradication success by approximately 5% compared to 7-10 day regimens. 1, 2, 3, 4
Alternative First-Line Options
When Bismuth is Unavailable
Concomitant non-bismuth quadruple therapy is the preferred alternative: PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily + metronidazole 500 mg twice daily for 14 days. 1, 2, 3 This regimen administers all antibiotics simultaneously, preventing resistance development during treatment. 1
In Areas with Documented Low Clarithromycin Resistance (<15%)
Triple therapy may be considered: PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days. 2, 3 However, never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1
Second-Line Treatment After First-Line Failure
After failure of clarithromycin-containing therapy, use bismuth quadruple therapy (if not previously used) for 14 days. 1, 3
After failure of bismuth quadruple therapy, use levofloxacin triple therapy (if no prior fluoroquinolone exposure): PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily for 14 days. 1, 2, 3
Critical Pitfall to Avoid
Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure—eradication rates drop from 90% to 20% with resistant strains. 1, 2
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, obtain antibiotic susceptibility testing to guide further treatment. 1, 2, 3, 4
Rifabutin-based triple therapy is highly effective as rescue therapy: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days. 1, 2, 3 Rifabutin resistance is rare, making this an effective option after multiple failures. 1
High-dose dual amoxicillin-PPI therapy is an alternative rescue option: amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days. 1, 2
Special Populations
Penicillin Allergy
Bismuth quadruple therapy is the first choice in patients with confirmed penicillin allergy, as it contains tetracycline, not amoxicillin. 1, 3 However, consider penicillin allergy testing to enable amoxicillin use, as most patients who report allergy are found not to have a true allergy. 1
If bismuth is unavailable: clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily + PPI twice daily for 14 days (only in areas with clarithromycin resistance <15%). 1
Verification of Eradication
Confirm eradication with 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, 2, 3 Never use serology to confirm eradication—antibodies may persist long after successful treatment. 1, 2
Common Pitfalls to Avoid
- Inadequate PPI dosing: Standard once-daily PPI is inadequate and significantly reduces treatment efficacy. 1, 3
- Avoiding concomitant antacids: Do not use other antacids with PPIs during treatment. 1
- Prior macrolide exposure: Avoid clarithromycin if the patient has prior macrolide exposure for any indication—cross-resistance is universal within the macrolide family. 1
- Levofloxacin as first-line: Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary). 1, 2
- Patient compliance: Address compliance issues, as more than 10% of patients are poor compliers, leading to much lower eradication rates. 1
- Smoking and obesity: Smoking increases risk of eradication failure (OR 1.95), and high BMI leads to lower drug concentrations at the gastric mucosal level. 1
Adjunctive Therapies
Probiotics can be used to reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve patient compliance, but are of unproven benefit for improving eradication rates. 1, 2, 3