H. Pylori Eradication: First-Line Treatment
Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori eradication, achieving 80-90% eradication rates even in areas with high antibiotic resistance. 1, 2
Preferred First-Line Regimen: Bismuth Quadruple Therapy
The optimal regimen consists of four components taken for 14 days 1, 2:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred, taken 30 minutes before meals) 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
This regimen is superior because bismuth has no described bacterial resistance, and the synergistic effect overcomes metronidazole resistance even when present 1, 2. The combination remains highly effective against clarithromycin-resistant strains, which now exceed 15-20% prevalence in most of North America and Europe 1.
Alternative First-Line Option (Limited Circumstances Only)
Triple therapy may only be considered in areas with documented clarithromycin resistance below 15% 1, 2:
- High-dose PPI twice daily (esomeprazole or rabeprazole 40 mg) 1
- Clarithromycin 500 mg twice daily 1
- Amoxicillin 1000 mg twice daily 1, 3
- Duration: 14 days mandatory 1
However, this regimen achieves only 70% eradication rates in areas with high clarithromycin resistance and should be abandoned when local resistance exceeds 15% 1.
When Bismuth is Unavailable
Concomitant non-bismuth quadruple therapy for 14 days 1:
- High-dose PPI twice daily 1
- Amoxicillin 1000 mg twice daily 1
- Clarithromycin 500 mg twice daily 1
- Metronidazole 500 mg twice daily 1
This regimen administers all antibiotics simultaneously to prevent resistance development during treatment 1.
Critical Optimization Factors
Treatment duration of 14 days is mandatory—extending from 7 to 14 days improves eradication by approximately 5% 1, 2. Shorter courses are inadequate and increase treatment failure 1.
High-dose PPI twice daily is non-negotiable—standard once-daily dosing significantly reduces efficacy 1. Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs 1.
Take PPI 30 minutes before meals on an empty stomach without concomitant antacids to maximize absorption 1.
Special Populations
For penicillin allergy: Bismuth quadruple therapy is the first choice since it contains tetracycline, not amoxicillin 1, 4. However, consider penicillin allergy testing to enable amoxicillin use, as most reported allergies are not true allergies 1.
For tetracycline unavailability: Rifabutin triple therapy (rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + high-dose PPI twice daily for 14 days) is an acceptable alternative, as rifabutin resistance remains rare 1.
Second-Line Treatment After First-Line Failure
Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2.
If bismuth quadruple therapy was not used first-line, use it as second-line for 14 days 2, 4. If bismuth quadruple therapy fails, levofloxacin triple therapy (PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily for 14 days) is recommended, assuming no prior fluoroquinolone exposure and low local resistance 1, 2.
After Two Failed Attempts
Antibiotic susceptibility testing should guide further treatment whenever possible 1, 2, 4. Third-line options include rifabutin triple therapy or high-dose dual amoxicillin-PPI therapy 1.
Confirmation of Eradication
Test-of-cure is mandatory using urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after discontinuing PPI 1, 2. Never use serology to confirm eradication, as antibodies persist long after successful treatment 1.
Common Pitfalls to Avoid
- Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 1
- Do not use levofloxacin as first-line therapy—this accelerates resistance development and eliminates a valuable rescue option 1
- Do not use concomitant, sequential, or hybrid therapies—these include unnecessary antibiotics that contribute to global antibiotic resistance without therapeutic benefit 1
- Do not use standard-dose PPI once daily—this is inadequate and significantly reduces treatment efficacy 1
Patient Factors Affecting Success
Smoking increases eradication failure risk (odds ratio 1.95) 1. High BMI increases failure risk due to lower drug concentrations at the gastric mucosal level 1, 4. Address compliance issues, as more than 10% of patients are poor compliers, leading to much lower eradication rates 1.