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 high-dose PPI twice daily, bismuth subsalicylate, tetracycline, and metronidazole. 1, 2
This recommendation is based on:
- High efficacy (80-90% eradication rates) even against clarithromycin and metronidazole-resistant strains due to bismuth's synergistic effect 1, 2
- Clarithromycin resistance now exceeds 15% in most regions, making traditional triple therapy unacceptably ineffective 2, 3
- No bacterial resistance to bismuth has been described, making this regimen reliable across all resistance patterns 1, 2
Specific Dosing Regimen
- PPI (esomeprazole or rabeprazole preferred): 40 mg twice daily, taken 30 minutes before meals on an empty stomach 1, 2
- 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, 2
- Tetracycline: 500 mg four times daily 1, 2
- Duration: 14 days (mandatory—improves eradication by ~5% compared to shorter regimens) 1, 2
Alternative First-Line Option (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available 2, 3:
- PPI: Twice daily (high-dose preferred)
- Amoxicillin: 1000 mg twice daily 2
- Clarithromycin: 500 mg twice daily 2
- Metronidazole: 500 mg twice daily 2
Critical caveat: This regimen should only be used when local clarithromycin resistance is <15%, which is now rare in most regions 2, 3
Second-Line Treatment After First-Line Failure
If Bismuth Quadruple Therapy Was NOT Used First-Line:
Use bismuth quadruple therapy for 14 days (as described above) 1, 2
If Bismuth Quadruple Therapy Failed:
Levofloxacin-based triple therapy for 14 days (if no prior fluoroquinolone exposure) 1, 2:
- PPI: Twice daily (high-dose)
- Amoxicillin: 1000 mg twice daily 1, 2
- Levofloxacin: 500 mg once daily OR 250 mg twice daily 1, 2
Important warning: Levofloxacin resistance is rising (11-30% primary, 19-30% secondary resistance), so avoid if patient has had any prior fluoroquinolone exposure for any indication 1, 2
Third-Line and Rescue Therapies
After Two Failed Attempts:
Antimicrobial susceptibility testing should guide further treatment whenever possible 1, 2
When Susceptibility Testing Unavailable:
Option 1: Rifabutin-based triple therapy for 14 days 1, 2:
- Rifabutin: 150 mg twice daily
- Amoxicillin: 1000 mg twice daily
- PPI: Twice daily (high-dose)
- Advantage: Rifabutin resistance is extremely rare 1
Option 2: High-dose dual amoxicillin-PPI therapy for 14 days 1:
- Amoxicillin: 2-3 grams daily in 3-4 divided doses
- PPI: Double standard dose, twice daily
Critical Optimization Factors
PPI Dosing (Applies to ALL Regimens):
- High-dose PPI twice daily is mandatory—increases eradication efficacy by 6-10% compared to standard dosing 1, 2
- Esomeprazole or rabeprazole 40 mg twice daily preferred—may increase cure rates by an additional 8-12% compared to other PPIs 1, 2
- Timing: Take 30 minutes before meals on an empty stomach, without concomitant antacids 1
Treatment Duration:
- 14 days is mandatory for all regimens—improves eradication by ~5% compared to 7-10 day regimens 1, 2
Antibiotic Selection Principles:
- Never repeat antibiotics previously used, especially clarithromycin and levofloxacin—resistance develops rapidly after exposure 1, 2
- Amoxicillin, tetracycline, and bismuth can be re-used because resistance remains rare (<5%) 1, 2
- Metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes in vitro resistance 1, 2
Verification of Eradication
Confirm eradication with urea breath test or monoclonal stool antigen test: 1, 2
- At least 4 weeks after completion of therapy
- At least 2 weeks after PPI discontinuation
- Never use serology—antibodies persist long after successful treatment 1, 2
Special Populations
Penicillin Allergy:
Bismuth quadruple therapy is the first choice (contains tetracycline, not amoxicillin) 1, 2
Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains rare 1
H. pylori with Amoxicillin for Dual Therapy (FDA-Approved):
For dual therapy: 1 gram amoxicillin three times daily (every 8 hours) with 30 mg lansoprazole three times daily for 14 days 4
For triple therapy: 1 gram amoxicillin twice daily (every 12 hours) with 500 mg clarithromycin and 30 mg lansoprazole, all twice daily for 14 days 4
Common Pitfalls and How to Avoid Them
Pitfall #1: Inadequate PPI Dosing
Solution: Always use high-dose PPI twice daily (not once daily, not standard dose)—this single factor increases efficacy by 6-10% 1, 2
Pitfall #2: Using Clarithromycin-Based Triple Therapy in High-Resistance Areas
Solution: Abandon standard triple therapy when regional clarithromycin resistance exceeds 15%—this threshold has been surpassed in most of North America and Europe 2, 3
Pitfall #3: Repeating Failed Antibiotics
Solution: Avoid clarithromycin and levofloxacin if previously used for ANY indication (not just H. pylori)—cross-resistance is universal within antibiotic classes 1, 2
Pitfall #4: Inadequate Treatment Duration
Solution: Always prescribe 14 days—shorter regimens have unacceptably lower cure rates 1, 2
Pitfall #5: Poor Patient Compliance
Solution: Address compliance issues proactively—more than 10% of patients are poor compliers, leading to much lower eradication rates 1
Consider adjunctive probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients) and improve compliance, though probiotics do not increase eradication rates 2, 3