H. pylori Treatment Regimen
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 to four times daily, and tetracycline 500mg four times daily. 1
First-Line Treatment: Bismuth Quadruple Therapy
The American Gastroenterological Association recommends this regimen because it achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1, 2 This is critical because clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective. 2
Specific dosing components:
- PPI: Standard dose twice daily (pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, or rabeprazole 20mg) 1
- Bismuth: Bismuth subsalicylate 262mg or bismuth subcitrate 120mg, four times daily 1
- Metronidazole: 500mg three to four times daily (total 1.5-2g daily) 1
- Tetracycline: 500mg four times daily 1
Critical Optimization Factors
PPI administration is crucial: Take twice daily, 30 minutes before meals on an empty stomach, without concomitant antacids. 1 High-dose PPI (esomeprazole or rabeprazole 40mg twice daily) may increase cure rates by an additional 8-12% compared to standard PPIs. 2, 3
14-day duration is mandatory: This improves eradication rates by approximately 5% compared to 7-10 day regimens and is superior across all studies. 1, 2
Why bismuth quadruple therapy works: Bacterial resistance to bismuth is extremely rare, and bismuth's synergistic effect overcomes metronidazole resistance even when present in vitro. 2, 3
Alternative First-Line Option (When Bismuth Unavailable)
Concomitant non-bismuth quadruple therapy for 14 days: 2, 3
- PPI twice daily
- Amoxicillin 1000mg twice daily
- Clarithromycin 500mg twice daily
- Metronidazole 500mg twice daily
Use this only if: Local clarithromycin resistance is documented <15% and the patient has no prior macrolide exposure for any indication. 2, 3
Second-Line Treatment After First-Line Failure
If bismuth quadruple therapy fails, use levofloxacin triple therapy for 14 days: 1, 3
- PPI twice daily
- Amoxicillin 1000mg twice daily 4
- Levofloxacin 500mg once daily or 250mg twice daily
If clarithromycin-based therapy fails, use bismuth quadruple therapy (if not previously used). 1, 2
Critical antibiotic reuse rules: Never reuse clarithromycin or levofloxacin due to high resistance rates after exposure. Amoxicillin and tetracycline can be reused because resistance remains rare (<5%). 1, 3
Third-Line and Rescue Therapies
After two failed attempts, obtain antibiotic susceptibility testing before further treatment. 1, 2 Molecular testing for clarithromycin and levofloxacin resistance can guide therapy selection earlier. 1
Rifabutin triple therapy for 14 days (third-line option): 1, 3
- PPI twice daily
- Amoxicillin 1000mg twice daily
- Rifabutin 150mg twice daily or 300mg once daily
High-dose dual therapy (rescue option): 1, 3
- Amoxicillin 2-3 grams daily in 3-4 divided doses
- PPI high-dose twice daily
- Duration: 14 days
Special Populations
Penicillin allergy: Bismuth quadruple therapy is the first choice because it contains tetracycline instead of amoxicillin. 1, 3 Consider penicillin allergy testing to enable amoxicillin use, as true allergy is often overreported. 3
Pediatric patients: Treatment should only be conducted by pediatric gastroenterologists in specialist centers. 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 Never use serology for confirmation—antibodies persist long after successful treatment. 3
Common Pitfalls to Avoid
Never assume low clarithromycin resistance without local surveillance data—most regions now exceed 15-20% resistance. 2, 3
Avoid standard once-daily PPI dosing—this is inadequate and reduces eradication rates by 6-10%. 2, 3
Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary). 2
Address compliance issues: More than 10% of patients are poor compliers, which dramatically reduces eradication rates. 2 Diarrhea occurs in 21-41% of patients during the first week; consider adjunctive probiotics to reduce side effects and improve compliance. 2
Patient factors affecting success: Smoking increases failure risk (OR 1.95), and high BMI reduces drug concentrations at the gastric mucosal level. 2