H. pylori: Important Points for Exam
First-Line Treatment Regimens
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori eradication, particularly in areas with high clarithromycin resistance (≥15%). 1, 2
Bismuth Quadruple Therapy Components:
- PPI twice daily (standard or double dose) 1
- Bismuth subsalicylate 262 mg, 2 tablets OR bismuth subcitrate 120 mg, 1 tablet four times daily 1
- Metronidazole 500 mg three to four times daily 1, 2
- Tetracycline 500 mg four times daily 1, 2
- Duration: 14 days (preferred over 10 days for ~5% improvement in eradication) 1, 2
This regimen achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect. 3
Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy
When bismuth is unavailable: 1, 2
- PPI twice daily
- Amoxicillin 1000 mg twice daily
- Clarithromycin 500 mg twice daily
- Metronidazole 500 mg twice daily
- Duration: 14 days
Critical caveat: Only use in areas with clarithromycin resistance <15%, as resistance >15% makes this regimen unacceptably ineffective. 1, 3
Outdated First-Line: Standard Triple Therapy
Standard triple therapy (PPI + clarithromycin + amoxicillin) should be abandoned when regional clarithromycin resistance exceeds 15-20%. 1, 3 This threshold has been surpassed in most of North America and Europe, where resistance now exceeds 20%. 3
Second-Line Treatment After First Failure
All guidelines agree: avoid re-using antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1
Second-Line Options:
Bismuth quadruple therapy (if not used first-line) for 14 days 1, 2
Levofloxacin triple therapy (if bismuth/metronidazole used first-line): 1, 2
- PPI twice daily
- Amoxicillin 1000 mg twice daily
- Levofloxacin 500 mg once daily OR 250 mg twice daily
- Duration: 14 days
Important warning: Levofloxacin resistance is rapidly increasing (11-30% primary, 19-30% secondary resistance), so susceptibility testing should be strongly considered before using this regimen. 1, 3
Third-Line and Salvage Therapy
After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 4
Salvage Options When Testing Unavailable:
- High-dose dual therapy: PPI (high dose twice daily) + amoxicillin 1000 mg three times daily for 14 days 1, 3
- Rifabutin triple therapy: PPI + amoxicillin + rifabutin (restricted to multiple failures) 1, 3
- Use antibiotics not previously used: amoxicillin, tetracycline, bismuth, or furazolidone (resistance to these remains rare) 1, 4
Special Populations
Penicillin Allergy:
- First choice: Bismuth quadruple therapy (contains tetracycline, not amoxicillin) 1
- Alternative in low clarithromycin resistance areas: PPI + clarithromycin + metronidazole 1
- Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare. 3
Pediatric Patients:
- Cannot use: Fluoroquinolones or tetracyclines 1, 2
- First-line options: PPI + amoxicillin + clarithromycin OR PPI + amoxicillin + metronidazole OR bismuth + amoxicillin + metronidazole 1
- Susceptibility testing for clarithromycin is recommended before use. 1
Critical Treatment Optimization Factors
PPI Dosing:
High-dose PPI (twice daily) is mandatory—standard once-daily dosing is inadequate. 2, 5 This increases eradication efficacy by 6-12% by reducing gastric acidity and enhancing antibiotic activity. 5, 3
Standard PPI doses: 1
- Esomeprazole 20-40 mg
- Omeprazole 20-40 mg
- Lansoprazole 30 mg
- Pantoprazole 40 mg
- Rabeprazole 20 mg
Treatment Duration:
14-day regimens are superior to 7-10 day regimens, improving eradication by approximately 5%. 1, 2, 5
Adjunctive Probiotics:
Probiotics reduce antibiotic-related side effects (especially diarrhea, which occurs in 21-41% of patients) and may increase eradication rates by 5-10%. 1, 2, 4
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. 2, 5, 3
Never use serology to confirm eradication—antibodies persist long after successful treatment. 2, 5
Antibiotic Resistance Patterns (Critical for Exam)
Global Resistance Rates:
- Clarithromycin: 10-34% (primary), 15-67% (secondary)—increased from 9% (1998) to 17.6% (2008-2009) 5, 3
- Levofloxacin: 11-30% (primary), 19-30% (secondary) 3
- Metronidazole: 23-56% (primary), 30-65% (secondary) 3
- Amoxicillin: 1-5% (remains low) 3
- Tetracycline: 1-5% (remains low) 3
- Bismuth: No resistance described 1
When H. pylori is clarithromycin-resistant, eradication rates drop from 90% to approximately 20%. 3
Common Pitfalls to Avoid
Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance. 3
Never repeat clarithromycin if patient has prior macrolide exposure for any indication—cross-resistance is universal within the macrolide family. 3
Never use standard-dose PPI once daily—always use twice-daily dosing. 3
Never use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance. 3
Metronidazole can be re-used with bismuth (unlike clarithromycin/levofloxacin) because bismuth's synergistic effect overcomes in vitro resistance. 1
Amoxicillin and tetracycline can be re-used because resistance to these agents remains rare. 1
Risk Factors for Treatment Failure
- Smoking: Odds ratio 1.95 for eradication failure 3
- High BMI/obesity: Lower drug concentrations at gastric mucosal level 3
- Poor compliance: >10% of patients are poor compliers 3
- Prior antibiotic exposure: Especially macrolides and fluoroquinolones 1, 3
FDA-Approved H. pylori Regimens
Triple Therapy (Adults):
Amoxicillin 1 gram + clarithromycin 500 mg + lansoprazole 30 mg, all twice daily for 14 days 6
Dual Therapy (Adults with clarithromycin allergy/intolerance):
Amoxicillin 1 gram + lansoprazole 30 mg, three times daily for 14 days 6