What is the recommended treatment for Helicobacter pylori (H. pylori) infection?

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 (262 mg four times daily or bismuth subcitrate 120 mg four times daily), metronidazole (500 mg three to four times daily), and tetracycline HCl (500 mg four times daily). 1, 2

Why Bismuth Quadruple Therapy is Preferred

• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective with eradication rates dropping to approximately 20% with resistant strains compared to 90% with susceptible strains 1

• Bismuth quadruple therapy achieves 80-90% eradication rates even against strains with dual resistance to clarithromycin and metronidazole 1, 2

• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare (<5%) 1

• The regimen uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 1

Critical Optimization Factors

• Use high-dose PPI twice daily (esomeprazole or rabeprazole 40 mg preferred), taken 30 minutes before meals on an empty stomach - this increases cure rates by 8-12% compared to standard PPIs and 6-10% compared to once-daily dosing 1, 3

• 14-day duration is mandatory - extending from 7 to 14 days improves eradication success by approximately 5% 1, 2

• Take all medications at the start of meals to minimize gastrointestinal intolerance 3

Important Caveat About Tetracycline

• Use tetracycline HCl specifically, NOT doxycycline - doxycycline is ineffective for H. pylori eradication despite being a tetracycline derivative and is specifically excluded from effective treatment regimens 4

Alternative First-Line Regimen When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily. 1, 2

When to Use This Alternative

• Only use when bismuth quadruple therapy cannot be obtained 1

• Avoid if the patient has had previous macrolide exposure for any indication, as cross-resistance is universal within the macrolide family 1

• Consider local clarithromycin resistance patterns - this regimen should be abandoned if regional resistance exceeds 15-20% 1

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 or Was Already Used

Levofloxacin triple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily). 1, 5, 2

• Only use if the patient has no prior fluoroquinolone exposure for any indication 1

• Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary), so do not use empirically as first-line therapy 1

• Intention-to-treat cure rates are approximately 74% after non-bismuth quadruple therapy failure 5

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

Antibiotic susceptibility testing should guide further treatment whenever possible. 1, 6, 2

Empiric Rescue Options When Susceptibility Testing is Unavailable

• Rifabutin triple therapy for 14 days: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily - rifabutin resistance is extremely rare 1, 2

• High-dose dual amoxicillin-PPI therapy for 14 days: amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily - amoxicillin resistance remains rare (<5%) 1, 2

Critical Pitfalls to Avoid

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2

• Never use standard-dose PPI once daily - always use twice-daily dosing to maximize gastric pH elevation 1

• Never assume low clarithromycin resistance without local surveillance data - most regions now have high resistance rates 1

• Never use serology to confirm eradication - antibodies persist long after successful treatment 1

Confirmation of Eradication

Test for eradication success at least 4 weeks after completion of therapy using urea breath test or validated monoclonal stool antigen test, and discontinue PPI at least 2 weeks before testing. 1, 2

Managing Side Effects

• Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota 1

• Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance, though evidence for increasing eradication rates is limited 1, 6

Special Populations

Patients with Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 1

• Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains rare 1

Patients with Renal Impairment

• Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose 3

• For GFR 10-30 mL/min: amoxicillin 500 mg or 250 mg every 12 hours 3

• For GFR <10 mL/min or hemodialysis: amoxicillin 500 mg or 250 mg every 24 hours, with an additional dose during and at the end of dialysis 3

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95) - counsel patients to stop smoking during treatment 1

• High BMI increases risk of failure due to lower drug concentrations at the gastric mucosal level 1

• Poor compliance accounts for more than 10% of treatment failures - emphasize the importance of taking all medications correctly 1