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

Treatment for H. pylori Infection

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in most patients, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1

First-Line Treatment Regimens

Preferred Option: Bismuth Quadruple Therapy

• Bismuth quadruple therapy achieves eradication rates of 80-90% even against metronidazole-resistant strains due to the synergistic effect of bismuth with other antibiotics, and bacterial resistance to bismuth is extremely rare 1
• The regimen consists of:
  • PPI twice daily
  • Bismuth subsalicylate
  • Metronidazole (higher doses of 1.5-2 g daily in divided doses improve eradication rates even with resistant strains) 1
  • Tetracycline
  • Duration: 14 days is strongly preferred over 10 days to maximize eradication rates 1

Alternative First-Line Options When Bismuth is Unavailable

• Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available, consisting of PPI twice daily, amoxicillin 1000 mg twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily 1
• This regimen should only be used if the patient has not been previously exposed to clarithromycin, as prior exposure significantly increases resistance risk 1

Clarithromycin-Based Triple Therapy (Limited Use)

• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 1
• Triple therapy (PPI + clarithromycin + amoxicillin) may only be considered in areas with documented low clarithromycin resistance (<15%), and should be given for 14 days 1, 2
• Clarithromycin resistance dramatically reduces treatment success rates from approximately 90% to 20% 2

FDA-Approved Regimens for H. pylori

• Triple therapy: 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily for 14 days 3
• Dual therapy (for patients allergic or intolerant to clarithromycin): 1 gram amoxicillin and 30 mg lansoprazole, each given three times daily for 14 days 3

Optimizing Treatment Success

PPI Dosing and Timing

• High-dose PPI (twice daily) is essential to reduce gastric acidity and enhance antibiotic activity 1, 2
• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 3

Treatment Duration

• Extending treatment duration from 7 to 14 days improves eradication success by approximately 5% 1, 2
• Treatment should be continued for a minimum of 48-72 hours beyond symptom resolution or evidence of bacterial eradication 3

Antibiotic Selection Principles

• Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance is likely to have developed 1, 2
• Avoid using levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates 1
• Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 1

Second-Line and Rescue Therapies

After First Treatment Failure

• If bismuth quadruple therapy was not used initially, it should be the second-line choice 1
• Levofloxacin-based triple therapy (PPI + amoxicillin + levofloxacin) for 14 days is an alternative second-line option in areas with low levofloxacin resistance and if not previously used 1, 4
• Rifabutin triple therapy (rifabutin 150 mg twice daily + amoxicillin + PPI) for 14 days is an acceptable alternative, as resistance to rifabutin and amoxicillin remains rare 1

After Two Treatment Failures

• Antibiotic susceptibility testing is strongly recommended after two failed eradication attempts to guide further treatment 1, 2
• If susceptibility testing is unavailable, use antibiotics not previously used or for which resistance is unlikely (amoxicillin, tetracycline, bismuth, or furazolidone) 5
• High-dose dual therapy with amoxicillin and PPI is an alternative rescue option 1

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 1, 2
• This test-of-cure is essential to document successful eradication and guide further management if needed 1

Managing Side Effects

• Diarrhea occurs in 21-41% of patients during the first week of H. pylori eradication therapy due to disruption of normal gut microbiota 1
• Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance 1, 2
• Side effects led to treatment discontinuation in approximately 5% of patients across different regimens 6

Special Populations

Renal Impairment

• Patients with GFR 10-30 mL/min: 500 mg or 250 mg amoxicillin every 12 hours 3
• Patients with GFR <10 mL/min: 500 mg or 250 mg amoxicillin every 24 hours 3
• Hemodialysis patients: Administer an additional dose both during and at the end of dialysis 3
• Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose 3

Penicillin Allergy

• For patients with documented penicillin allergy, metronidazole can be substituted for amoxicillin in triple therapy regimens 1
• Dual therapy with lansoprazole is FDA-approved for patients allergic or intolerant to clarithromycin 3

Critical Pitfalls to Avoid

• Do not use 7-day treatment regimens - 14 days is the evidence-based standard 1, 2
• Do not use clarithromycin-based regimens in areas with >15% resistance without susceptibility testing 1, 2
• Do not assume all penicillin allergies are valid - verify history and consider allergy testing to enable amoxicillin use 1
• Do not use sequential or hybrid therapies as they include unnecessary antibiotics that contribute to global antibiotic resistance 1
• Do not forget to confirm eradication - treatment failure without documentation leads to persistent infection and increased cancer risk 1, 2