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

Treatment of Helicobacter pylori Infection

The preferred first-line treatment for H. pylori infection is a 14-day bismuth quadruple therapy regimen containing a proton pump inhibitor, bismuth subsalicylate, tetracycline, and metronidazole, which has an eradication rate of 85%. 1

First-Line Treatment Options

Treatment selection should be based on local clarithromycin resistance patterns:

In areas with high clarithromycin resistance (≥15%):

• Bismuth quadruple therapy (14 days) 1, 2

  • Proton pump inhibitor (twice daily)
  • Bismuth subsalicylate
  • Tetracycline (4 times daily)
  • Metronidazole

• Concomitant non-bismuth quadruple therapy (14 days) 1, 2

  • Proton pump inhibitor
  • Amoxicillin
  • Metronidazole
  • Clarithromycin

In areas with low clarithromycin resistance (<15%):

• Triple therapy (14 days) 1, 3

  • Proton pump inhibitor
  • Clarithromycin (500 mg twice daily)
  • Amoxicillin (1 g twice daily)

• Alternative triple therapy (FDA approved) 3

  • Amoxicillin (1 g)
  • Clarithromycin (500 mg)
  • Lansoprazole (30 mg)
  • All given twice daily for 14 days

Diagnostic Testing Before Treatment

Before initiating treatment:

• Stop proton pump inhibitors for at least 2 weeks to avoid false-negative results 1
• Use urea breath test or monoclonal antibody-based stool antigen test for diagnosis (sensitivity 95%, specificity 90%) 1
• If PPIs cannot be stopped, validated IgG serology can be performed 1

Treatment Failure Management

If first-line therapy fails:

• Use a different regimen than the initial treatment 1
• Second-line options include:
  • 14-day levofloxacin triple therapy if bismuth quadruple therapy was used initially 1, 4
  • 14-day bismuth quadruple therapy if not previously used 1

After two treatment failures:

• Obtain antimicrobial susceptibility testing to guide further treatment 1, 5
• If testing is unavailable, use antibiotics not previously used or for which resistance is unlikely (amoxicillin, tetracycline, bismuth, or furazolidone) 2
• Consider "optimized" bismuth quadruple therapy for 14 days for treatment-experienced patients 1, 5

Post-Treatment Follow-up

• Perform a follow-up test to confirm bacterial eradication at least 4 weeks after completion of treatment 1
• Use urea breath test or monoclonal stool antigen test (sensitivity 90%, specificity 95%) 1

Special Considerations

• Take medications at the start of a meal to minimize gastrointestinal intolerance 3
• For patients with penicillin allergy, consider penicillin allergy testing to potentially enable the use of amoxicillin-containing regimens 1
• Common side effects include diarrhea, skin rash, vomiting, nausea, metallic taste, and muscle/joint pains 1
• Probiotics may help reduce side effects, though evidence is limited 1
• For gastric ulcers, continue proton pump inhibitor therapy until complete healing 1
• For duodenal ulcers, continue proton pump inhibitor therapy until bacterial eradication is confirmed 1

Cautions and Pitfalls

• Increasing antibiotic resistance is a major cause of treatment failure 6, 7, 8
• Clarithromycin resistance cannot be overcome by increasing dose or duration 7
• Metronidazole resistance can sometimes be overcome by increasing dose and duration with acid suppression 7
• Ensure patient compliance with the full treatment course to maximize eradication rates
• Patients over 45 years with severe symptoms or any patients with alarm symptoms (anemia, weight loss, dysphagia) should be referred for endoscopy before treatment 1