What is the second line treatment for Helicobacter (H.) pylori when first line treatment fails?

Second-Line Treatment for H. pylori Infection After First-Line Failure

After failure of a PPI-clarithromycin containing therapy, either a bismuth-containing quadruple therapy or levofloxacin-containing triple therapy is recommended as second-line treatment for H. pylori infection. 1

Second-Line Treatment Options Based on First-Line Failure

If First-Line Was Clarithromycin-Based Triple Therapy:

• Bismuth quadruple therapy is recommended (PPI, bismuth salt, tetracycline, and metronidazole) 1
• This regimen meets the criteria for effective second-line treatment as it:
  • Does not contain the key antibiotic of the original regimen (clarithromycin)
  • Is not affected by clarithromycin resistance
  • Metronidazole resistance in vitro does not significantly affect outcome when adequate dosages and durations are used 1

If First-Line Was Bismuth Quadruple Therapy:

• Levofloxacin-containing triple therapy (PPI, levofloxacin, amoxicillin) for 10 days is recommended 1
• Rising rates of levofloxacin resistance should be taken into account when prescribing this regimen 1
• Whenever possible, it is recommended to test levofloxacin susceptibility before prescribing 1

Dosing and Duration Considerations

• High-dose PPI (twice daily) should be used to increase efficacy of therapy 1
• Treatment duration of 10-14 days is recommended for optimal eradication rates 1
• For bismuth quadruple therapy, adequate dosing of metronidazole can overcome resistance 1

Special Considerations

For Patients with Penicillin Allergy:

• If second-line therapy is needed, a levofloxacin-containing regimen (with PPI and clarithromycin) can be used in areas of low fluoroquinolone resistance 1
• Bismuth-containing quadruple therapy is preferred in areas of high clarithromycin resistance 1

Important Cautions:

• Levofloxacin should not be used in patients with chronic respiratory conditions who may have previously received fluoroquinolones 1
• Avoid reusing antibiotics that failed in previous treatment attempts, particularly clarithromycin and levofloxacin, as resistance is common after exposure 1
• Metronidazole may be reused if given with bismuth due to synergistic effects 1

Confirmation of Eradication

• Urea breath test (UBT) or laboratory-based validated monoclonal stool test should be performed at least 4 weeks after completion of therapy to confirm eradication 1
• Serology is not recommended for confirming eradication 1

Third-Line Options (If Second-Line Fails)

• After failure of second-line therapy, treatment should be guided by antimicrobial susceptibility testing whenever possible 1
• If susceptibility testing is not available, empirical use of antibiotics not previously used is recommended 1
• Options include rifabutin-based regimens or high-dose dual therapy (PPI and amoxicillin) 1, 2

By following this algorithmic approach and selecting the appropriate second-line therapy based on previous treatment history and local resistance patterns, optimal H. pylori eradication rates can be achieved to reduce morbidity and mortality associated with persistent infection.