What is the duration and endpoint of oral macrolide (e.g. azithromycin) therapy in patients with non-cystic fibrosis (non-CF) bronchiectasis?

Duration and Endpoint of Oral Macrolides in Non-CF Bronchiectasis

Oral macrolides should be given for at least 6-12 months in non-CF bronchiectasis patients with frequent exacerbations, with regular reassessment to determine ongoing clinical benefit. 1

Recommended Duration of Therapy

• The European Respiratory Society (ERS) guidelines recommend macrolide therapy for a minimum of 6 months in adults with bronchiectasis 1
• Long-term studies have evaluated macrolide therapy for periods ranging from 6-12 months, with consistent benefits in reducing exacerbations 1
• For children with bronchiectasis, treatment courses of at least 6 months are recommended with evaluation for longer courses (>24 months) based on ongoing risk-benefit assessment 1

Patient Selection Criteria

• Macrolides should be considered specifically for patients who have had:
  • Three or more non-hospitalized exacerbations in the previous 12 months, OR
  • At least one hospitalization for an exacerbation in the previous year 1, 2
• For patients with chronic Pseudomonas aeruginosa infection, inhaled antibiotics are first-line, with macrolides suggested when inhaled antibiotics are contraindicated, not tolerated, or not feasible 2
• For non-Pseudomonas infected patients, macrolides are suggested as first-line long-term antibiotic therapy 2

Dosing Regimens with Strongest Evidence

• Azithromycin 250mg daily for up to 12 months 1
• Azithromycin 500mg three times weekly for 6-12 months 1, 3
• Azithromycin 250mg three times weekly (pragmatic approach with lower evidence base) 1
• Erythromycin ethylsuccinate 400mg twice daily for 12 months 1

Endpoints for Therapy

• The primary endpoint for determining efficacy is reduction in exacerbation frequency 1
• Secondary endpoints include:
  • Improvement in quality of life measures 1
  • Reduction in sputum volume 1
  • Stabilization or improvement in lung function 1

Monitoring and Reassessment

• Regular reassessment (typically every 6 months) to determine whether the antibiotic continues to provide clinical benefit 1, 2
• Monitoring for macrolide resistance in respiratory pathogens 1, 4
• Assessment for adverse effects, particularly:
  • Gastrointestinal symptoms (reported in up to 40% of patients on azithromycin) 4
  • QT interval prolongation (ECG recommended before starting therapy) 2
  • Development of macrolide-resistant bacteria (rates up to 88% reported with long-term use) 4

Important Considerations and Cautions

• Patients should be screened for non-tuberculous mycobacteria (NTM) before starting macrolide therapy, as macrolides should never be used as monotherapy in NTM infections 2
• Treatment efficacy should be assessed based on exacerbation frequency, with evidence showing reduction in exacerbations by up to 60% 3, 4
• There is evidence that benefits may persist for some time after discontinuation, with one study showing reduced exacerbations over 12 months when therapy was used for only the first 6 months 1
• Azithromycin appears more effective than erythromycin in preventing exacerbations based on adjusted indirect treatment comparisons 5

Conclusion for Clinical Practice

• Start with a 6-month course of macrolide therapy in appropriate patients
• Reassess at 6 months for clinical benefit (primarily reduction in exacerbations)
• If beneficial, continue for at least 12 months with ongoing reassessment
• For longer courses (>24 months), continue regular evaluation of risk versus benefit 1, 2