In a patient with recurrent allergic bronchopulmonary aspergillosis, should amphotericin B be added to the treatment regimen?

Amphotericin B is NOT Recommended for Recurrent ABPA

Amphotericin B should not be added to the treatment regimen for recurrent allergic bronchopulmonary aspergillosis (ABPA). The most recent 2024 guidelines from the European Respiratory Society explicitly state that nebulized amphotericin B has poor efficacy in acute ABPA 1, and systemic amphotericin B has no role in this allergic condition.

Why Amphotericin B is Not Indicated

ABPA is fundamentally an allergic/immunologic disorder, not an invasive fungal infection 1. The pathophysiology involves hypersensitivity reactions to Aspergillus fumigatus rather than tissue invasion, which is why:

• Systemic amphotericin B (IV formulations) is reserved exclusively for invasive aspergillosis in severely immunocompromised patients with CD4+ counts <50 cells/µL 1 or chronic pulmonary aspergillosis with progressive disease 1
• Nebulized amphotericin B deoxycholate showed poor efficacy for acute ABPA treatment in clinical trials 1
• The 2024 ISHAM-ABPA guidelines do not recommend amphotericin B as first-line, second-line, or rescue therapy for ABPA 1

Appropriate Management of Recurrent ABPA

First-Line Options for Recurrent Exacerbations

Oral prednisolone (0.5 mg/kg/day for 2-4 weeks, tapered over 4 months) or oral itraconazole (400 mg/day for 4 months) remain the recommended treatments 1. For patients experiencing recurrent exacerbations:

• Combination therapy with prednisolone plus itraconazole may be considered specifically for patients with blood eosinophil count ≥1000 cells/µL and extensive bronchiectasis (≥10 segments) 1
• Long-term itraconazole is the preferred maintenance option to reduce exacerbations and oral glucocorticoid requirements 2

The One Exception: Nebulized Liposomal Amphotericin B for Maintenance

The only scenario where amphotericin B has demonstrated benefit in ABPA is:

• Nebulized liposomal amphotericin B (25-50 mg once or twice weekly) for maintenance therapy in treatment-dependent ABPA 1, 2
• The NEBULAMB trial showed this formulation significantly prolongs time-to-first exacerbation 2
• This is NOT the same as systemic IV amphotericin B and is used for prevention, not acute treatment 1

Alternative Approaches for Recurrent Disease

For patients with frequent exacerbations despite standard therapy:

• Biological agents (omalizumab, mepolizumab, benralizumab, dupilumab) have emerging evidence for reducing exacerbations and steroid requirements 2
• Voriconazole, posaconazole, or isavuconazole may be used if there is intolerance, failure, or resistance to itraconazole 1
• Therapeutic drug monitoring is mandatory for all azole therapy to ensure adequate levels 1

Critical Pitfalls to Avoid

1. Do not confuse ABPA with invasive aspergillosis: Amphotericin B is indicated for invasive disease with tissue invasion 1, not for the allergic/hypersensitivity process of ABPA
2. Do not use nebulized amphotericin B deoxycholate for acute ABPA: Despite some small case series 3, 4, 5, the 2024 guidelines explicitly state it has poor efficacy 1
3. Distinguish ABPA exacerbations from other causes: Worsening symptoms may be due to asthma exacerbation or infective bronchiectasis exacerbation, which require different management 1