Treatment of the Five Types of Aspergillosis
1. Invasive Aspergillosis (Including Invasive Pulmonary Aspergillosis)
Voriconazole is the first-line treatment for invasive aspergillosis, with demonstrated superior efficacy and survival compared to amphotericin B formulations. 1, 2, 3
Primary Therapy
- Voriconazole: Loading dose of 6 mg/kg IV every 12 hours for 24 hours, followed by 4 mg/kg IV every 12 hours for minimum 7 days, then switch to oral 200 mg every 12 hours 1, 2, 3
- Therapeutic drug monitoring is mandatory due to variable pharmacokinetics and narrow therapeutic window 2, 4
- Pediatric dosing (≥2 years): 5-7 mg/kg IV every 12 hours 1, 2
Alternative Primary Therapy
- Liposomal amphotericin B (L-AMB): 3-5 mg/kg/day IV for patients with voriconazole contraindications or intolerance 1, 2, 4
- Caspofungin: 70 mg loading dose day 1, then 50 mg/day IV 1
- Itraconazole: 200 mg IV every 12 hours for 2 days, then 200 mg daily IV or 200 mg PO twice daily 1, 4
- Posaconazole: 200 mg QID initially, then 400 mg BID PO after stabilization 1
Treatment Duration and Key Considerations
- Continue therapy for 6-12 weeks and throughout immunosuppression period until complete resolution or stabilization of clinical and radiographic findings 2, 4, 5
- Reversal of immunosuppression is critical for favorable outcomes 1
- Surgical resection should be considered for localized disease refractory to medical therapy 2
- This infection pattern has the highest mortality among all aspergillosis types when involving the CNS 1
2. Chronic Pulmonary Aspergillosis (Including Chronic Necrotizing and Chronic Cavitary Forms)
Itraconazole or voriconazole are the preferred treatments for chronic pulmonary aspergillosis, as these oral triazoles allow for the protracted therapy required. 1, 6, 5
Primary Therapy
- Itraconazole: 200 mg PO every 12 hours (preferred for long-term oral therapy) 1, 6
- Voriconazole: 200 mg PO every 12 hours 1, 5
Alternative Therapy
- Same options as invasive pulmonary aspergillosis can be used 1
Key Considerations
- Long-term therapy measured in months is required 1
- Innate immune defects are demonstrated in most of these patients 1
- Surgical resection may lead to significant complications and should be approached cautiously 1
- Oral triazoles are preferred over parenteral agents due to the prolonged treatment course needed 1
3. Aspergilloma (Fungus Ball)
Aspergilloma management prioritizes observation or surgical resection, as the role of medical therapy remains uncertain due to poor drug penetration into preexisting cavities. 1
Primary Approach
- No therapy (observation) or surgical resection 1
Alternative Medical Therapy (When Surgery Not Feasible)
- Itraconazole: Standard dosing (excellent cavity penetration) 1
- Voriconazole: Standard dosing 1
- Other agents similar to invasive pulmonary aspergillosis regimens 1
Key Considerations
- Medical therapy efficacy is uncertain due to minimal amphotericin B penetration into cavities, though itraconazole penetration is excellent 1
- Surgical resection is definitive treatment when feasible 6
- Patients typically present with chronic productive cough and hemoptysis with a rounded, sometimes mobile mass in a cavity 6
4. Allergic Bronchopulmonary Aspergillosis (ABPA)
Itraconazole combined with corticosteroids is the treatment of choice for ABPA, with itraconazole providing a demonstrable corticosteroid-sparing effect. 1, 6
Primary Therapy
- Itraconazole: 200 mg PO every 12 hours 1
- Corticosteroids: Cornerstone of therapy, used in combination with itraconazole 1, 6
Alternative Therapy
Key Considerations
- Corticosteroids remain essential for managing the allergic inflammatory response 1, 6
- Itraconazole reduces corticosteroid requirements, minimizing steroid-related side effects 1
- Clinical manifestations include corticosteroid-dependent asthma, fever, hemoptysis, and progressive airway destruction that can evolve to fibrosis 6
5. Allergic Aspergillus Sinusitis
Allergic Aspergillus sinusitis can be managed with observation alone or itraconazole, as there is limited data supporting aggressive antifungal therapy. 1
Primary Approach
- No therapy (observation) or Itraconazole: Standard dosing 1
Key Considerations
- Very limited data exists on treatment efficacy for other antifungal agents 1
- This represents the mildest form of allergic aspergillosis 1
Critical Pitfalls to Avoid Across All Types
- Never use amphotericin B deoxycholate when other options are available due to substantial nephrotoxicity, particularly dangerous with concomitant cyclosporine or tacrolimus use 1, 4
- Always perform therapeutic drug monitoring for voriconazole due to variable pharmacokinetics 2, 4
- Do not delay treatment in invasive disease—early targeted therapy is the most important predictor of successful outcome 5
- Consider surgical intervention for invasive disease involving bone, cartilage, heart valves, or when medical therapy fails 1
- Assess for drug interactions particularly with voriconazole and anticonvulsants in CNS aspergillosis 1