What is the recommended treatment for a patient with pulmonary aspergillosis, particularly one with a compromised immune system or severe symptoms?

Treatment of Pulmonary Aspergillosis

Voriconazole is the first-line treatment for invasive pulmonary aspergillosis in immunocompromised patients, demonstrating superior survival (71% vs 58% at 12 weeks) and response rates (53% vs 32%) compared to amphotericin B. 1, 2

Invasive Pulmonary Aspergillosis (IPA)

Primary Treatment

Initiate antifungal therapy immediately when invasive aspergillosis is strongly suspected—do not wait for diagnostic confirmation, as delays increase mortality risk. 1

Voriconazole Dosing (First-Line)

• Loading dose: 6 mg/kg IV every 12 hours for the first 24 hours 1, 3
• Maintenance dose: 4 mg/kg IV every 12 hours for minimum 7 days 1, 3
• Oral transition: 200 mg orally twice daily once stable (can round up 4 mg/kg to convenient pill sizes) 1
• Pediatric dosing (≥2 years): 5-7 mg/kg IV every 12 hours 4
• Therapeutic drug monitoring is mandatory due to variable pharmacokinetics and narrow therapeutic window 4, 5

Alternative First-Line Options

• Liposomal amphotericin B (L-AmB): 3-5 mg/kg/day IV is an acceptable alternative when voriconazole is contraindicated or not tolerated 1, 4
• Posaconazole: Recent evidence shows non-inferiority to voriconazole (15% vs 21% mortality at day 42) with fewer treatment-related adverse events (30% vs 40%), making it a viable first-line alternative 6
• Isavuconazole: Comparable efficacy to voriconazole with potentially better safety profile 7

Salvage Therapy (For Refractory or Intolerant Patients)

When initial therapy fails or breakthrough infection occurs on azole prophylaxis, switch to a different antifungal class: 1

• Lipid formulations of amphotericin B: 3-5 mg/kg/day IV 1
• Posaconazole: Useful third-line agent for adverse events or clinical failure 1
• Echinocandins: Caspofungin (70 mg loading dose, then 50 mg/day IV) or micafungin 1
• Itraconazole: Alternative salvage option 1

Treatment Duration

Continue antifungal therapy for minimum 6-12 weeks; in immunosuppressed patients, extend throughout the entire period of immunosuppression and until complete radiographic resolution of lesions. 1, 4, 5 Premature discontinuation leads to relapse and increased mortality. 5

Monitoring

• Serial CT imaging at individualized intervals based on clinical acuity and rapidity of infiltrate evolution 1
• Expect initial radiographic worsening during first 7-10 days of therapy, especially with granulocyte recovery 1
• Galactomannan levels: Progressive increases indicate poor prognosis, but normalization alone is insufficient to discontinue therapy 1

Chronic Cavitary Pulmonary Aspergillosis (CCPA)

Diagnostic Criteria

Requires all three: 1

1. ≥3 months of chronic pulmonary symptoms or progressive radiographic abnormalities (cavitation, pleural thickening, pericavitary infiltrates, fungal ball)
2. Elevated Aspergillus IgG antibody or other microbiological evidence
3. Minimal/no immunocompromise with underlying pulmonary disorder

Treatment Algorithm

Asymptomatic patients without functional decline may be observed with follow-up every 3-6 months without antifungal therapy. 1

Symptomatic patients (pulmonary symptoms, weight loss, fatigue) or those with progressive lung function decline require minimum 6 months of oral antifungal therapy: 1

First-Line Oral Agents

• Itraconazole or voriconazole are preferred 1, 8
• Posaconazole is third-line for adverse events or clinical failure 1

Refractory CCPA

For treatment failures, triazole resistance, or adverse events: 1

• Intravenous options: Micafungin, caspofungin, or amphotericin B formulations 1
• Long-term or lifelong suppressive therapy may be required for progressive disease 1, 8

Hemoptysis Management

• Mild-moderate: Oral tranexamic acid 500 mg three times daily 1, 8
• Severe/life-threatening: Bronchial artery embolization 1, 8
• Refractory cases: Surgical resection if feasible 1

Simple Aspergilloma (Single Cavity with Fungal Ball)

Asymptomatic patients with stable cavity size over 6-24 months should be observed without treatment. 1, 8

Symptomatic patients (especially with significant hemoptysis) require surgical resection via VATS when technically feasible—this is the only curative option. 1, 8 Medical therapy alone is ineffective for simple aspergilloma as amphotericin B penetration into preexisting cavities is minimal. 1, 8

Tracheobronchial Aspergillosis

Voriconazole is the recommended initial therapy for tracheobronchial aspergillosis, particularly in lung transplant recipients. 1 Bronchoscopic evaluation is essential for diagnosis as radiographic imaging may not identify early infection. 1

Critical Pitfalls to Avoid

• Never use amphotericin B deoxycholate as primary therapy—it is inferior to voriconazole with worse survival and more toxicity 1, 2
• Do not delay antifungal initiation while awaiting diagnostic confirmation in suspected invasive disease 1
• Avoid premature discontinuation before completing minimum 6-12 weeks and achieving radiographic resolution 1, 5
• Do not rely solely on galactomannan normalization to stop therapy 1
• Systemic amphotericin B monotherapy is ineffective for aspergilloma 8
• Corticosteroids without adequate antifungal coverage accelerate disease progression 8

Special Populations

Breakthrough Infection on Azole Prophylaxis

Switch to a different antifungal class (amphotericin B formulation or echinocandin) rather than continuing azole therapy. 1

Lung Transplant Recipients

Preemptive therapy with antimold antifungal is recommended for asymptomatic Aspergillus airway colonization within 6 months post-transplant or within 3 months of immunosuppression augmentation for rejection. 1

CNS Aspergillosis

Voriconazole is the primary recommendation for CNS involvement due to superior CNS penetration; surgical resection should be considered for accessible lesions. 1