What is the treatment for invasive aspergillosis?

Treatment of Invasive Aspergillosis

Voriconazole is the first-line treatment for invasive aspergillosis, with demonstrated superior efficacy and survival compared to amphotericin B formulations. 1, 2

Primary Treatment Regimen

Voriconazole Dosing (Adults ≥18 years)

• Loading dose: 6 mg/kg IV every 12 hours for the first 24 hours 1, 2
• Maintenance dose: 4 mg/kg IV every 12 hours for minimum 7 days 1, 2
• Oral transition: 200 mg every 12 hours after stabilization 1, 2
• Therapeutic drug monitoring is mandatory due to variable pharmacokinetics and narrow therapeutic window 2, 3
• If 4 mg/kg dose is well tolerated but provides inadequate clinical response, increase to 6 mg/kg IV every 12 hours 1

Pediatric Dosing (≥2 years, 3 months-17 years)

• Voriconazole: 5-7 mg/kg IV every 12 hours (higher than adult weight-based dosing) 1, 3
• Neonates: Use liposomal amphotericin B as first choice, not voriconazole 3

Alternative First-Line Options

When voriconazole is contraindicated or not tolerated:

• Liposomal amphotericin B (L-AMB): 3-5 mg/kg/day IV 1, 2, 3
• Posaconazole: Recent evidence demonstrates non-inferiority to voriconazole with 15% vs 21% mortality at day 42 and fewer treatment-related adverse events (30% vs 40%) 4
  • Dosing: 300 mg IV/oral twice on day 1, then 300 mg once daily 4

Salvage Therapy Options

For voriconazole-refractory disease or treatment failure:

• Liposomal amphotericin B: 3-5 mg/kg/day IV 1, 5
• Caspofungin: 70 mg loading dose day 1, then 50 mg/day IV 1, 6
• Micafungin: 100-150 mg/day IV 1
• Posaconazole: 200 mg QID initially, then 400 mg BID after stabilization 1
• Itraconazole: Dosage depends on formulation 1

Note: Caspofungin is FDA-approved only for invasive aspergillosis in patients refractory to or intolerant of other therapies, not as initial therapy 6

Treatment Duration

• Minimum duration: 6-12 weeks 3, 5
• Continue therapy throughout immunosuppression period and until complete resolution or stabilization of clinical and radiographic findings 1, 3, 5
• Most experts treat until resolution or stabilization of all clinical and radiographic manifestations 1

Site-Specific Considerations

CNS Aspergillosis

• Same antifungal regimen as invasive pulmonary aspergillosis 1
• Highest mortality among all invasive aspergillosis patterns 1, 2
• Monitor for drug interactions with anticonvulsants 1, 2

Cardiac Aspergillosis (Endocarditis, Pericarditis, Myocarditis)

• Same antifungal regimen as invasive pulmonary aspergillosis 1
• Endocardial lesions require surgical resection 1
• Pericarditis usually requires pericardiectomy 1

Aspergillus Osteomyelitis and Septic Arthritis

• Same antifungal regimen as invasive pulmonary aspergillosis 1
• Surgical resection of devitalized bone and cartilage is essential for curative intent 1, 2

Cutaneous Aspergillosis

• Same antifungal regimen as invasive pulmonary aspergillosis 1
• Surgical resection indicated where feasible 1

Surgical Intervention Indications

Consider surgical debridement for:

• Localized disease refractory to medical therapy 2, 3, 7
• Extrapulmonary manifestations (endocarditis, osteomyelitis, mycotic aneurysm) 7
• Obtaining tissue for diagnosis and antifungal susceptibility testing 7

Critical Pitfalls to Avoid

• Never use amphotericin B deoxycholate (dAmB) when other options are available due to substantial nephrotoxicity, particularly with concomitant cyclosporine or tacrolimus 1, 2
• Always perform therapeutic drug monitoring for voriconazole - inadequate blood levels are a common cause of treatment failure 2, 3, 8
• Check for CYP2C19 polymorphisms if voriconazole levels remain subtherapeutic despite dose adjustments 8
• Monitor serum galactomannan levels serially - progressive increases signify poor prognosis 5
• Assess drug susceptibility of causative Aspergillus species in refractory cases, as voriconazole-resistant strains exist 8
• Reversal of immunosuppression is critical for favorable outcomes when feasible 1, 2
• In ECMO patients, standard voriconazole dosing is inadequate - much higher doses (up to 6.5 mg/kg three times daily) may be necessary with mandatory frequent therapeutic drug monitoring 9

Monitoring Response to Treatment

• Serial clinical evaluation of symptoms and signs 5
• Regular radiographic imaging with CT scans 5
• Serial serum galactomannan assays 5, 8
• Voriconazole trough level monitoring (target therapeutic range) 2, 3, 8