What is the management of invasive pulmonary aspergillosis?

Management of Invasive Pulmonary Aspergillosis

Voriconazole is the first-line treatment for invasive pulmonary aspergillosis in most patients due to its superior efficacy and better survival outcomes compared to other therapeutic options. 1

Primary Treatment Options

First-Line Therapy

• Voriconazole:
  • Loading dose: 6 mg/kg IV every 12 hours on day 1
  • Maintenance dose: 4 mg/kg IV every 12 hours thereafter 1
  • Therapeutic drug monitoring recommended 2
  • Visual disturbances may occur; regular liver function tests should be performed 1

Alternative First-Line Options

• Isavuconazole: Similar efficacy to voriconazole 1
• Liposomal Amphotericin B (L-AMB): 3-5 mg/kg/day IV
  • Consider when azole resistance is suspected or voriconazole is contraindicated 2
  • Similar efficacy between 3 mg/kg/day and 10 mg/kg/day, but higher toxicity at higher doses 2, 1

Salvage Therapy for Refractory Disease

When initial therapy fails, options include:

1. Change of antifungal class:

   • Lipid formulations of Amphotericin B 2, 1
   • Echinocandins: Caspofungin or micafungin 2, 3
     • Caspofungin is FDA-approved for patients refractory to or intolerant of other therapies 3
     • Caspofungin dosing: 70 mg loading dose on day 1, followed by 50 mg daily 3

2. Posaconazole: 400 mg twice daily 1

   • Take with fatty food for optimal intestinal absorption 4
   • Therapeutic drug monitoring recommended 2

3. Combination therapy: Consider in salvage settings, though evidence is limited 2, 1

Treatment Duration and Monitoring

• Minimum treatment duration: 6-12 weeks 1
• In immunosuppressed patients: Continue throughout the period of immunosuppression until lesions have resolved 1
• Monitoring:
  • Serial clinical evaluation of symptoms and signs
  • CT imaging at regular intervals
  • Serial serum galactomannan assays (progressive increase indicates poor prognosis) 1
  • Note: Volume of pulmonary infiltrates may increase during the first 7-10 days of therapy, which does not necessarily indicate treatment failure 1

Surgical Intervention

Consider surgical intervention in specific situations:

• Lesions in proximity to great vessels or pericardium
• Persistent hemoptysis from a single cavitary lesion
• Invasion of chest wall from contiguous pulmonary lesion
• Resection of a single pulmonary lesion prior to intensive chemotherapy or HSCT 1, 5

Special Considerations

Pediatric Patients

• Voriconazole is recommended as first-line treatment for all children except neonates 2
• Liposomal amphotericin B is first choice for neonates 2
• Dosing adjustments required based on age and weight 2

Immunosuppression Management

• Reversal of immunosuppression, if feasible, is crucial for favorable outcomes 1
• In neutropenic patients, consider administration of colony-stimulating factors 2

Drug Interactions

• Significant interactions between voriconazole and other medications, particularly anticonvulsants in patients with CNS involvement 1
• Monitor for interactions with immunosuppressants (e.g., tacrolimus) 3

Treatment Response Assessment

• Assess response approximately 2 weeks after treatment initiation 2
• Composite outcome parameters including clinical, radiological, and mycological criteria should be used 2
• Resolution of galactomannan antigenemia to normal levels alone is not sufficient for discontinuation of therapy 1

The management of invasive pulmonary aspergillosis requires prompt initiation of appropriate antifungal therapy, careful monitoring, and consideration of surgical intervention in specific cases. Voriconazole remains the cornerstone of treatment, with several alternative options available for patients who cannot tolerate or fail to respond to first-line therapy.