What is the treatment for invasive aspergillosis?

Treatment of Invasive Aspergillosis

Voriconazole is the first-line treatment for invasive aspergillosis with a loading dose of 6 mg/kg IV every 12 hours on day 1, followed by 4 mg/kg IV every 12 hours thereafter (or 200 mg orally twice daily). 1

First-Line Treatment Options

Primary Therapy

• Voriconazole
  • Loading dose: 6 mg/kg IV every 12 hours for 1 day
  • Maintenance: 4 mg/kg IV every 12 hours or 200 mg orally twice daily
  • Superior efficacy and better survival profile compared to other options 1
  • Demonstrated 70.8% survival rate at 12 weeks compared to 57.9% with conventional amphotericin B 1

Alternative Primary Options

• Isavuconazole: Similar efficacy to voriconazole 1
• Liposomal Amphotericin B (L-AMB): 3-5 mg/kg/day IV when voriconazole is contraindicated 2
• Posaconazole: Recent evidence shows non-inferiority to voriconazole for all-cause mortality with fewer treatment-related adverse events 3

Treatment Duration and Monitoring

• Minimum treatment duration: 6-12 weeks 1
• In immunosuppressed patients, continue throughout immunosuppression period until lesions resolve 1
• Monitor treatment response with:
  • Serial clinical evaluation
  • CT imaging at regular intervals
  • Serial serum galactomannan assays 1

Special Considerations

Therapeutic Drug Monitoring

• Target voriconazole trough levels: >1-2 mg/L for efficacy 4
• Avoid levels >5-5.5 mg/L to prevent toxicity 4
• Monitor liver function tests regularly during voriconazole therapy 1

Adverse Events

• Voriconazole: Transient visual disturbances, hepatotoxicity, drug interactions 1
• Amphotericin B: Nephrotoxicity, infusion-related reactions 2
• Posaconazole: Increased liver enzymes, nausea, hypokalaemia 3

Salvage Therapy Options

For patients who fail initial therapy or are intolerant to first-line agents:

Caspofungin

• Loading dose: 70 mg IV on day 1
• Maintenance: 50 mg IV daily 5
• Effective in 50% of patients who received >7 days of therapy after failing other antifungals 5

Other Salvage Options

• Lipid formulations of Amphotericin B
• Posaconazole (400 mg twice daily)
• Micafungin 1

Combination Therapy

• Not recommended as initial treatment 1
• Consider in salvage settings or refractory cases 1
• Voriconazole plus anidulafungin showed improved survival in some subgroups of patients, though limitations in statistical power prevent definitive conclusions 6

Surgical Management

Consider surgical intervention in specific situations 2:

• 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

Pediatric Considerations

For children 3 months to 17 years 5:

• Loading dose: 70 mg/m² (not to exceed 70 mg)
• Maintenance: 50 mg/m² daily (not to exceed 70 mg)

Key Prognostic Factors

• Reversal of immunosuppression (if feasible) is crucial for favorable outcomes 1
• Galactomannan values, Karnofsky score, and baseline platelet count have prognostic significance 6

Remember that early initiation of appropriate antifungal therapy is critical while diagnostic evaluation is conducted, as delayed treatment can significantly impact mortality and morbidity outcomes.