What is the treatment (Tx) for a patient with Invasive Pulmonary Aspergillosis?

Treatment for Invasive Pulmonary Aspergillosis

Voriconazole (D) is the recommended first-line treatment for invasive pulmonary aspergillosis due to its superior efficacy and better survival profile compared to other therapeutic options. 1, 2

Primary Treatment Algorithm

1. 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
   • Can transition to oral therapy at 4 mg/kg twice daily when clinically stable 1, 2
   • For seriously ill patients, the parenteral formulation is strongly recommended 1

2. Alternative primary therapy options (if voriconazole is contraindicated):

   • Liposomal Amphotericin B (L-AMB) at 3-5 mg/kg/day IV 1, 2
   • Isavuconazole (similar efficacy to voriconazole) 2

Treatment Duration

• Minimum of 6-12 weeks 1, 2
• In immunosuppressed patients, continue throughout the period of immunosuppression and until lesions have resolved 1

Monitoring Treatment Response

• Serial clinical evaluation of symptoms and signs
• CT imaging at regular intervals (frequency individualized based on disease progression)
• Monitor voriconazole serum levels, especially in patients with hepatic dysfunction 2
• Serial serum galactomannan assays may be helpful for therapeutic monitoring 1

Salvage Therapy (for refractory cases)

If initial therapy fails, options include:

• Lipid formulations of Amphotericin B 1, 2
• Posaconazole (400 mg twice daily) 1, 2, 3
• Caspofungin (indicated specifically for invasive aspergillosis in patients refractory to or intolerant of other therapies) 1, 4
• Micafungin 1
• Consider combination therapy in salvage settings 1

Important Clinical Considerations

• Early initiation of therapy is critical while diagnostic evaluation is conducted 1
• Volume of pulmonary infiltrates may increase during the first 7-10 days of therapy, which does not necessarily indicate treatment failure 1, 2
• Common side effects of voriconazole include transient visual disturbances (44.8% of patients) 5
• Voriconazole has demonstrated significantly better outcomes compared to conventional amphotericin B, with better survival (70.8% vs 57.9% at 12 weeks) and higher response rates (52.8% vs 31.6%) 2, 5
• In rare cases, surgical resection may be considered for lesions contiguous with great vessels or pericardium, single cavitary lesions causing hemoptysis, or lesions invading the chest wall 3

Caveats and Pitfalls

• Rifampicin (A), Cyclovir (B), and Tigecycline (C) are not indicated for treatment of invasive pulmonary aspergillosis
• Caspofungin is only indicated for salvage therapy, not as primary treatment 4
• Monitor for drug interactions, particularly with anticonvulsants in patients with CNS involvement 2
• Regular liver function tests should be performed during voriconazole therapy 2
• Reversal of immunosuppression, if feasible, is important for favorable outcomes 2