Therapy of Invasive Aspergillosis: Current Consensus and Controversies

Invasive aspergillosis (IA) has emerged as an important infection, accounting for 20 to 40% of systemic fungal infections in patients with acute leukemia, 10 to 20% in blood and marrow transplant (BMT) recipients, and 5 to 15% in solid organ transplant recipients. This chapter provides a conceptual framework for the consensus and controversies in primary and salvage therapies for this infection. A large randomized multicenter study comparing the triazole voriconazole (VRC) to amphotericin-deoxycholate (DAMB; given at relatively high doses of 1 to 1.5 mg/kg of body weight/day), followed by other licensed antifungal therapy (mostly lipid formulations of AMB) for patients with lack of response or toxicity, showed a survival advantage in patients randomized to the VRC arm. The modern way of giving AMB-based therapy, especially if a patient is to be committed to weeks or even months of therapy, is with lipid AMB formulations, as these agents have lower nephrotoxicity and infusion related toxicity. Residual cavitary lesions, especially those containing fungus balls, after successful antifungal therapy may cause late exsanguinating hemorrhage or reactivation of infection during subsequent myelosuppressive chemotherapy. Advancements in early diagnosis by CT and the introduction of effective agents have improved response rates of primary antifungal therapy.