The use of itraconazole as prophylaxis against invasive fungal infection in blood and marrow transplant recipients.

Abstract

Invasive fungal infections play a key role in contributing to morbidity and mortality in patients undergoing treatment for haematological malignancies and related diseases. Risk factors for development of invasive fungal infections after blood or bone marrow transplantation include the use of broad-spectrum antibiotics, steroids, mismatched or unrelated donor transplant, right atrial catheters, and prolonged or profound neutropenia. Previous attempts at use of oral itraconazole as antifungal prophylaxis in the setting of chemotherapy-induced neutropenia were unsuccessful because of its poor absorption in capsule form. Itraconazole-cyclodextrin is well absorbed even in the presence of chemotherapy-induced neutropenia. Plasma levels of 250-500 ng/ml are required for prophylaxis. Studies to date show a favourable outcome in patients receiving itraconazole as prophylaxis against invasive fungal infections, although many studies looked at small numbers of patients and the incidence of invasive fungal infection in the control groups was low, prohibiting meaningful statistical evaluation. Fungi differ in their sensitivity to antifungal agents, and itraconazole is not the agent of choice in all patients. With the widespread use of antifungal prophylaxis, the possibility of resistance to antifungal agents and an increase in the number of invasive fungal infections caused by ubiquitous fungi previously considered nonpathogenic must be considered as potential problems.