Antifungal therapy in patients with hematological malignancies: how to avoid overtreatment?

Abstract

Historically, treatment of invasive fungal infections (IFI) has consisted of amphotericin B. However, new therapeutic agents have recently been introduced. At the same time, the relatively low incidence of IFI and the progress in the diagnostic accuracy of IFI have made routine use of empirical antifungal therapy questionable. With the aim to define the present trends in the use of antifungal agents for the treatment of IFI, we prospectively observed type, safety, and efficacy of given antifungal treatment in patients with hematological malignancies during a recent 18-month period. We also analyzed the impact of restricted use of empirical antifungal therapy on IFI-related mortality. A total of 279 episodes of neutropenia and fever following the chemotherapy were recorded. Treatment of IFI was given during the management of 41 (14%) episodes. Voriconazole (27 episodes) and caspofungin (14 episodes) were the only antifungal agents used as initial therapy. The rate of antifungal therapy success outcome was 78%. The overall 4-week mortality rate was 8%. Two patients died of invasive pulmonary aspergillosis. Empirical antifungal therapy was given in 13 episodes with persistent febrile neutropenia (PFN) and resulted in successful outcome in 92% of cases. In general, antifungal agents were well tolerated and only two patients had to discontinue treatment because of severe adverse event. In 127 episodes of PFN, antifungal therapy was deemed unnecessary and accordingly was not administered. In this subgroup of patients, no IFI-related mortality occurred. A better tolerability and efficacy of voriconazole and caspofungin together with the availability of an oral formulation of voriconazole most probably contributed to the observed shift in the use of antifungal agents. A restricted use of empirical antifungal therapy was, in this setting, not associated with an increased IFI-related mortality.