Persistent or recurrent unexplained
fever in neutropenic patients receiving
antibiotics can be caused by
invasive fungal infections, which are often difficult to diagnose. Early trials of empirical antifungal
therapy with
amphotericin B deoxycholate (AmB) documented reductions in the frequency of and the morbidity and mortality associated with
invasive fungal infections. Because of AmB's infusional and renal toxicities, subsequent trials used newer, less toxic agents, such as the
lipid formulations of AmB, the extended-spectrum
azoles, and, more recently, the
echinocandins. To date, alternatives to AmB have shown less toxicity, but improved efficacy has been less clear. Overall, empirical antifungal
therapy can help prevent the morbidity associated with many
fungal infections, eliminate concerns about diagnostic pitfalls, and prevent breakthrough undetected
infections. However, its potential shortcomings are overtreatment, toxicity, and increased treatment-related costs when treatment is given to persons not needing it. Newer diagnostic tools are needed to target those most in need of antifungal
therapy.