Empirical antifungal therapy in febrile neutropenic patients

Invasive fungal infection is an important cause of morbidity and mortality in granulocytopenic patients receiving cancer chemotherapy or undergoing bone marrow or stem-cell transplantation. The most common pathogens are Candida species and Aspergillus species, and other fungi are also encountered. Empirical antifungal therapy with conventional amphotericin B or liposomal amphotericin B has become the standard of care in reducing invasive fungal infections in patients with neutropenia and persistent fever. Amphotericin B is associated with significant dose-limiting nephrotoxicity and infusion-related reactions. Liposomal amphotericin B is equivalent to conventional amphotericin B as empirical antifungal therapy and significantly reduces proven invasive fungal infections, nephrotoxicity, and infusion-related reactions. The high acquisition cost of liposomal amphotericin B, however, has limited the use of this less toxic formulation of amphotericin B. The lipid formulations of amphotericin B and triazoles (fluconazole, itraconazole, voriconazole), were found to be a suitable alternative to amphotericin B preparations as empirical antifungal agents in patients with persistent fever and neutropenia. However, these agents may be associated with toxicity and adverse drug interactions and have a limited spectrum of activity, erratic bioavailability, unpredictable pharmacokinetics, and limited efficacy. Caspofungin is a relatively new class of antifungal agents that non-competitively inhibit the synthesis of fungal cell-wall 1,3-β-D-glucan. Caspofungin is a suitable alternative to liposomal amphotericin B as empirical therapy and offered the advantages of safety, improved survival, and improved response rates in patients with invasive fungal infections. However, caspofungin has a drug interactions with dexamethasone, cyclosporine, tacrolimus and is expensive. Numerous antifungal agents could represent potential alternatives to amphotericin B, a difficult drug to administer. The optimal empiric antifungal therapy remains a matter of controversy. Clinicians ultimately have to select the optimal antifungal agents after considering the cost as well as efficacy, toxicity of the drugs.