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논문 상세정보

Empirical Antifungal Therapy in Febrile Neutropenic Patients

Abstract

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-beta-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.

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