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Chapter 39 : Antifungal Trials: Progress, Approaches, New Targets, and Perspectives in Cryptococcosis

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Abstract:

This chapter briefly describes the history of treatment for CNS cryptococcosis and discusses novel approaches to therapy with traditional agents, the newer antifungal agents, experimental agents, and the potential role of immunotherapy. The availability of fluconazole, itraconazole, the lipid formulations of amphotericin B, and the expanded spectrum triazoles provided additional options in the antifungal armamentarium. There are several newer antifungal agents that could offer significant advantages over more traditional agents. Specifically, three new triazoles, voriconazole, posaconazole, and isavuconazole, demonstrate excellent in vitro activity against most strains of clinically relevant species. Passive immunotherapy has been advocated as a potentially important adjunct to conventional antifungal therapy in the management of invasive mycoses. The hypothetical value of cryptococcal antigen removal from the infected host relates to its function as a virulence factor: cryptococcal antigen is known to inhibit leukocyte migration, promote cerebral edema, promote cytokine dysregulation, induce T-lymphocyte secretion of immunosuppressive molecules, and induce the shedding of L-selectin. There are good data supporting the role of adjuvant corticosteroids in the early management of bacterial meningitis, and this has become a standard approach to patients with proven or suspected disease. Tacrolimus demonstrates synergistic activity with several antifungals including bafilomycin A (an experimental agent), caspofungin, and fluconazole. In the developed world, cryptococcosis in transplantation represents a large and inadequately studied complication among transplant recipients.

Citation: Pappas P. 2011. Antifungal Trials: Progress, Approaches, New Targets, and Perspectives in Cryptococcosis, p 527-536. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch39

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