Antifungal attributes of immunosuppressive agents: new paradigms in management and elucidating the pathophysiologic basis of opportunistic mycoses in organ transplant recipients.
The currently available immunosuppressive agents cyclosporine A, tacrolimus, and rapamycin have potent antifungal activity against a number of opportunistic fungi in organ transplant recipients, most notably, C. neoformans, Candida, and Aspergillus species. The targets of their antifungal activity are fungal homologs of the signaling molecules that mediate their immunosuppressive action in humans, which has implications for further unraveling the pathogenesis of these infections. Corroborative clinical data suggest that despite the apparent paradox between the antifungal activity of the immunosuppressive agents and the occurrence of fungal infections during their administration, the antifungal attributes of these drugs may influence the spectrum and clinical characteristics of these infections after organ transplantation. Finally, the potent synergistic interactions between the immunosuppressive agents and antifungal drugs against many pathogenic fungi, including those that are typically resistant to traditional antifungal agents, could potentially have a role in devising novel therapeutic strategies for opportunistic mycoses in transplant recipients.
Singh
Nina
N
University of Pittsburgh Medical Center, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA. nis5+@pitt.edu
Heitman
Joseph
J
D000935:Antifungal Agents / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009181:Mycoses / Q000188:drug therapy / Q000503:physiopathology*; D009894:Opportunistic Infections / Q000188:drug therapy* / Q000209:etiology; D014180:Transplantation
D000935:Antifungal Agents; D007166:Immunosuppressive Agents