In vitro activity of immunosuppressive agents against Cryptococcus neoformans.

Infections caused by Cryptococcus neoformans are a major cause of fungal mortality in HIV-infected/AIDS patients and in those receiving organ transplants. We evaluated the in vitro activity of tacrolimus and cyclosporine in combination with amphotericin B and fluconazole against C. neoformans. MICs were determined against a total of 30 clinical isolates of C. neoformans by the microdilution method following the CLSI M27-A3 guidelines and by the checkerboard method. Tacrolimus and cyclosporine A showed in vitro activity against cryptococcal isolates. The combination of amphotericin B with cyclosporine A or tacrolimus was synergistic against 90% and 30% of isolates, respectively. Synergism was also observed with the combination of fluconazole with cyclosporine A or tacrolimus, against 70% and 20% of isolates, respectively. The synergistic interactions between the calcineurin inhibitors and antifungal drugs against C. neoformans isolates, could potentially have a role in devising novel therapeutic strategies for this opportunistic mycosis.

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