In vitro activity of immunosuppressive agents against Cryptococcus neoformans / Actividad in vitro de agentes inmunosupresores frente a Cryptococcus neoformans

ABSTRACT

IntroductionInfections 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.MethodsMICs 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.ResultsIntroductionInfections 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.MethodsMICs 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.ResultsTacrolimus 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.ConclusionsThe 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.

RESUMEN

IntroducciónLas infecciones causadas por Cryptococcus neoformans son la principal causa de mortalidad por hongos en pacientes con infección por el VIH/SIDA o en pacientes trasplantados. Evaluamos la actividad in vitro de tacrolimus y ciclosporina A en combinación con anfotericina B y fluconazol frente a C. neoformans.MétodosSe determinaron las CMI de ciclosporina A y tacrolimus frente a 30 aislados clínicos de C. neoformans mediante microdilución, según el documento CLSI M27-A3 y por el método del tablero de ajedrez.ResultadosTacrolimus y ciclosporina A mostraron actividad in vitro frente a C. neoformans. La combinación de anfotericina B con ciclosporina A o tacrolimus fue sinérgica frente al 90 y 30% de aislados, respectivamente. Se observó sinergismo con fluconazol y ciclosporina A o tacrolimus, frente al 70 y 20% de aislados, respectivamente.ConclusionesLa actividad sinérgica entre inhibidores de la calcineurina y antimicóticos frente a C. neoformans podría ser una nueva estrategia terapéutica para esta micosis.