Changing Spectrum of C. neoformans Infection in Organ Transplant Recipients in the Era of Calcineurin-Inhibitor Based Immunosuppression (Tacrolimus and Cyclosporine, CsA).


Author address: 

Crypto Collab Transplant Gp.; 1 U.Pitt, Pittsburgh, PA, 2 CMC, Vellore, India


Background: Tacrolimus and CsA have in vitro antifungal activity against C. neoformans at 37°C (but not at lower temperatures) by inhibition of fungal homologs of calcineurin(AAC 97). Whether the spectrum or outcome of cryptococcosis in transplant setting is effected by calcineurin-inhibitors, is not known. Methods: Since 1999, 31 cases of C. neoformans were prospectively identified at 14 transplant centers. Results: Cases included 15 kidney, 10 liver, 4 heart, 1 lung, and 1 kidney-pancreas recipient. All isolates were serotype A except 1, which was serotype B var gatti. Sites involved were: see table Tacrolimus recipients were less likely to have CNS involvement than all other patients(27.8% vs. 81.8%, p = 0.008). 33% of the cases occurred 12 mo. (late onset). Patients receiving tacrolimus (p = 0.004), those with rejection (p = 0.025), and liver transplant recipients (p = 0.045) were significantly more likely to have early-onset infection. 90d mortality did not differ for early (22.2%) vs. late-onset (20%) cases. Conclusions: Calcineurin-inhibitor based immunosuppression appears to influence the spectrum of C. neoformans infection. Patients receiving tacrolimus had earlier onset of infection but were less likely to have CNS infection. Difference in tissue tropism was not related to the serotype involved. Whether CNS penetration, inhibition of fungal calcineurin in tissues at high temperature, e.g. CNS, or other mechanisms account for these observations, remains to be elucidated.

abstract No: 


Full conference title: 

    • ICAAC 42nd