Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis. Cryptococcosis is an emerging infection commonly involving the lungs, from which it can disseminate to different tissues, usually the central nervous system (CNS) (20, 23). Cryptococ-cus neoformans and Cryptococcus gattii are the main agents responsible for this disease, which can affect both immunosup-pressed and healthy individuals. Despite antifungal therapies, this infection still has mortality rates near 20 % (20)