Life-threatening disseminated
infection with Trichosporon beigelii (
trichosporonosis) is a rare mycosis most commonly seen in patients with
hematologic malignancies made neutropenic by cytotoxic
therapy. This
infection is usually resistant to conventional antifungal
therapies. Poor correlation between therapeutic outcome of
trichosporonosis and in vitro susceptibility of clinical isolates of T. beigelii to
antifungal agents is often reported. To obtain a better understanding of its pathogenesis, and to aid in the future study of the
therapy of this disease, a murine model of
trichosporonosis was developed. The in vitro growth of clinical isolates of T. beigelii was first studied. Subsequently, mice made neutropenic with
cyclophosphamide were inoculated intravenously with the fungus to produce the disease model. Inoculum size which produced 100% mortality, yet allowed an apparent therapeutic window (6 x 10(6)) was determined. Tissue distribution and burden of organism during the course of
infection was examined by viability and histopathologic studies. T. beigelii disseminated rapidly in this model, involving numerous organs including the heart, brain, kidneys, lungs, and liver. The heart and kidneys of the infected animals showed evidence of
infection as early
as 6 hours following inoculation. Further understanding of the pathogenesis of
trichosporonosis in the neutropenic host was imparted by this study. This will aid in the future study of
antibiotic treatment of this disease and its untreated progression.