Experimental Trichosporon Infection in Persistently Granulocytopenic Rabbits: Implications for Pathogenesis, Diagnosis, and Treatment of an Emerging Opportunistic Mycosis

Abstract

Disseminated Trichosporon infection, an uncommon but emerging opportunistic mycosis due to Trichosporon beigelii, is frequently difficult to diagnose, refractory to treatment, and associated with a high attributable mortality. Models of disseminated and gastrointestinal Trichosporon infection were developed in persistently granulocytopenic rabbits. The patterns of infection resembled those of clinical disease, including cutaneous lesions, chorioretinitis, renal infection, pulmonary infection, and antigenemia cross-reactive with cryptococcal capsular polysaccharide. Antigenemia, an early manifestation of disseminated Trichosporon infection, originated in vivo from a fibrillar extracellular matrix. Trichosporon organisms disseminated from the gastrointestinal tract to visceral tissue in colonized immunosuppressed rabbits, whereas there was no dissemination from the gastrointestinal tract of otherwise normal rabbits. The antifungal triazoles, fluconazole and SCH 39304, were most active; maximum tolerated doses of amphotericin B and liposomal amphotericin B were ineffective. Trichosporon antigenemia declined in response to antifungal therapy. These findings contribute to improved understanding of the pathogenesis, diagnosis, and treatment of disseminated Trichosporon infection.

Invasive Infections Caused byTrichosporonSpecies andGeotrichum capitatumin Patients with Hematological Malignancies: a Retrospective Multicenter Study from Italy and Review of the Literature

“…strains isolated from neutropenic patients with disseminated trichosporonosis that was refractory to this drug (127). Several groups have demonstrated the in vitro activity of azole antifungals against members of the Trichosporon genus, and these drugs have produced favorable responses in animal models (4,5,126,127). However, relatively high fluconazole MICs have been found for some Trichosporon isolates (121,122), and multidrug resistance to amphotericin B, flucytosine, fluconazole, and itraconazole has also been reported (131).…”

Increased release of glucuronoxylomannan antigen and induced phenotypic changes in Trichosporon asahii by repeated passage in mice

“…neoformans [19]. GXM antigen is localised to the cell wall and to fibrillar extracellular matrix projecting from the cell wall of T. beigelii [20,21]. The significantly higher GXM antigen titre in clinical isolates relative to that in environmental isolates is likely to be due to a higher release of GXM antigen from the organisms, as it cannot simply be explained by differences in the cell surface area.…”

Testing Conditions for Determination of Minimum Fungicidal Concentrations of New and Established Antifungal Agents for Aspergillus spp.: NCCLS Collaborative Study

“…Whether MICs are the best in vitro predictors of in vivo or clinical response to antifungal therapy is uncertain. Although standard conditions are not available for determination of fungicidal activities for either yeasts or moulds, it has been demonstrated that MFCs may be better predictors than MICs of therapeutic failure of amphotericin B in trichosporonosis (26,27) and candidemia (20). The fungicidal activities of the new triazoles have also been evaluated during the last few years by nonstandardized methods (3,7,11,13,14,16,17,21,24,25).…”