Experimental Trichosporon infection in persistently granulocytopenic rabbits: implications for pathogenesis, diagnosis, and treatment of an emerging opportunistic mycosis.
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.
Walsh
T J
TJ
Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Lee
J W
JW
Melcher
G P
GP
Navarro
E
E
Bacher
J
J
Callender
D
D
Reed
K D
KD
Wu
T
T
Lopez-Berestein
G
G
Pizzo
P A
PA
D000380:Agranulocytosis / Q000150:complications*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D000946:Antigens, Fungal / Q000097:blood; D002825:Chorioretinitis / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D002829:Choroid / Q000382:microbiology; D003881:Dermatomycoses / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D004064:Digestive System / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005767:Gastrointestinal Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D016867:Immunocompromised Host; D007165:Immunosuppression Therapy; D007668:Kidney / Q000382:microbiology; D007674:Kidney Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008168:Lung / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D016253:Microscopy, Immunoelectron; D009181:Mycoses / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D009894:Opportunistic Infections / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D011817:Rabbits; D012867:Skin / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D014250:Trichosporon / Q000276:immunology / Q000648:ultrastructure
D000935:Antifungal Agents; D000946:Antigens, Fungal