Fatal systemic candidiasis of gastrointestinal origin: an experimental model in mice compromised by anti-cancer treatment.
An experimental model of fatal systemic candidiasis originating from the gastrointestinal (GI) tract of compromised mice is presented. ICR female mice were compromised by a single anti-cancer treatment: irradiation (4 or 6 Greys i.e. 400-600 rads), methotrexate (MTX) (3 mg per mouse, intraperitoneally) or 5-fluorouracil (5FU) (200 mg kg-1, intravenously). Three days later, compromised and non-treated control mice were exposed to Candida albicans administered orally. Morbidity and mortality due to candidiasis were monitored for 30 days post-candidal inoculation. Increased and longer GI colonization was noted among the MTX and 5FU treated mice, or 6 Greys irradiated mice (up to 92.3% for over 30 days in anti-cancer treated mice). The stomach was found to be the major part of the GI tract involved in fungal colonization. A significant number (53.8-83.3%) of the anti-cancer treated mice developed systemic candidiasis originating from the GI tract, which was fatal in 30-80% of the infected animals. In systemically infected animals, candidal antigen was demonstrated in the serum, and fungal abscesses containing C. albicans were observed in the liver, kidneys and spleen. C. albicans was isolated from the infected organs. The severity of the infection, as reflected by the number of fungi in visceral organs, and by mortality during the 30 days post-candidal inoculation, indicated differences in the course and nature of the infection among the three treatment groups (i.e. MTX, 5FU, 6 Greys).(ABSTRACT TRUNCATED AT 250 WORDS)
Sandovsky-Losica
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Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Israel.
Barr-Nea
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Segal
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D000818:Animals; D002176:Candida albicans / Q000254:growth & development*; D002177:Candidiasis / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D002432:Cecum / Q000382:microbiology; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D004947:Esophagus / Q000382:microbiology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D016867:Immunocompromised Host; D007422:Intestines / Q000382:microbiology; D008099:Liver / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D014781:Viscera / Q000473:pathology
D005472:Fluorouracil; D008727:Methotrexate