Cole G T, Lynn K T, Seshan K R
Department of Botany, University of Texas, Austin 78713-7640.
J Clin Microbiol. 1990 Aug;28(8):1828-41. doi: 10.1128/jcm.28.8.1828-1841.1990.
A murine model of focal hepatic candidiasis which we suggest simulates certain conditions of this clinical variant of systemic candidiasis in leukemic patients is described. We have shown that outbred mice inoculated with Candida albicans by the oral-intragastric route as infants (6 days old) and then immunocompromised by cyclophosphamide and cortisone acetate treatment 2 weeks later demonstrate systemic spread of the opportunistic pathogen to the liver, lungs, spleen, and kidneys. Treatment with the immunosuppressive drugs cyclophosphamide and cortisone acetate resulted in alteration of the normal integrity of the mucosal epithelium of the gut as well as in granulocytopenia. Approximately 55% of the animals with C. albicans infections in the liver demonstrated hepatic abscesses. After these same infected, immunocompromised animals were treated with suboptimal dosages of antifungal agents (cilofungin or amphotericin B), either by intraperitoneal or subcutaneous (s.c.) routes, persistent hepatic abscesses were fewer in number and delimited by a distinct outer layer of host tissue but still contained large numbers of the viable pathogen. Blood cell counts indicated that these antifungal drug-treated animals had reestablished approximately the same number of leukocytes per microliter of blood as estimated prior to the immunocompromising drug treatment. Similar conditions in leukemic patients who were in remission and who were undergoing antifungal drug therapy for systemic candidiasis have been reported. Clearance of hepatic infections in mice was accomplished by using appropriate concentrations of amphotericin B administered by daily intraperitoneal or s.c. injection for 5 to 7 days or cilofungin by continuous s.c. infusion for 7 days. However, systemic antifungal therapy did not significantly reduce numbers of C. albicans cells in the stomach and esophagus. Persistent foci of gastrointestinal colonization by C. albicans, especially in the region of the cardial-atrium fold of the stomach of these mice, are reservoirs of the opportunistic pathogen from which reinfection may occur, leading to relapse of systemic candidiasis.
本文描述了一种局灶性肝念珠菌病的小鼠模型，我们认为该模型模拟了白血病患者系统性念珠菌病这一临床变体的某些情况。我们已经表明，幼年（6日龄）经口 - 胃内途径接种白色念珠菌，然后在2周后通过环磷酰胺和醋酸可的松治疗使其免疫受损的远交系小鼠，显示机会性病原体系统性扩散至肝脏、肺、脾和肾脏。免疫抑制药物环磷酰胺和醋酸可的松治疗导致肠道黏膜上皮正常完整性改变以及粒细胞减少。肝脏感染白色念珠菌的动物中约55%出现肝脓肿。这些相同的感染且免疫受损的动物经腹腔内或皮下途径用次优剂量的抗真菌药物（西洛芬净或两性霉素B）治疗后，持续性肝脓肿数量减少，被一层明显的宿主组织外层所界定，但仍含有大量活的病原体。血细胞计数表明，这些接受抗真菌药物治疗的动物每微升血液中重新建立的白细胞数量与免疫抑制药物治疗前估计的数量大致相同。已有报道称，处于缓解期且正在接受系统性念珠菌病抗真菌药物治疗的白血病患者也有类似情况。通过每日腹腔内或皮下注射适当浓度的两性霉素B持续5至7天，或通过皮下连续输注西洛芬净7天，可实现小鼠肝脏感染的清除。然而，全身抗真菌治疗并未显著减少胃和食管中白色念珠菌细胞的数量。白色念珠菌在胃肠道的持续定植灶，尤其是这些小鼠胃贲门 - 心房褶区域，是机会性病原体的储存库，可能由此发生再感染，导致系统性念珠菌病复发。
