Anaissie E, Hachem R, K-Tin-U C, Stephens L C, Bodey G P
Department of Medical Specialties, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Infect Immun. 1993 Apr;61(4):1268-71. doi: 10.1128/iai.61.4.1268-1271.1993.
Hematogenous infections caused by Candida krusei have been noted with increasing frequency, particularly in cancer patients receiving prophylaxis with antifungal triazoles. Progress in understanding the pathogenesis of this emerging infection has been limited by the lack of an animal model. We developed a CF1 mouse intravenous inoculation model of candidiasis to evaluate the pathogenicity of C. krusei in normal and immunosuppressed mice and to compare it with that of Candida albicans. Several inocula (10(6) to 10(8) CFU per animal) of two clinical strains of C. krusei and three American Type Culture Collection strains of C. albicans were tested. Groups of 20 mice each were injected with a single intravenous dose of one inoculum. Animals randomized to receive C. krusei were immunosuppressed by intraperitoneal injection of cyclophosphamide or the combination of cyclophosphamide plus cortisone acetate or they did not receive immunosuppressive agents (normal mice). One hundred percent mortality was observed in normal mice injected with 10(6) CFU of C. albicans per mouse compared with no mortality in normal mice that received 10(8) CFU of C. krusei per mouse (P < 0.01). Resistance to C. krusei infection was markedly lowered by immunosuppression, particularly by the combination of cyclophosphamide plus cortisone acetate, with a significantly shorter survival and a higher organ fungal burden in immunosuppressed than in normal animals (P < 0.01). Tissue infection was documented by culture and histopathologic findings in all examined organs.
克鲁斯念珠菌引起的血源性感染日益常见,尤其是在接受抗真菌三唑类药物预防治疗的癌症患者中。由于缺乏动物模型,对这种新出现感染的发病机制的了解进展有限。我们建立了一种CF1小鼠念珠菌病静脉接种模型,以评估克鲁斯念珠菌在正常和免疫抑制小鼠中的致病性,并将其与白色念珠菌进行比较。对克鲁斯念珠菌的两个临床菌株和白色念珠菌的三个美国典型培养物保藏中心菌株的几种接种量(每只动物10⁶至10⁸CFU)进行了测试。每组20只小鼠,每只静脉注射一剂接种物。随机接受克鲁斯念珠菌的动物通过腹腔注射环磷酰胺或环磷酰胺加醋酸可的松进行免疫抑制,或者不接受免疫抑制剂(正常小鼠)。每只小鼠注射10⁶CFU白色念珠菌的正常小鼠全部死亡,而每只小鼠注射10⁸CFU克鲁斯念珠菌的正常小鼠无一死亡(P<0.01)。免疫抑制显著降低了对克鲁斯念珠菌感染的抵抗力,尤其是环磷酰胺加醋酸可的松联合使用时,免疫抑制动物的存活时间明显缩短,器官真菌负荷高于正常动物(P<0.01)。通过培养和组织病理学检查在所有检查的器官中均证实了组织感染。