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实验性白色念珠菌性骨髓炎:在新建立的兔模型中的微生物学、抗原性、组织学和 18FDG-PET-CT 成像特征。

Experimental Candida albicans osteomyelitis: Microbiologic, antigenic, histologic, and 18FDG-PET-CT imaging characteristics in a newly established rabbit model.

机构信息

Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Clinical Microbiology Laboratory, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Med Mycol. 2019 Nov 1;57(8):1011-1017. doi: 10.1093/mmy/myz001.

DOI:10.1093/mmy/myz001
PMID:30753591
Abstract

Candida osteomyelitis is a debilitating disease that is difficult to diagnose and treat. As there are no animal models or prospective studies for this uncommon infection, little is known about the pathogenesis, diagnosis, or treatment. We therefore sought to establish an animal model for the study of the pathophysiology, diagnostic modalities, and therapeutic interventions of Candida osteomyelitis. We developed a modified version of the Norden rabbit model of tibial osteomyelitis, in which the right tibia was inoculated intraoperatively with different inocula of C. albicans or normal saline as control. On days 7, 14, and 21 after inoculation, the animals underwent bone radiography, 18-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET/CT) scan, and blood sampling for blood cultures, blood counts, erythrocyte sedimentation rate, and Candida mannan antigen serum levels. On day 21, animals were euthanized, and infected tibias harvested for culture and histology. Among eight evaluable animals inoculated with 1 × 106 to 1 × 107 cfu, histology and bone cultures established the presence of Candida osteomyelitis in seven, with a host response of neutrophils, mononuclear cells, multinucleate giant cells, fibrosis, and necrosis. Infected animals demonstrated radiological signs of osteomyelitis with significantly increased tracer uptake in 18FDG-PET/CT scans (P < .01) and elevated serum mannan levels (P < .01). All blood cultures were negative. Indices of inflammation were only slightly increased. In conclusion, we report successful establishment of a new animal model of Candida albicans osteomyelitis that may be applicable to advancing our understanding of the pathophysiology, diagnostic modalities, and treatment of this debilitating infection.

摘要

白色念珠菌性骨髓炎是一种难以诊断和治疗的衰弱性疾病。由于这种罕见感染没有动物模型或前瞻性研究,因此对其发病机制、诊断或治疗知之甚少。因此,我们试图建立一种动物模型,以研究白色念珠菌性骨髓炎的病理生理学、诊断方式和治疗干预措施。我们对 Norden 兔胫骨骨髓炎模型进行了改良,术中将不同剂量的白色念珠菌或生理盐水接种于右侧胫骨作为对照。在接种后第 7、14 和 21 天,对动物进行骨放射照相、18-氟-2-脱氧-D-葡萄糖正电子发射断层扫描与计算机断层扫描(PET/CT)扫描以及血液采样,以进行血液培养、血细胞计数、红细胞沉降率和念珠菌甘露聚糖抗原血清水平检测。在第 21 天,处死动物并采集感染胫骨进行培养和组织学检查。在接种 1×106 至 1×107 cfu 的 8 只可评估动物中,7 只动物的组织学和骨培养证实存在白色念珠菌性骨髓炎,其宿主反应为中性粒细胞、单核细胞、多核巨细胞、纤维化和坏死。感染动物的 X 光片显示有骨髓炎的迹象,18FDG-PET/CT 扫描的示踪剂摄取明显增加(P<.01),甘露聚糖血清水平升高(P<.01)。所有血液培养均为阴性。炎症指数仅略有增加。总之,我们成功建立了一种新的白色念珠菌性骨髓炎动物模型,该模型可能适用于深入了解这种衰弱性感染的病理生理学、诊断方式和治疗方法。

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