Development of an orogastrointestinal mucosal model of candidiasis with dissemination to visceral organs
Development of an orogastrointestinal mucosal model of candidiasis with dissemination to visceral organs
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DOI：
10.1128/aac.00530-06
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发表时间：
2006-08-01
影响因子：
4.9
通讯作者：
Stevens, David A.
中科院分区：
文献类型：
--
作者：
Clemons, Karl V.;Gonzalez, Gloria M.;Stevens, David A.
进行了研究以开发模拟给予细胞毒性化疗的患者中观察到的粘膜念珠菌病随后播散性疾病的模式的鼠模型。发育研究表明，在感染前3天开始用5-氟尿嘧啶抑制小鼠，此后每7天给药一次，需要进行抗菌治疗，但产生了可重现的模型。在饮用水中给予的白色念珠菌导致第3天的口腔感染，从第10天到第15天显著增加，并且在食道、胃、小肠和盲肠中粘膜感染有4到7个对数级念珠菌CFU。在第5 - 15天发生了肝脏传播，传播率为100%;肾脏感染的动物较少。在第15天，肾脏或肝脏CFU的中位数分别为2或3 log CFU;尽管如此，感染21天内的死亡率很低。作为该模型测试抗真菌活性的实用性的证明，与对照相比，每日用10或50 mg/kg伊曲康唑治疗显著减少了向肝脏和肾脏的传播，并减少了舌CFU。总之，这些研究表明，口腔和胃肠道粘膜念珠菌病的非致死性模型与传播可以建立在小鼠中。可以研究治疗局部感染以及预防或治疗传播性感染的药物功效。
Studies were done to develop a murine model that mimics the pattern of mucosal candidiasis followed by disseminated disease seen in patients given cytotoxic chemotherapy. Developmental studies showed that suppression of mice with 5-fluorouracil beginning 3 days prior to infection and given every 7 days thereafter necessitated antibacterial treatment but resulted in a reproducible model. Candida albicans given in the drinking water resulted in oral infection by day 3 that significantly increased from days 10 to 15 and mucosal infection with 4 to 7 log,, Candida CFU in the esophagus, stomach, small intestine, and cecum. Dissemination to livers occurred and was 100% on days 5 to 15; fewer animals had kidney infection. The median kidney or liver CFU were 2 or 3 log,, CFU, respectively, on day 15; despite this, mortality was low through 21 days of infection. As a demonstration of the utility of the model to test antifungal activity, daily treatment with 10 or 50 mg/kg itraconazole significantly reduced dissemination to the liver and kidneys and reduced tongue CFU compared to controls. Overall, these studies indicate that a nonlethal model of oral and gastrointestinal mucosal candidiasis with dissemination can be established in mice. Drug efficacy in treating localized infection and in preventing or treating disseminated infection can be studied.