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在新型隐球菌性脑膜炎小鼠模型中体外唑类药敏性与体内反应的相关性

Correlation of in vitro azole susceptibility with in vivo response in a murine model of cryptococcal meningitis.

作者信息

Velez J D, Allendoerfer R, Luther M, Rinaldi M G, Graybill J R

机构信息

Department of Medicine, University of Texas Health Science Center, San Antonio.

出版信息

J Infect Dis. 1993 Aug;168(2):508-10. doi: 10.1093/infdis/168.2.508.

DOI:10.1093/infdis/168.2.508
PMID:8335995
Abstract

Correlations between in vitro susceptibility and in vivo responses to fluconazole were sought in a mouse model of cryptococcal meningitis. Twenty clinical isolates were used. Two distinct populations were noted. Eight high-virulence isolates had an LD50 of < or = 252 cfu of Cryptococcus neoformans. Twelve low-virulence isolates had an LD50 of > 252 cfu. For 7 low-virulence isolates, the LD50 was > 20,000 cfu. C. neoformans also had a broad range of in vitro susceptibilities (MICs of 1.25 to > 80 micrograms/mL) at 24 h. A correlation was found between the MIC and the minimum effective dose of fluconazole in mice. This was observed with both survival and tissue counts as parameters of efficacy. This study documents for the first time the in vivo relevance of in vitro susceptibility to an azole antifungal for C. neoformans.

摘要

在新型隐球菌性脑膜炎小鼠模型中,研究了氟康唑体外敏感性与体内反应之间的相关性。使用了20株临床分离株。观察到两个不同的群体。8株高毒力分离株的半数致死剂量(LD50)≤252个新型隐球菌集落形成单位(cfu)。12株低毒力分离株的LD50>252 cfu。对于7株低毒力分离株,LD50>20,000 cfu。新型隐球菌在24小时时也具有广泛的体外敏感性(最低抑菌浓度[MIC]为1.25至>80微克/毫升)。在小鼠中发现MIC与氟康唑的最小有效剂量之间存在相关性。以生存和组织计数作为疗效参数时均观察到这种相关性。本研究首次证明了新型隐球菌体外对唑类抗真菌药敏感性的体内相关性。

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