通过在小鼠侵袭性感染中测试具有不同伊曲康唑敏感性的念珠菌菌株，研究伊曲康唑静脉和口服增溶制剂的体外活性与体内疗效的相关性。
Correlation of in vitro activity and in vivo efficacy of itraconazole intravenous and oral solubilized formulations by testing Candida strains with various itraconazole susceptibilities in a murine invasive infection.
机构信息
Teikyo University Institute of Medical Mycology, Hachioji, Tokyo 192-0395, Japan.
出版信息
J Antimicrob Chemother. 2011 Mar;66(3):626-34. doi: 10.1093/jac/dkq475. Epub 2010 Dec 15.
OBJECTIVES
To examine whether in vitro antifungal susceptibility test results correlate with in vivo efficacy of two cyclodextrin-solubilized itraconazole formulations (intravenous and oral) against Candida in a murine model of invasive infection.
METHODS
A selected set of 12 Candida spp. strains with various itraconazole susceptibilities were tested. We studied the efficacy of intravenous and oral itraconazole administered once daily at dosages of 0.63, 2.5, 10 and 40 mg/kg body weight in mice lethally infected with each tested strain. Survival of mice in each treated group was monitored daily until the death of all control mice and compared between groups.
RESULTS
Survival of mice infected with 9 of 12 Candida strains with itraconazole MICs of ≤0.016-2.0 mg/L was significantly prolonged by treatment with intravenous itraconazole at dosages of 2.5 or 10 mg/kg and above. In contrast, the other three strains resistant to 8 mg/L itraconazole in vitro were refractory to the therapy, even at the highest itraconazole dosage (40 mg/kg). Closely similar in vivo data were obtained with the oral itraconazole therapy. The effective doses of the two itraconazole formulations increased with increasing itraconazole MICs for the infecting strains.
CONCLUSIONS
The in vivo efficacy of intravenous and oral itraconazole correlated with the in vitro susceptibility data.
目的
研究两种环糊精增溶伊曲康唑制剂（静脉注射和口服）在侵袭性感染的小鼠模型中对抗白色念珠菌的体外抗真菌药敏试验结果与体内疗效是否相关。
方法
选择了一组具有不同伊曲康唑敏感性的 12 株白色念珠菌菌株进行测试。我们研究了在每个测试菌株致死性感染的小鼠中，每天一次给予静脉注射和口服伊曲康唑，剂量为 0.63、2.5、10 和 40mg/kg 体重的疗效。监测每个治疗组中小鼠的存活情况，直到所有对照小鼠死亡，并在组间进行比较。
结果
用 2.5 或 10mg/kg 及以上剂量的静脉注射伊曲康唑治疗，可显著延长对 9/12 株白色念珠菌菌株的感染小鼠的存活时间，这些菌株的伊曲康唑 MIC 值为 ≤0.016-2.0mg/L。相比之下，另外三株对 8mg/L 伊曲康唑体外耐药的菌株对治疗有抗药性，即使使用最高的伊曲康唑剂量（40mg/kg）也是如此。口服伊曲康唑治疗也获得了类似的体内数据。两种伊曲康唑制剂的有效剂量随着感染菌株的伊曲康唑 MIC 值的增加而增加。
结论
静脉注射和口服伊曲康唑的体内疗效与体外药敏数据相关。
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