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伊曲康唑在体外对念珠菌属分离株具有高度活性,但表现出滞后效应。

Isavuconazole is highly active in vitro against Candida species isolates but shows trailing effect.

机构信息

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación, Sanitaria Gregorio Marañón, Madrid, Spain.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación, Sanitaria Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias-CIBERES (CD06/06/0058), Madrid, Spain.

出版信息

Clin Microbiol Infect. 2018 Dec;24(12):1343.e1-1343.e4. doi: 10.1016/j.cmi.2018.07.006. Epub 2018 Jul 17.

DOI:10.1016/j.cmi.2018.07.006
PMID:30025834
Abstract

OBJECTIVES

Isavuconazole is a triazole previously shown to have potent in vitro activity against Aspergillus spp., Mucorales and Candida spp. Unlike other azoles, it is unclear whether isavuconazole induces a trailing effect. We studied isavuconazole MICs for a large collection of Candida isolates from blood samples and determined the extent of the trailing effect when using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.Def 7.3.1 method.

METHODS

A total of 762 molecularly identified Candida isolates from blood samples of 743 patients admitted to hospital (January 2007 to September 2017) were evaluated and further tested for in vitro susceptibility to isavuconazole following the EUCAST E.Def 7.3.1 test method.

RESULTS

C. albicans showed the highest susceptibility, followed by C. parapsilosis and C. tropicalis (geometric mean MIC 0.0029 vs. 0.0049/0.0052, respectively; p <0.001). In contrast, C. glabrata and C. krusei had significantly higher MIC values (geometric mean MIC 0.171 vs. 0.117, respectively). Isavuconazole MIC distributions were not truncated at the lowest concentration tested except for C. albicans. Overall, the mean percentage of trailing was 13.6%, but differences among species were observed: C. glabrata, C. albicans and C. tropicalis exhibited higher trailing compared to C. parapsilosis and non-Candida yeasts (p <0.001). The percentage of non-wild-type C. albicans (considering the heavy trailer isolates as wild type), C. parapsilosis and C. glabrata isolates were 1.1% (4/357), 1.5% (3/201) and 1.1% (1/86), respectively.

CONCLUSIONS

Isavuconazole showed high in vitro activity against Candida spp., particularly against C. albicans. A trailing effect is commonly observed with isavuconazole, particularly with C. glabrata.

摘要

目的

伊曲康唑具有很强的抗曲霉菌属、毛霉菌属和念珠菌属的体外活性。与其他唑类药物不同,其是否存在拖尾效应尚不清楚。我们研究了来自 743 名住院患者血液样本的大量念珠菌分离株的伊曲康唑 MIC,并采用欧洲抗菌药物敏感性试验委员会(EUCAST)E.Def 7.3.1 方法确定拖尾效应的程度。

方法

评估了 2007 年 1 月至 2017 年 9 月期间住院的 743 名患者血液样本中分离的 762 株分子鉴定的念珠菌,并采用 EUCAST E.Def 7.3.1 试验方法进一步检测这些分离株对伊曲康唑的体外敏感性。

结果

白色念珠菌的敏感性最高,其次是近平滑念珠菌和热带念珠菌(几何平均 MIC 分别为 0.0029 和 0.0049/0.0052,P<0.001)。相比之下,光滑念珠菌和克柔念珠菌的 MIC 值明显较高(几何平均 MIC 分别为 0.171 和 0.117)。除白色念珠菌外,伊曲康唑 MIC 分布在最低检测浓度处未截断。总的来说,平均拖尾百分比为 13.6%,但不同种属间存在差异:与近平滑念珠菌和非念珠菌酵母相比,光滑念珠菌、白色念珠菌和热带念珠菌的拖尾现象更为明显(P<0.001)。非野生型白色念珠菌(将重拖尾株视为野生型)、近平滑念珠菌和光滑念珠菌的分离株比例分别为 1.1%(4/357)、1.5%(3/201)和 1.1%(1/86)。

结论

伊曲康唑对念珠菌属具有很强的体外活性,尤其是对白色念珠菌。伊曲康唑通常存在拖尾效应,特别是对光滑念珠菌。

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