Breakthrough Aspergillus fumigatus and Candida albicans Double Infection during Caspofungin Treatment: Laboratory Characteristics and Implication for Susceptibility Testing
Breakthrough Aspergillus fumigatus and Candida albicans Double Infection during Caspofungin Treatment: Laboratory Characteristics and Implication for Susceptibility Testing
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DOI：
10.1128/aac.01292-08
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发表时间：
2009-03-01
影响因子：
4.9
通讯作者：
Bruun, Brita
中科院分区：
文献类型：
--
作者：
Arendrup, Maiken Cavling;Garcia-Effron, Guillermo;Bruun, Brita
卡泊芬净用于治疗急性侵袭性念珠菌病和侵袭性曲霉病的挽救治疗。我们报告了在严重胃肠道手术并发突破性感染患者中检测到的白色念珠菌和烟曲霉分离株的特征，并评估了敏感性方法鉴定念珠菌耐药性的能力。C.通过Etest、微量稀释（欧洲抗生素敏感性试验委员会[ EUCAST]和CLSI）、纸片扩散、琼脂稀释和FKS 1测序以及在小鼠模型中研究了白色念珠菌对卡泊芬净和阿尼芬净的耐受性。通过免疫组织化学、PCR和测序检测组织中是否存在A。烟曲霉和抗性突变。C的MIC。白色念珠菌分离株的结果如下：Etest法> 32 μ g/ml卡泊芬净和0.5 μ g/ml阿尼芬净，EUCAST法> 2 μ g/ml卡泊芬净和0.125 μ g/ml阿尼芬净，CLSI法> 1 μ g/ml卡泊芬净和0.5 μ g/ml阿尼芬净。FKS 1基因的测序揭示了导致S645 P取代的突变。卡泊芬净和阿尼芬净不能降低接种该分离株的动物的肾脏CFU计数（与未处理的对照动物相比P > 0.05），而两种candin都能完全杀灭感染对照分离株的动物的肾脏。纸片扩散法和琼脂稀释法可将两株分离株明显分离。免疫组化和测序证实了A.在肝和肺组织中没有FSK 1抗性突变的烟曲霉。突破性播散性曲霉病和念珠菌病的发展，尽管缺乏特征性FKS 1耐药突变的曲霉菌菌株。EUCAST和CLSI方法以及Etest和琼脂方法未将candin耐药临床分离株与敏感对照分离株分开。
Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery and evaluate the capability of susceptibility methods to identify candin resistance. The susceptibility of C. albicans to caspofungin and anidulafungin was investigated by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing [ EUCAST] and CLSI), disk diffusion, agar dilution, and FKS1 sequencing and in a mouse model. Tissue was examined by immunohistochemistry, PCR, and sequencing for the presence of A. fumigatus and resistance mutations. The MICs for the C. albicans isolate were as follows: > 32 mu g/ml caspofungin and 0.5 mu g/ml anidulafungin by Etest, 2 mu g/ml caspofungin and 0.125 mu g/ml anidulafungin by EUCAST methods, and 1 mu g/ml caspofungin and 0.5 mu g/ml anidulafungin by CLSI methods. Sequencing of the FKS1 gene revealed a mutation leading to an S645P substitution. Caspofungin and anidulafungin failed to reduce kidney CFU counts in animals inoculated with this isolate (P > 0.05 compared to untreated control animals), while both candins completely sterilized the kidneys in animals infected with a control isolate. Disk diffusion and agar dilution methods clearly separated the two isolates. Immunohistochemistry and sequencing confirmed the presence of A. fumigatus without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from the sensitive control isolate as well as did the Etest and agar methods.