Clinical perspectives on echinocandin resistance among Candida species.
Clinical perspectives on echinocandin resistance among Candida species.
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DOI：
10.1097/qco.0000000000000215
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发表时间：
2015-12
影响因子：
3.9
通讯作者：
Clancy CJ
中科院分区：
文献类型：
--
作者：
Shields RK;Nguyen MH;Clancy CJ
我们回顾并提供我们的临床观点对棘白菌素耐药念珠菌的出现。假丝酵母FKS基因突变会减弱棘球珠素的活性，但临床分离株的总体突变率仍然很低（C. glabrata，约4%；其他物种，<1%）。先前接触棘球珠菌素的比例更高，超过50%的裸纹念珠菌或白色念珠菌分离株导致突破性侵袭性念珠菌病。在FKS突变株中，先前接触棘白菌素的中位持续时间为~ 100天。棘白菌素药敏检测的临床应用受到总体耐药率低、检测方法和最低抑菌浓度（mic）解释的不确定性的限制。在单中心研究中，caspofunins耐药（使用机构特异性MIC断点定义）在预测光秃梭菌侵袭性念珠菌病治疗结果方面的敏感性为32-53%，特异性为75-95%；FKS突变存在的对应值分别为35-41%和90-98%。阿尼杜弗宁和米卡弗宁mic的结果相似。非c型的临床资料很少。glabrata物种。棘白菌素仍然是抗侵袭性念珠菌感染的首选药物。药敏试验和FKS基因型试验在常规临床实践中没有作用，但可能对新诊断的棘白菌素经验或对棘白菌素治疗无反应的患者有用。
We review and offer our clinical perspectives on the emergence of echinocandin-resistant Candida. Candida FKS gene mutations attenuate echinocandin activity, but overall mutation rates among clinical isolates remain low (C. glabrata, ∼4%; other species, <1%). Rates are higher with prior echinocandin exposure, exceeding 50% among C. glabrata or C. albicans isolates causing breakthrough invasive candidiasis. The median duration of prior echinocandin exposure among FKS mutant isolates is ∼100 days. The clinical usefulness of echinocandin susceptibility testing is limited by the low overall prevalence of resistance, and uncertainties surrounding testing methods and interpretation of minimum inhibitory concentrations (MICs). In single-center studies, caspofungin resistance (defined using institution-specific MIC breakpoints) was 32-53% sensitive and 75-95% specific for predicting treatment outcomes of C. glabrata invasive candidiasis; corresponding values for the presence of an FKS mutation were 35-41% and 90-98%. Results were similar using anidulafungin and micafungin MICs. Clinical data are scarce for non-C. glabrata species. Echinocandins remain preferred agents against invasive Candida infections. Susceptibility testing and FKS genotypic testing do not have roles in routine clinical practice, but may be useful in newly-diagnosed patients who are echinocandin-experienced or those who have not responded to echinocandin treatment.