Increasing Echinocandin Resistance in Candida glabrata: Clinical Failure Correlates With Presence of FKS Mutations and Elevated Minimum Inhibitory Concentrations
Increasing Echinocandin Resistance in Candida glabrata: Clinical Failure Correlates With Presence of FKS Mutations and Elevated Minimum Inhibitory Concentrations
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DOI：
10.1093/cid/cit136
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发表时间：
2013-06-15
影响因子：
11.8
通讯作者：
Pfaller, Michael A.
中科院分区：
文献类型：
--
作者：
Alexander, Barbara D.;Johnson, Melissa D.;Pfaller, Michael A.
背景资料。对氟康唑(FLC)的耐药性在光滑棘球绦虫中很常见，棘球绦虫类药物经常被用作一线治疗。对棘球绦虫治疗的耐药性与FKS1和FKS2基因改变有关。我们回顾了杜克医院在过去十年(2001-2010年)所有的光滑葡萄球菌血流感染患者的记录，并将治疗结果与最低抑菌浓度(MIC)结果和FKS基因突变的存在进行了关联。测定了各分离株对FLC和棘球菌素类(阿尼度芬净、卡泊芬净和米卡芬净)的最低抑菌浓度(MIC)和FKS1、FKS2基因序列。对293例(313株)光滑念珠菌血液感染病例进行了分析。2001-2010年间，棘球菌素耐药性从4.9%上升到12.3%，对FLC的耐药性从18%上升到30%。78株FLC耐药株中，14.1%对1种或1种以上棘球菌素耐药。25株(7.9%)存在FKS突变。FKS突变株的预测因素是在棘球绦虫治疗之前(逐步多变量分析，优势比，19.647[95%可信区间，7.1958.1])。80%(8/10)的患者感染了对棘球绦虫具有中等或耐药MIC的FKS突变株，并接受了棘球绦虫治疗，最初没有反应或没有反应，但经历了复发。棘球绦虫耐药性正在增加，包括耐FLC的菌株。新的临床和实验室标准研究所的临床断点区分了野生型和具有临床意义的FKS1/FKS2突变的光滑念珠菌菌株。这些观察结果强调了了解机构内念珠菌的当地流行病学和耐药模式以及对光滑念珠菌棘球菌素类药物的敏感性测试以指导治疗决策的重要性。
Background. Fluconazole (FLC) resistance is common in C. glabrata and echinocandins are often used as first-line therapy. Resistance to echinocandin therapy has been associated with FKS1 and FKS2 gene alterations.Methods. We reviewed records of all patients with C. glabrata bloodstream infection at Duke Hospital over the past decade (2001-2010) and correlated treatment outcome with minimum inhibitory concentration (MIC) results and the presence of FKS gene mutations. For each isolate, MICs to FLC and echinocandins (anidulafungin, caspofungin, and micafungin) and FKS1 and FKS2 gene sequences were determined.Results. Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectively. Among the 78 FLC resistant isolates, 14.1% were resistant to 1 or more echinocandin. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, odds ratio, 19.647 [95% confidence interval, 7.19-58.1]). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but experienced a recurrence.Conclusions. Echinocandin resistance is increasing, including among FLC-resistant isolates. The new Clinical and Laboratory Standards Institute clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.