Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure
Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure
复制标题
土耳其光滑念珠菌血液分离株的抗真菌耐药性水平较低：氟康唑最低抑菌浓度和 FKS 突变可以预测治疗失败
DOI：
10.1111/myc.13104
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发表时间：
2020-08-05
期刊：
影响因子：
4.9
通讯作者：
Lass-Floerl, Cornelia
中科院分区：
文献类型：
--
作者：
Arastehfar, Amir;Daneshnia, Farnaz;Lass-Floerl, Cornelia
研究背景光滑假丝酵母菌是土耳其念珠菌血症的第三大致病因素；然而，有关抗真菌耐药机制和与其临床意义相关的基因多样性的数据有限。目的在一项多中心的回顾性研究中，评估耐药菌株的基因多样性、抗真菌敏感性、耐药机制及其与患者预后的关系。患者/方法对107例患者的分离株进行ITS测序，并通过多位点微卫星分型、抗真菌药敏试验、PDR1和FKS1/2热点(HSS)测序进行分析。结果2014-2019年鄂西大学医院光滑念珠菌感染率是2005-2014年的两倍。6株分析菌株的氟康唑最低抑菌浓度为32微克/毫升，其中5株具有独特的PDR1突变。虽然未检测到棘球绦虫耐药，但有3株分离株存在HS1-Fks1(S629T，n=1)和HS1-Fks2(S663P，n=2)突变，其中1株也对氟康唑耐药。所有携带HS-FKS突变和/或氟康唑MIC>；=32mU/m L的患者(除1例无临床资料外)均对棘球绦虫和氟康唑治疗失败；在EGE(n=4)和Gulhane(n=3)医院收集了7株此类分离株，最近检测到6株。在34个已鉴定的基因型别中，没有一个与死亡率相关，也没有一个对氟康唑耐药菌株具有浓缩性。结论抗真菌药敏试验与HS-FKS测序相结合可预测棘球菌素类药物的Tf，而氟康唑MIC>；=32mU g/m L可预测Tf。最近出现的与抗真菌转铁蛋白相关的光滑葡萄球菌分离株在土耳其值得进行未来的综合性前瞻性研究。
Background Candida glabratais the third leading cause of candidaemia in Turkey; however, the data regarding antifungal resistance mechanisms and genotypic diversity in association with their clinical implication are limited. Objectives To assess genotypic diversity, antifungal susceptibility and mechanisms of drug resistance ofCglabratablood isolates and their association with patients' outcome in a retrospective multicentre study. Patients/Methods Isolates from 107 patients were identified by ITS sequencing and analysed by multilocus microsatellite typing, antifungal susceptibility testing, and sequencing ofPDR1andFKS1/2hotspots (HSs). Results Candida glabrataprevalence in Ege University Hospital was twofold higher in 2014-2019 than in 2005-2014. Six of the analysed isolates had fluconazole MICs >= 32 mu g/mL; of them, five harboured uniquePDR1mutations. Although echinocandin resistance was not detected, three isolates had mutations in HS1-Fks1 (S629T, n = 1) and HS1-Fks2 (S663P, n = 2); one of the latter was also fluconazole-resistant. All patients infected with isolates carrying HS-FKSmutations and/or demonstrating fluconazole MIC >= 32 mu g/mL (except one without clinical data) showed therapeutic failure (TF) with echinocandin and fluconazole; seven such isolates were collected in Ege (n = 4) and Gulhane (n = 3) hospitals and six detected recently. Among 34 identified genotypes, none were associated with mortality or enriched for fluconazole-resistant isolates. Conclusion Antifungal susceptibility testing should be supplemented with HS-FKSsequencing to predict TF for echinocandins, whereas fluconazole MIC >= 32 mu g/mL may predict TF. Recent emergence ofC glabrataisolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey.