Shanghai Key Laboratory Molecular Medical Mycology, Shanghai, China.
Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands.
Mycoses. 2020 Sep;63(9):911-920. doi: 10.1111/myc.13104. Epub 2020 Aug 5.
Candida glabrata is 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.
To assess genotypic diversity, antifungal susceptibility and mechanisms of drug resistance of C glabrata blood 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 of PDR1 and FKS1/2 hotspots (HSs).
Candida glabrata prevalence in Ege University Hospital was twofold higher in 2014-2019 than in 2005-2014. Six of the analysed isolates had fluconazole MICs ≥ 32 µg/mL; of them, five harboured unique PDR1 mutations. 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-FKS mutations and/or demonstrating fluconazole MIC ≥ 32 µg/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.
Antifungal susceptibility testing should be supplemented with HS-FKS sequencing to predict TF for echinocandins, whereas fluconazole MIC ≥ 32 µg/mL may predict TF. Recent emergence of C glabrata isolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey.
光滑念珠菌是土耳其导致念珠菌血症的第三大原因；然而，关于抗真菌耐药机制和基因型多样性及其与临床意义的关联的数据有限。
在一项回顾性多中心研究中，评估 C 光滑念珠菌血培养分离株的基因型多样性、抗真菌药敏性和耐药机制及其与患者预后的关系。
患者/方法：通过 ITS 测序鉴定 107 例患者的分离株，并通过多位点微卫星分型、抗真菌药敏试验和 PDR1 和 FKS1/2 热点（HS）测序进行分析。
2014-2019 年，伊兹密尔大学医院 C 光滑念珠菌的流行率是 2005-2014 年的两倍。分析的 6 株分离株氟康唑 MIC 值≥32μg/mL；其中 5 株携带独特的 PDR1 突变。虽然未检测到棘白菌素耐药，但 3 株分离株在 HS1-Fks1（S629T，n=1）和 HS1-Fks2（S663P，n=2）中存在突变；其中一株还对氟康唑耐药。所有感染携带 HS-FKS 突变且/或氟康唑 MIC 值≥32μg/mL 的分离株（除 1 株无临床数据外）的患者均对棘白菌素和氟康唑治疗失败（TF）；这些分离株中有 7 株来自伊兹密尔（n=4）和古尔哈尼（n=3）医院，最近发现了 6 株。在鉴定的 34 种基因型中，没有一种与死亡率相关，也没有一种与氟康唑耐药分离株富集相关。
抗真菌药敏试验应辅以 HS-FKS 测序，以预测棘白菌素的 TF，而氟康唑 MIC 值≥32μg/mL 可能预测 TF。最近出现的与抗真菌 TF 相关的 C 光滑念珠菌分离株需要在土耳其进行未来全面的前瞻性研究。
