Low Level of Antifungal Resistance in Iranian Isolates of Candida glabrata Recovered from Blood Samples in a Multicenter Study from 2015 to 2018 and Potential Prognostic Values of Genotyping and Sequencing of PDR1
Low Level of Antifungal Resistance in Iranian Isolates of Candida glabrata Recovered from Blood Samples in a Multicenter Study from 2015 to 2018 and Potential Prognostic Values of Genotyping and Sequencing of PDR1
复制标题
2015 年至 2018 年多中心研究中从血液样本中回收的伊朗光滑念珠菌分离株的低水平抗真菌耐药性以及 PDR1 基因分型和测序的潜在预后价值
DOI：
10.1128/aac.02503-18
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发表时间：
2019-07-01
影响因子：
4.9
通讯作者：
Boekhout, Teun
中科院分区：
文献类型：
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作者：
Arastehfar, Amir;Daneshnia, Farnaz;Boekhout, Teun
建立有效的经验性抗真菌治疗需要进行国家监测研究。在此，我们报告的临床结果感染和伊朗分离的光滑念珠菌的微生物学特征来自患者的念珠菌血症。建立有效的经验性抗真菌治疗需要进行国家监测研究。在此，我们报告的临床结果感染和伊朗分离的光滑念珠菌的微生物学特征来自患者的念珠菌血症。C. glabrata分离株回顾性地收集了四个主要城市在伊朗，确定了21重PCR，基质辅助激光解吸电离飞行时间质谱，大亚基的核糖体DNA测序和基因型扩增片段长度多态性（AFLP）。研究了FKS 1和FKS 2的PDR 1、ERG 11和热点1（HS 1）突变，并进行了抗真菌药敏试验（AFST）（采用CLSI M27-A3和M27-S4方法）。70株C.从65名患者中收集了光滑的，中位年龄为58岁。氟康唑应用最广泛（29.23%），疗效最差。总体粗死亡率为35.4%。仅1株对氟康唑耐药，卡泊芬净和伏立康唑敏感的非野生型（非WT）菌株分别占57.7%和37.5%。所有分离株均表现出白曲霉素B、泊沙康唑和伊曲康唑的WT表型。FKS 1和FKS 2的HS 1没有任何突变，而PDR 1和ERG 11中观察到大量错义突变。AFLP将分离株分为9种基因型，其中基因型1和2与死亡率显著相关（P = 0.034和P = 0.022，α < 0.05）。此外，83.3%感染携带PDR 1中单一新突变T745 A的菌株的患者，尽管接受了氟康唑或卡泊芬净治疗，仍死亡。总体而言，伊朗分离的C.对主要抗真菌药物敏感。应用基因分型技术和特定基因（PDR 1）的测序可能具有预后意义。
Establishing an effective empirical antifungal therapy requires that national surveillance studies be conducted. Herein, we report the clinical outcome of infections with and the microbiological features of Iranian isolates of Candida glabrata derived from patients suffering from candidemia. ABSTRACT Establishing an effective empirical antifungal therapy requires that national surveillance studies be conducted. Herein, we report the clinical outcome of infections with and the microbiological features of Iranian isolates of Candida glabrata derived from patients suffering from candidemia. C. glabrata isolates were retrospectively collected from four major cities in Iran; identified by a 21-plex PCR, matrix-assisted laser desorption ionization–time of flight mass spectrometry, and large subunit of ribosomal DNA sequencing; and genotyped by amplified fragment length polymorphism (AFLP). Mutations in PDR1, ERG11, and hot spot 1 (HS1) of FKS1 and FKS2 were investigated, and antifungal susceptibility testing (AFST) was performed (by the CLSI M27-A3 and M27-S4 methods). Seventy isolates of C. glabrata were collected from 65 patients with a median age of 58 years. Fluconazole was the most widely used (29.23%) and least effective antifungal agent. The overall crude mortality rate was 35.4%. Only one strain was resistant to fluconazole, and 57.7% and 37.5% of the isolates were non-wild type (non-WT) for susceptibility to caspofungin and voriconazole, respectively. All isolates showed the WT phenotype for amphotericin B, posaconazole, and itraconazole. HS1 of FKS1 and FKS2 did not harbor any mutations, while numerous missense mutations were observed in PDR1 and ERG11. AFLP clustered our isolates into nine genotypes; among them, genotypes 1 and 2 were significantly associated with a higher mortality rate (P = 0.034 and P = 0.022, α < 0.05). Moreover, 83.3% of patients infected with strains harboring a single new mutation in PDR1, T745A, died despite treatment with fluconazole or caspofungin. Overall, Iranian isolates of C. glabrata were susceptible to the major antifungal drugs. Application of genotyping techniques and sequencing of a specific gene (PDR1) might have prognostic implications.