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伊朗 2015 年至 2018 年多中心研究中从血样中分离的光滑念珠菌的抗真菌药物低水平耐药性及基因分型和测序的潜在预后价值

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 .

机构信息

Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands.

Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Antimicrob Agents Chemother. 2019 Jun 24;63(7). doi: 10.1128/AAC.02503-18. Print 2019 Jul.

DOI:10.1128/AAC.02503-18
PMID:30936110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6591624/
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 derived from patients suffering from candidemia. 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 , , and hot spot 1 (HS1) of and were investigated, and antifungal susceptibility testing (AFST) was performed (by the CLSI M27-A3 and M27-S4 methods). Seventy isolates of 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 and did not harbor any mutations, while numerous missense mutations were observed in and AFLP clustered our isolates into nine genotypes; among them, genotypes 1 and 2 were significantly associated with a higher mortality rate ( = 0.034 and  = 0.022, α < 0.05). Moreover, 83.3% of patients infected with strains harboring a single new mutation in , T745A, died despite treatment with fluconazole or caspofungin. Overall, Iranian isolates of were susceptible to the major antifungal drugs. Application of genotyping techniques and sequencing of a specific gene () might have prognostic implications.

摘要

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,我们报告了从患有念珠菌血症的患者中分离出的伊朗 株的临床结果和微生物特征。从伊朗四个主要城市回顾性收集 株;通过 21 重 PCR、基质辅助激光解吸电离飞行时间质谱和核糖体 DNA 大亚基测序进行鉴定;并通过扩增片段长度多态性 (AFLP) 进行基因分型。研究了 、 、 和热点 1 (HS1) 的突变,并进行了抗真菌药敏试验 (AFST) (CLSI M27-A3 和 M27-S4 方法)。从 65 名 58 岁中位年龄的患者中收集了 70 株 。氟康唑是最广泛使用(29.23%)但效果最差的抗真菌药物。总体粗死亡率为 35.4%。只有一株对氟康唑耐药,57.7%和 37.5%的分离株对卡泊芬净和伏立康唑的敏感性是非野生型 (非 WT)。所有分离株对两性霉素 B、泊沙康唑和伊曲康唑均表现出 WT 表型。 、 的 HS1 没有携带任何突变,而 、 的 AFLP 观察到许多错义突变。我们的分离株聚类为 9 种基因型;其中,基因型 1 和 2 与更高的死亡率显著相关(=0.034 和=0.022,α<0.05)。此外,尽管用氟康唑或卡泊芬净治疗,感染携带 、 T745A 单一新突变的菌株的 83.3%的患者死亡。总体而言,伊朗 株对主要抗真菌药物敏感。基因分型技术的应用和特定基因()的测序可能具有预后意义。

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