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伊朗念珠菌复合体血分离株的分子流行病学、临床特征、抗真菌药敏谱评价及耐药分子机制研究。

Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Species Complex Blood Isolates.

机构信息

Yeast Biodiversity Department, Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands.

Department of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Front Cell Infect Microbiol. 2020 May 21;10:206. doi: 10.3389/fcimb.2020.00206. eCollection 2020.

Abstract

Clonal expansion of fluconazole resistant (FLZ-R) isolates is increasingly being identified in many countries, while there is no study exploring the antifungal susceptibility pattern, genetic diversity, and clinical information for Iranian blood isolates. species complex blood isolates ( = 98) were recovered from nine hospitals located in three major cities, identified by MALDI-TOF MS, and their genetic relatedness was examined by AFLP fingerprinting. Antifungal susceptibility testing followed CLSI-M27-A3 and and hotspots 1/2 (HS1/2) of were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four and four isolates were identified from 90 patients. Only 43 patients received systemic antifungal drugs with fluconazole as the main antifungal used. The overall mortality rate was 46.6% (42/90) and death mostly occurred for those receiving systemic antifungals (25/43) relative to those not treated (17/47). Although, antifungal-resistance was rare, one isolate was multidrug-resistant (FLZ = 16 μg/ml and micafungin = 8 μg/ml) and the infected patient showed therapeutic failure to FLZ prophylaxis. Mutations causing azole and echinocandin resistance were not found in the genes studied. AFLP revealed five genotypes (G) and G1 was the main one (59/94; 62.7%). Clinical outcome was significantly associated with city ( = 0.02, α <0.05) and Mashhad was significantly associated with mortality ( = 0.03, α <0.05). Overall, we found a low level of antifungal resistance for Iranian blood isolates, but the noted MDR strain can potentially become the source of future infections and challenge the antifungal therapy in antifungal-naïve patients. AFLP typing results warrants confirmation using other resolutive typing methods.

摘要

氟康唑耐药(FLZ-R)分离株的克隆扩张在许多国家越来越多地被发现,而目前尚无研究探讨伊朗血液分离株的抗真菌药敏模式、遗传多样性和临床信息。从三个主要城市的九家医院共分离到 98 株种复合体血液分离株(=98),通过基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)进行鉴定,并通过 AFLP 指纹图谱检测其遗传相关性。按照 CLSI-M27-A3 标准进行抗真菌药敏试验,分别对 1/2(HS1/2)热点区和进行测序,以评估唑类和棘白菌素类的耐药机制。从 90 名患者中鉴定出 94 株和 4 株,只有 43 名患者接受了全身性抗真菌药物治疗,其中氟康唑是主要的抗真菌药物。总的死亡率为 46.6%(42/90),且死亡主要发生在接受全身性抗真菌治疗的患者(25/43),而未接受治疗的患者(17/47)死亡率较低。虽然抗真菌耐药性罕见,但有 1 株分离株为多药耐药(FLZ=16μg/ml,米卡芬净=8μg/ml),感染患者对 FLZ 预防治疗失败。在所研究的基因中未发现导致唑类和棘白菌素类耐药的突变。AFLP 显示有 5 种基因型(G),G1 是主要的基因型(59/94;62.7%)。临床结局与城市显著相关(=0.02,α<0.05),马什哈德与死亡率显著相关(=0.03,α<0.05)。总的来说,我们发现伊朗血液分离株的抗真菌耐药率较低,但 noted MDR 株可能成为未来感染的来源,并对抗真菌治疗无经验的患者的抗真菌治疗构成挑战。AFLP 分型结果需要使用其他分辨率分型方法进行确认。

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