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Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates.
Frontiers in Cellular and Infection Microbiology ( IF 4.6 ) Pub Date : 2020-05-21 , DOI: 10.3389/fcimb.2020.00206
Amir Arastehfar 1 , Farnaz Daneshnia 1 , Mohammad Javad Najafzadeh 2 , Ferry Hagen 1, 3, 4 , Shahram Mahmoudi 5 , Mohammadreza Salehi 6 , Hossein Zarrinfar 7 , Zahra Namvar 8 , Zahra Zareshahrabadi 9 , Sadegh Khodavaisy 10 , Kamiar Zomorodian 9 , Weihua Pan 11 , Bart Theelen 1 , Markus Kostrzewa 12 , Teun Boekhout 1, 13 , Cornelia Lass-Flörl 14
Affiliation  

Clonal expansion of fluconazole resistant (FLZ-R) Candida parapsilosis 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 C. parapsilosis blood isolates. Candida parapsilosis species complex blood isolates (n = 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 ERG11, MRR1 and hotspots 1/2 (HS1/2) of FKS1 were sequenced to assess the azole and echinocandin resistance mechanisms, respectively. Ninety-four C. parapsilosis and four Candida orthopsilosis 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 (P = 0.02, α <0.05) and Mashhad was significantly associated with mortality (P = 0.03, α <0.05). Overall, we found a low level of antifungal resistance for Iranian C. parapsilosis 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.

中文翻译:

伊朗近平滑念珠菌种复杂血液分离株抗真菌抗性的分子流行病学、临床特征、抗真菌敏感性特征和分子机制的评估。

在许多国家,越来越多地发现对氟康唑耐药 (FLZ-R) 近平滑念珠菌分离株的克隆扩增,而没有研究探讨伊朗近平滑念珠菌血液分离株的抗真菌药敏模式、遗传多样性和临床信息。从位于三个主要城市的九家医院中回收了近平滑念珠菌种复杂血液分离株(n = 98),通过 MALDI-TOF MS 进行鉴定,并通过 AFLP 指纹图谱检查它们的遗传相关性。CLSI-M27-A3 和 ERG11、MRR1 和 FKS1 的热点 1/2 (HS1/2) 进行了抗真菌敏感性测试,分别用于评估唑类和棘白菌素耐药机制。从 90 名患者中鉴定出 94 株近平滑念珠菌和 4 株假丝酵母菌。只有 43 名患者接受了以氟康唑为主要抗真菌药物的全身抗真菌药物治疗。总体死亡率为 46.6% (42/90),与未接受治疗的患者 (17/47) 相比,接受全身抗真菌药物治疗的患者 (25/43) 的死亡率最高。尽管抗真菌耐药性很少见,但一种分离株具有多重耐药性(FLZ = 16 μg/ml 和米卡芬净 = 8 μg/ml),并且感染患者对 FLZ 预防显示治疗失败。在所研究的基因中未发现引起唑和棘白菌素抗性的突变。AFLP 揭示了五种基因型 (G),G1 是主要的一种 (59/94;62.7%)。临床结果与城市显着相关(P = 0.02,α <0.05),马什哈德与死亡率显着相关(P = 0.03,α <0.05)。总体而言,我们发现伊朗 C. 近平滑肌血液分离株,但上述 MDR 菌株有可能成为未来感染的源头,并对未接受抗真菌治疗的患者的抗真菌治疗提出挑战。AFLP 分型结果保证使用其他解析分型方法进行确认。
更新日期:2020-05-21
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