Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates
Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates
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伊朗近平滑念珠菌种复合血液分离株的分子流行病学、临床特征、抗真菌药敏概况和抗真菌耐药性分子机制的评估
DOI：
10.3389/fcimb.2020.00206
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发表时间：
2020-05-21
影响因子：
5.7
通讯作者：
Lass-Floerl, Cornelia
中科院分区：
文献类型：
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作者：
Arastehfar, Amir;Daneshnia, Farnaz;Lass-Floerl, Cornelia
在许多国家，越来越多地发现了耐氟康唑（FLZ-R）假丝酵母（Candida parapsilosis）分离株的克隆扩增，而伊朗假丝酵母（Candida parapsilosis）血液分离株的抗真菌药敏模式、遗传多样性和临床信息尚无研究。从3个主要城市的9家医院分离到假丝酵母菌复合血分离株98株，采用MALDI-TOF质谱鉴定，并采用AFLP指纹图谱检测其遗传亲缘关系。采用CLSI-M27-A3和FKS1的ERG11、MRR1和热点1/2 （HS1/2）进行抗真菌药敏试验，分别评估其对唑和棘白菌素的耐药机制。从90例患者中分离出94株假丝酵母菌和4株矫形念珠菌。仅43例患者接受了以氟康唑为主的全身抗真菌药物治疗。总死亡率为46.6%(42/90)，死亡主要发生在接受全身抗真菌药物治疗的患者（25/43）相对于未接受治疗的患者（17/47）。1株耐多药菌株（FLZ = 16 μg/ml, micafungin = 8 μg/ml），感染患者对FLZ预防治疗失败。在所研究的基因中未发现引起唑和棘白菌素耐药的突变。AFLP显示5种基因型(G)， G1为主要基因型（59/94;62.7%）。临床转归与城市相关（P = 0.02, α <0.05）， Mashhad与病死率相关（P = 0.03, α <0.05）。总体而言，我们发现伊朗假丝酵母菌血液分离株具有低水平的抗真菌耐药性，但值得注意的耐多药菌株可能成为未来感染的来源，并对antifungal-naïve患者的抗真菌治疗构成挑战。AFLP分型结果需要使用其他判别分型方法进行确认。
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.