ORIGINAL RESEARCH published: 21 May 2020 doi: 10.3389/fcimb.2020.00206 Frontiers in Cellular and Infection Microbiology | www.frontiersin.org 1 May 2020 | Volume 10 | Article 206 Edited by: Anuradha Chowdhary, University of Delhi, India Reviewed by: Maurizio Sanguinetti, Catholic University of the Sacred Heart, Italy Pilar Escribano, Instituto de Investigación Sanitaria Gregorio Marañón, Spain *Correspondence: Sadegh Khodavaisy sadegh_7392008@yahoo.com Kamiar Zomorodian zomorodian2@yahoo.com Weihua Pan panweihua@smmu.edu.cn † These authors have contributed equally to this work Specialty section: This article was submitted to Fungal Pathogenesis, a section of the journal Frontiers in Cellular and Infection Microbiology Received: 25 November 2019 Accepted: 16 April 2020 Published: 21 May 2020 Citation: Arastehfar A, Daneshnia F, Najafzadeh MJ, Hagen F, Mahmoudi S, Salehi M, Zarrinfar H, Namvar Z, Zareshahrabadi Z, Khodavaisy S, Zomorodian K, Pan W, Theelen B, Kostrzewa M, Boekhout T and Lass-Flörl C (2020) Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates. Front. Cell. Infect. Microbiol. 10:206. doi: 10.3389/fcimb.2020.00206 Evaluation of Molecular Epidemiology, Clinical Characteristics, Antifungal Susceptibility Profiles, and Molecular Mechanisms of Antifungal Resistance of Iranian Candida parapsilosis Species Complex Blood Isolates 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 and Cornelia Lass-Flörl 14 1 Yeast Biodiversity Department, Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands, 2 Department of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, 3 Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands, 4 Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, China, 5 Department of Medical Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran, 6 Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran, 7 Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran, 8 Department of Microbiology, School of Biological Sciences, Islamic Azad University, Tehran, Iran, 9 Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, 10 Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, 11 Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China, 12 Bruker Daltonik GmbH, Bremen, Germany, 13 Institute of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, Netherlands, 14 Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria 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