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Front Cell Infect Microbiol. 2019 Jul 30;9:264. doi: 10.3389/fcimb.2019.00264. eCollection 2019.

Molecular Identification, Genotypic Diversity, Antifungal Susceptibility, and Clinical Outcomes of Infections Caused by Clinically Underrated Yeasts, Candida orthopsilosis, and Candida metapsilosis: An Iranian Multicenter Study (2014-2019).

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Department of Medical Mycology, Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands.
Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Mycology and Parasitology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Faculty of Engineering, Sabzevar University of New Technology, Sabzevar, Iran.
Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands.
Laboratory of Medical Mycology, Jining No. 1 People's Hospital, Jining, China.
Institute of Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, Netherlands.


Despite the increasing occurrence of Candida orthopsilosis and Candida metapsilosis in clinical settings, little is known about their microbiological and clinical properties. Herein, we conducted a national retrospective study (2014-2019) from multiple centers in Iran. Among the 1,770 Candida isolates collected, we identified 600 Candida parapsilosis species complex isolates. Isolate identification was performed by 9-plex PCR, matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF MS), and rDNA sequencing, and antifungal susceptibility testing (AFST) followed CLSI M27-A3/S4; genotyping was performed by amplified fragment length polymorphism (AFLP) analysis; and clinical information was mined. Thirty-one isolates of C. orthopsilosis from various clinical sources, one mixed sample (blood) concurrently containing C. orthopsilosis and C. parapsilosis and one isolate of C. metapsilosis from a nail sample were identified. Although both 9-plex PCR and MALDI-TOF successfully identified all isolates, only 9-plex PCR could identify the agents in a mixed sample. For the C. orthopsilosis isolates, resistance (non-wild type) was noted only for itraconazole (n = 4; 12.5%). Anidulafungin and fluconazole showed the highest and voriconazole had the lowest geometric mean values. AFLP analysis showed three main and four minor genotypes. Interestingly, 90% of nail isolates clustered with 80% of the blood isolates within two clusters, and four blood isolates recovered from four patients admitted to a hospital clustered into two genotypes and showed a high degree of similarity (>99.2%), which suggests that C. orthopsilosis disseminates horizontally. Supported by our data and published case studies, C. orthopsilosis and C. metapsilosis can be linked to challenging clinical failures, and successful outcomes are not always mirrored by in vitro susceptibility. Accordingly, conducting nationwide studies may provide more comprehensive data, which is required for a better prognosis and clinical management of patients.


AFLP genotyping; AFST; C. metapsilosis; C. orthopsilosis; C. parapsilosis species complex; Iran; clonality

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