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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.

frontiers in cellular and infection microbiology

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)