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)

Despite the increasing occurrence of <i>Candida orthopsilosis</i> and <i>Candida metapsilosis</i> 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 <i>Candida</i> isolates collected, we identified 600 <i>Candida parapsilosis</i> 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 <i>C. orthopsilosis</i> from various clinical sources, one mixed sample (blood) concurrently containing <i>C. orthopsilosis</i> and <i>C. parapsilosis</i> and one isolate of <i>C. metapsilosis</i> 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 <i>C. orthopsilosis</i> isolates, resistance (non-wild type) was noted only for itraconazole (<i>n</i> = 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 <i>C. orthopsilosis</i> disseminates horizontally. Supported by our data and published case studies, <i>C. orthopsilosis</i> and <i>C. metapsilosis</i> can be linked to challenging clinical failures, and successful outcomes are not always mirrored by <i>in vitro</i> susceptibility. Accordingly, conducting nationwide studies may provide more comprehensive data, which is required for a better prognosis and clinical management of patients.