A notable azole-nonsusceptible Candida orthopsilosis in the Candida parapsilosis complex isolated from onychomycosis in Hue City, Central Vietnam

Abstract The Candida parapsilosis complex, consisting of C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis, is a major cause of Candida onychomycosis. Increasing reports of high levels of resistance to antifungal drugs, particularly fluconazole and echinocandin, have raised concerns about C. parapsilosis complex. This study investigates antifungal resistance and hydrolytic enzyme activity in these species. Species were identified using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and internal transcribed spacer (ITS) 1-4 sequencing. Antifungal susceptibility was assessed using Sensititre™ YeastOne™. Hydrolytic enzyme production was assessed by agar plate culture. Among 43 isolates, C. parapsilosis sensu stricto was most prevalent (48.8%, n = 21/43), followed by C. orthopsilosis (39.6%, n = 17/43) and C. metapsilosis (11.6%, n = 5/43). All C. parapsilosis sensu stricto isolates were susceptible to antifungal agents, except 4.8% (n = 1/21) showing dose-dependent susceptibility to fluconazole and 4.8% (n = 1/21) resistance to amphotericin B. Candida orthopsilosis showed significant resistance to fluconazole and voriconazole (52.9% each, n = 9/17), posaconazole (23.5%, n = 4/17), and low resistance to amphotericin B (5.9%, n = 1/17). One C. metapsilosis isolate (20%) showed cross-resistance to fluconazole and voriconazole, and another (20%) was resistant to 5-flucytosine. Enzymatic assays showed higher protease and lipase activity in C. parapsilosis sensu stricto and C. orthopsilosis compared to C. metapsilosis, with C. parapsilosis sensu stricto showing the highest protease activity. Comprehensive research into antifungal susceptibility and virulence factors of the C. parapsilosis species complex is essential to monitor the growing threat of antifungal resistance and to better understand its role in onychomycosis pathogenesis.