Multicentre Study of Candida parapsilosis Blood Isolates in Türkiye Highlights an Increasing Rate of Fluconazole Resistance and Emergence of Echinocandin and Multidrug Resistance.

Objectives: Worldwide emergence of clonal outbreaks caused by fluconazole-resistant (FLCR) and the recent emergence of echinocandin- and multidrug-resistant (ECR and MDR) Candida parapsilosis isolates pose serious threats to modern clinics. Conducting large-scale epidemiological studies aimed at determining the genetic composition and antifungal resistance rates is necessary to devise antifungal stewardship and infection control strategies at international, national and local levels. Despite being severely hit by outbreaks due to FLCR C. parapsilosis isolates, such knowledge at the national level is lacking in Türkiye. Herein, we conducted a prospective multicentre study involving five major clinical centres in Türkiye to determine antifungal resistance rates, underlying mechanisms and genetic composition of all isolates.

Methods: In total, 341 isolates were collected from 265 patients including clinical information. Antifungal susceptibility testing against common antifungals was performed in addition to sequencing of ERG11 and FKS1. Last, isolates were genotyped with short tandem repeat (STR) genotyping to investigate potential nosocomial transmission.

Results: The FLCR rate was 26.7% (91/341), out of which 75.8% (69/91) harboured the ERG11^Y132F mutation. Patients infected with FLCR isolates had a higher mortality rate compared to their susceptible counterparts (49% for FLCR vs. 42% for susceptible). ECR rate was 2.1% (7/341) and isolates carried FKS1^{F652L/R658G/W1370R} mutations. Concerningly, four ECR isolates were MDR. FLCR isolates grouped in distinct clusters without evidence of inter-hospital transmission, whereas large clusters containing susceptible isolates from all centres were noted.

Conclusion: Overall, the increasing prevalence of FLCR C. parapsilosis at national level and the emergence of ECR and MDR isolates pose serious clinical challenges in Türkiye. Therefore, conducting large-scale epidemiological studies are critical to determine the trend of antifungal resistance and to tailor pertinent antifungal stewardship and infection control strategies to effectively curb the spread of drug-resistant C. parapsilosis.