How does antifungal resistance vary in Candida (Candidozyma) auris and its clades? Quantitative and qualitative analyses and their clinical implications

Abstract

Background: Candida (Candidozyma) auris is a multidrug-resistant yeast that emerged as a significant health care-associated pathogen. It is classified as an urgent threat to public health due to the high resistance to available antifungal agents. Globally six distinct clades of C. auris have been identified with varying antifungal susceptibility patterns and geographical distributions.

Objectives: The aim of this review is to investigate the (published) antifungal susceptibility profiles of different C. auris clades to identify those with a higher prevalence of resistance.

Sources: A comprehensive literature review was conducted using PubMed, SciELO, Google Scholar, and MEDLINE databases to collect data on MIC distributions and clade designations of C. auris strains.

Content: A total of 1031 C. auris strains were included. Clades I and III, which are closely related phylogenetically, displayed the highest resistance rates, particularly to fluconazole, with 94% and 96% of isolates, respectively. Clade IV also exhibited resistance to both azoles and echinocandins. In contrast, clades II, V, and VI had lower resistance rates, with clade VI being entirely susceptible to fluconazole. Anidulafungin demonstrated the greatest efficacy across all clades, with resistance rates ranging from 0% to 3.67%. Furthermore, clades V and VI showed complete susceptibility to all antifungal agents evaluated.

Implications: This study highlights significant variations in antifungal resistance profiles across the six C. auris clades. Clades I, III, and IV stand out because of their multidrug resistance, particularly to fluconazole and amphotericin B, posing serious challenges for treatment. Continuous global surveillance and tailored management strategies are essential for controlling C. auris infections, especially in highly resistant clades. Enhanced diagnostic capabilities and further genomic studies are critical to understanding the evolving nature of resistance in this emerging pathogen and improving therapeutic outcomes. Clade-specific antifungal resistance in C. auris requires monitoring to optimize therapy selection during outbreaks.

Keywords: Azoles; Epidemiology; Global emergence; Outbreaks.