The Prospective Value of Genetic Testing for Antifungal Susceptibility for Candida Auris

The Prospective Value of Genetic Testing for Antifungal Susceptibility for Candida Auris


Image credit: pexels, Pavel Danilyuk

Candida auris (C auris) is a concerning fungal infection that continues to see an increase in incidence rates. Since it was first discovered in the United States in 2016, it has grown exponentially. In 2023, there were 4,514 new cases of C auris in the country.1

In addition to rising incidence rates, the fungal infection has been shown to be highly resistant to all 3 classes of antifungals. “Overall, about 90% of C auris strains have acquired resistance to at least 1 drug, 30% to 41% are resistant to 2 drugs and about 4% are resistant to all 3 antifungals,” investigators wrote in a previous study.2

And lastly, the fungal infection has a high mortality rate of between 30%-50%. Compounding the aforementioned issues is the patient profile of who contracts C auris. It is mostly limited to people who are older, have weakened immune systems, are experiencing multiple medical problems, and are either hospitalized or in long-term care nursing facilities (LTCF) where these infections can colonize easily.

In a previous interview with Contagion, Meghan Lyman, MD, medical officer, Mycotic Diseases Branch, Centers for Disease Control and Prevention (CDC) spoke of the need for improved detection and infection control of C auris. “Without increased efforts to do this, C auris is going to continue to spread across the US and become endemic like other superbugs,” she said.

With resistance in a highly vulnerable population, time-to-treat becomes a major issue. As such, a novel testing approach being studied may help in understanding resistance and susceptibility.

Marie Smithgall, MD, assistant professor of Pathology and Cell Biology at the Columbia University Irving Medical Center, led a team of investigators who tested antifungal resistance genes in samples of C auris isolated from 66 patients. The samples underwent both whole-genome sequencing (WGS) and Sanger sequencing genetic testing, in order to identify each sample’s genetic fingerprint. The samples also underwent traditional susceptibility testing and were grown in the presence of seven major antifungal drugs.3

The results were published in the journal Clinical Chemistry.

By comparing the genomic and susceptibility test results, the researchers confirmed that a number of different mutations in C auris’s FKS1 gene cause resistance to echinocandins, which are the class of antifungal drugs that currently serve as the first line treatment.3

The investigators showed that:

  • The Ser639Tyr FKS1 mutation and Arg135Ser mutation are associated with resistance to the antifungal drugs micafungin and anidulafungin.
  • The Met690Ile mutation is associated with resistance to caspofungin.3

These findings prove that genomic sequencing can serve as an alternative to susceptibility testing. “With potential resistance to all 3 major antifungal classes of drugs, C auris is an emerging public health threat. Early detection of echinocandin resistance by molecular methods could impact treatment course to include novel antifungal agents,” Smithgall said in a statement. “Overall WGS serves as a powerful tool for molecular surveillance to help monitor, detect, and curb the spread of C auris.”3

References
1. Tracking C auris. CDC. December 9, 2024. Accessed January 6, 2025. https://www.cdc.gov/candida-auris/tracking-c-auris/index.html
2. Sharma C, Kadosh D. Perspective on the origin, resistance, and spread of the emerging human fungal pathogen Candida auris. PLoS Pathog. 2023;19(3):e1011190. Published 2023 Mar 23. doi:10.1371/journal.ppat.1011190
3.Genetic testing could improve treatment for patients with the virulent multidrug-resistant fungus Candida auris. January 3, 2025. Accessed January 6, 2025.
https://www.prnewswire.com/news-releases/genetic-testing-could-improve-treatment-for-patients-with-the-virulent-multidrug-resistant-fungus-candida-auris-302342153.html



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