Genetic testing could improve treatment for patients with the virulent multidrug-resistant fungus Candida auris

Findings published in the special Clinical Chemistry issue, "Genomics: Current & emerging trends in the clinical laboratory"

WASHINGTON, Jan. 3, 2025 /PRNewswire/ -- A new study shows that genetic testing could be used to determine which drugs will — and won't — work for patients with Candida auris (C. auris), a multidrug-resistant yeast that causes life-threatening disease. These findings could improve treatment for C. auris infections by enabling patients to start taking effective antifungal agents sooner. The study was published today in a special issue of the Association for Diagnostics & Laboratory Medicine's (formerly AACC's) Clinical Chemistry journal titled "Genomics: Current & emerging trends in the clinical laboratory."

View the full study here: https://doi.org/10.1093/clinchem/hvae185

Since C. auris was identified in 2009, this pathogenic fungus has spread worldwide, causing severe illness in patients in healthcare facilities. Not only is it deadly, with an estimated mortality rate ranging from 30%-60%, but it is also particularly challenging to treat. One of the major reasons for this is that there are many different strains of C. auris, each of which has a different genetic profile that confers resistance to different antifungal drugs. Clinical labs currently use susceptibility testing to determine which drugs a specific strain of C. auris is resistant to. This involves growing a sample of a patient's C. auris in the presence of different antifungal agents and waiting to see which drug kills the fungus. However, it can be difficult to interpret C. auris susceptibility test results because minimum inhibitory concentration breakpoints — i.e., the lowest concentrations of different antifungal drugs that will stop its growth — have not been fully established.

Altogether, this means that healthcare professionals might waste precious time trying to figure out which antifungal drug will clear a patient's infection — and that time could mean the difference between life and death.

In order to improve testing for C. auris drug resistance, a team of researchers led by Dr. Marie C. Smithgall of the Columbia University Irving Medical Center in New York City examined antifungal resistance genes in samples of C. auris isolated from 66 patients at the researchers' institute. The samples underwent two types of genetic testing — whole-genome sequencing (WGS) and Sanger sequencing — which were used 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.

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 for invasive C. auris infections. Specifically, the researchers 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.

This demonstrates that genomic sequencing can identify which drugs a strain of C. auris is resistant to and can serve as an alternative to susceptibility testing.

"With potential resistance to all three 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. "Overall WGS serves as a powerful tool for molecular surveillance to help monitor, detect, and curb the spread of C. auris."

About the Association for Diagnostics & Laboratory Medicine (ADLM)

Dedicated to achieving better health through laboratory medicine, ADLM (formerly AACC) brings together more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, ADLM has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org.

Clinical Chemistry (clinchem.org) is the leading international journal of laboratory medicine, featuring nearly 400 peer-reviewed studies every year that help patients get accurate diagnoses and essential care. This vital research is advancing areas of healthcare ranging from genetic testing and drug monitoring to pediatrics and appropriate test utilization.

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SOURCE Association for Diagnostics & Laboratory Medicine (ADLM)