Tolerance and heteroresistance to echinocandins in Candida auris: conceptual issues, clinical implications, and outstanding questions

Candida auris is a significant public health threat due to its environmental persistence and multidrug resistance, with echinocandins being the preferred treatment. However, in addition to resistance, echinocandin tolerance and heteroresistance may contribute to treatment challenges. Echinocandin tolerance involves reduced drug-mediated killing, while heteroresistance is the ability of a small cell subset to grow at high drug concentrations. These phenomena may facilitate the emergence of full resistance and complicate clinical outcomes. The clinical significance of these mechanisms remains unclear, with limited data correlating them with treatment failures. Research is needed to understand their mechanisms and impact, develop streamlined and robust methods to detect them in clinical settings, and explore mitigation strategies. The pathogen’s range of drug adaptations demands innovative approaches like spatial transcriptomics to dissect these complex responses and improve patient outcomes.