Candida parapsilosis and echinocandins: should the clinical laboratory drop anidulafungin Etest from the susceptibility testing panel?

Antifungal susceptibility testing (AFST) is essential for clinical decisions to effectively select optimal therapy against fungal infections. Reference standard broth microdilution methods provide accurate results; however, they are more challenging and time-consuming compared to conventional susceptibility testing methods such as gradient diffusion strips (Etest). This study assessed the Clinical and Laboratory Standards Institute (CLSI) yeast protocol and Etest for determining the echinocandin susceptibility profile (anidulafungin, caspofungin, micafungin, and rezafungin) in Candida parapsilosis isolates (n = 60). A full agreement (100%) was observed between Etest and CLSI for caspofungin, micafungin, and rezafungin, but surprisingly, the agreement for anidulafungin was only 43.3%. Notably, 56.6% of isolates were anidulafungin resistant by Etest, whereas CLSI detected no resistance. Analysis of fks1 gene hotspots (HS1 and HS2) revealed no mutations, proving that anidulafungin susceptibility results are method-dependent rather than a consequence of actual resistance. Our findings suggest that Etest may overestimate anidulafungin resistance in C. parapsilosis, which can lead to false resistance categorization. The low agreement between the two methods, Etest and CLSI, highlights the need to address these issues through improved quality control of the anidulafungin Etest or methodological adjustments. Given that anidulafungin is considered the leading drug in AFST for C. parapsilosis, caution is recommended when interpreting Etest results without confirmation via broth microdilution. Since these discrepancies in categorization occur for a specific species and a particular antifungal, anidulafungin, within the echinocandin class, rather than for all agents in that class (with anidulafungin also serving as the reference agent in AFST), this may suggest that, in the case of C. parapsilosis, either an alternative method should be used for anidulafungin susceptibility testing, or other echinocandins should be considered as reference agents in clinical settings.