Understanding Echinocandin Resistance in the Emerging Pathogen Candida Auris

has simultaneously emerged on five continents as a fungal pathogen causing nosocomial outbreaks. The challenges in the treatment of infections are the variable antifungal susceptibility profiles among clinical isolates and the development of resistance to single or multiple classes of available antifungal drugs. Here, the susceptibility to echinocandin antifungal drugs was determined and sequencing was performed on 106 clinical isolates. Four isolates were identified to be resistant to all tested echinocandins (MIC ≥ 4 mg/liter) and harbored an S639F mutation in hot spot region 1. All remaining isolates were wild type (WT) and echinocandin susceptible, with micafungin being the most potent echinocandin (MIC = 0.125 mg/liter). Antifungal susceptibility testing with caspofungin was challenging due to the fact that all WT isolates exhibited an Eagle effect (also known as the paradoxical growth effect), which occurred at various intensities. To assess whether the Eagle effect resulted in pharmacodynamic resistance, 8 representative isolates were evaluated for their drug response in a murine model of invasive candidiasis. All isolates were susceptible to caspofungin at a human therapeutic dose, except for those harboring the S639F mutation. The data suggest that only isolates carrying mutations in are echinocandin resistant and that routine testing of isolates for susceptibility to caspofungin by the broth microdilution method should be viewed cautiously or avoided.