Overall, 25% and 13% of isolates were MDR and multi-azole resistant, respectively. The most common resistance combination was azoles and 5-flucytosine in 14% followed by azoles and amphotericin B in 7% and azoles and echinocandins in 2% of isolates.

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.

Candida auris is an emerging multidrug-resistant fungal pathogen causing nosocomial and invasive infections associated with high mortality. C. auris is commonly misidentified as several different yeast species by commercially available phenotypic identification platforms. Thus, there is an urgent need for a reliable diagnostic method. In this paper, we present fast, robust, easy-to-perform and interpret PCR and real-time PCR assays to identify C. auris and related species: Candida duobushaemulonii, Candida haemulonii, and Candida lusitaniae. Targeting rDNA region nucleotide sequences, primers specific for C. auris only or C. auris and related species were designed. A panel of 140 clinical fungal isolates was used in both PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The identification results from the assays were 100% concordant with DNA sequencing results. These molecular assays overcome the deficiencies of existing phenotypic tests to identify C. auris and related species.

Multiple Erg11 amino acid substitutions were identified in clinical isolates of Candida auris originating from India and Colombia. Elevated azole MICs were detected in Saccharomyces cerevisiae upon heterologous expression of C. auris ERG11 alleles that encoded for Y132F or K143R substitutions; however, expression of alleles encoding I466M, Y501H, or other clade-defined amino acid differences yielded susceptible MICs.

Candida auris is a multidrug resistant yeast, recognized as a cause of invasive infections and health care associated outbreaks around the world. C. auris is of great public health concern, due to its propensity for drug resistance, mode and pace of its transmission, and the possibility that biologic and epidemiologic factors could exacerbate worldwide emergence of C. auris infections. Currently, outbreak response is complicated by limited treatment options and inadequate disinfection strategies, as well as by issues (misidentification, long turnaround time) associated with application of commonly used diagnostic tools. Misdiagnosis of C. auris is common since many diagnostic platforms available in clinical and public health laboratories depend on reference databases that have not fully incorporated C. auris . Moreover, the correlation between minimal inhibitory concentration values (MICs) and clinical outcomes is poorly understood resulting in the absence of C. auris -specific breakpoints. New, accurate and fast diagnostic methods have emerged to facilitate effective patient management and improve infection control measures, ultimately reducing the potential for C. auris transmission. This review provides an overview of available C. auris detection/identification and antifungal susceptibility determination methods and discusses their advantages and limitations. A special emphasis has been placed on culture-independent methods that have recently been developed and offer faster turnaround times.