Abstract
ABSTRACTCandida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality. C. auris strains often demonstrate high fluconazole and amphotericin B MIC values, and some strains are resistant to all three major antifungal classes. We evaluated the susceptibility of 16 C. auris clinical strains, isolated from a wide geographical area, to 10 antifungal agents, including APX001A, a novel agent that inhibits the fungal protein Gwt1 (glycosylphosphatidylinositol-anchored wall transfer protein 1). APX001A demonstrated significantly lower MIC50 and MIC90 values (0.004 and 0.031 μg/ml, respectively) than all other agents tested. The efficacy of the prodrug APX001 was evaluated in an immunocompromised murine model of disseminated C. auris infection. Significant efficacy (80 to 100% survival) was observed in all three APX001 treatment groups versus 50% survival for the anidulafungin treatment group. In addition, APX001 showed a significant log reduction in CFU counts in kidney, lung, and brain tissue (1.03 to 1.83) versus the vehicle control. Anidulafungin also showed a significant log reduction in CFU in the kidneys and lungs (1.5 and 1.62, respectively) but did not impact brain CFU. These data support further clinical evaluation of this new antifungal agent.
Highlights
Candida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality
We evaluated the activities of APX001A and APX001 against a panel of 16 diverse C. auris isolates and in a disseminated candidiasis infection model, respectively
APX001A was highly active against all 16 strains of C. auris with markedly lower MIC50 and MIC90 values than the other tested antifungals with an MIC50 of 0.004 g/ml, an MIC90 of 0.031 g/ml, and a range of values between 0.002 to 0.063 g/ml (Table 1). These values are equal to or lower than those previously observed for the activity of APX001A against other Candida species [14, 16]
Summary
Candida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality. Anidulafungin showed a significant log reduction in CFU in the kidneys and lungs (1.5 and 1.62, respectively) but did not impact brain CFU. These data support further clinical evaluation of this new antifungal agent. C. auris was originally identified in a patient in Japan in 2009 [5] Since it appears to have emerged simultaneously in several countries, resulting in the identification of four distinct clades [2]. International travel has expedited the spread of this species, which has been identified in numerous countries around the globe, including Japan, South Korea, South Africa, Kuwait, Kenya, United Kingdom, India, Pakistan, Colombia, Venezuela, and the United States [2, 6,7,8,9]
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