OPEN Antimicrobial agents and chemotherapy | 10 Jan 2018
CL Hager, EL Larkin, L Long, FZ Abidi, KJ Shaw and MA Ghannoum
Candida 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 minimum inhibitory concentration values, and some strains are resistant to all 3 major antifungal classes. Here 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 (GPI-anchored wall transfer protein 1). APX001A demonstrated significantly lower MIC50 and MIC90 values (0.004 μg/mL 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%-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 colony forming units (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 kidney and lung (1.5 and 1.62, respectively), but did not impact brain CFU. These data support further clinical evaluation of this new antifungal agent.
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