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Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e02319-17. doi: 10.1128/AAC.02319-17. Print 2018 Mar.

In Vitro and In Vivo Evaluation of the Antifungal Activity of APX001A/APX001 against Candida auris.

Author information

1
Center for Medical Mycology, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
2
Amplyx Pharmaceuticals, San Diego, California, USA.
3
Center for Medical Mycology, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, Ohio, USA mahmoud.ghannoum@case.edu.
#
Contributed equally

Abstract

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 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.

KEYWORDS:

APX001; APX001A; Candida auris; antifungal susceptibility testing; brain penetration; efficacy; infection model; survival; susceptibility testing; yeast

PMID:
29311065
PMCID:
PMC5826120
DOI:
10.1128/AAC.02319-17
[Indexed for MEDLINE]
Free PMC Article

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