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Susceptibility

In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak

YanChun Zhu, Shannon Kilburn, Mili Kapoor, Sudha Chaturvedi, Karen Joy Shaw, Vishnu Chaturvedi
YanChun Zhu
aMycology Laboratory, Wadsworth Center, New York State Department of Health, Albany, New York, USA
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Shannon Kilburn
aMycology Laboratory, Wadsworth Center, New York State Department of Health, Albany, New York, USA
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Mili Kapoor
cAmplyx Pharmaceuticals, San Diego, California, USA
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Sudha Chaturvedi
aMycology Laboratory, Wadsworth Center, New York State Department of Health, Albany, New York, USA
bDepartment of Biomedical Sciences, University at Albany School of Public Health, Albany, New York, USA
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Karen Joy Shaw
dHearts Consulting Group, Poway, California, USA
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Vishnu Chaturvedi
aMycology Laboratory, Wadsworth Center, New York State Department of Health, Albany, New York, USA
bDepartment of Biomedical Sciences, University at Albany School of Public Health, Albany, New York, USA
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  • ORCID record for Vishnu Chaturvedi
DOI: 10.1128/AAC.01124-20
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ABSTRACT

An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several isolates are panresistant. Thus, there is an urgent need for new drugs with a novel mechanism of action to combat the resistance challenge. Manogepix (MGX) is a first-in-class agent that targets the fungal Gwt1 enzyme. The prodrug fosmanogepix is currently in phase 2 clinical development for the treatment of fungal infections. We evaluated the susceptibility of 200 New York C. auris isolates to MGX and 10 comparator drugs using CLSI methodology. MGX demonstrated lower MICs than comparators (MIC50 and MIC90, 0.03 mg/liter; range, 0.004 to 0.06 mg/liter). The local epidemiological cutoff value (ECV) for MGX indicated all C. auris isolates were within the population of wild-type (WT) strains; 0.06 mg/liter defines the upper limit of wild type (UL-WT). MGX was 8- to 32-fold more active than the echinocandins, 16- to 64-fold more active than the azoles, and 64-fold more active than amphotericin B. No differences were found in the MGX or comparators’ MIC50, MIC90, or geometric mean (GM) values when subsets of clinical, surveillance, and environmental isolates were evaluated. The range of MGX MIC values for six C. auris panresistant isolates was 0.008 to 0.015 mg/liter, and the median and mode MIC values were 0.015 mg/liter, demonstrating that MGX retains activity against these isolates. These data support further clinical evaluation of fosmanogepix for the treatment of C. auris infections, including highly resistant isolates.

FOOTNOTES

    • Received 2 June 2020.
    • Returned for modification 2 August 2020.
    • Accepted 18 August 2020.
    • Accepted manuscript posted online 24 August 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak
YanChun Zhu, Shannon Kilburn, Mili Kapoor, Sudha Chaturvedi, Karen Joy Shaw, Vishnu Chaturvedi
Antimicrobial Agents and Chemotherapy Oct 2020, 64 (11) e01124-20; DOI: 10.1128/AAC.01124-20

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In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak
YanChun Zhu, Shannon Kilburn, Mili Kapoor, Sudha Chaturvedi, Karen Joy Shaw, Vishnu Chaturvedi
Antimicrobial Agents and Chemotherapy Oct 2020, 64 (11) e01124-20; DOI: 10.1128/AAC.01124-20
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KEYWORDS

APX001
fosmanogepix
APX001A
manogepix
Gwt1
antifungal
Candida auris
resistance

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