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Susceptibility

Manogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICs

Maiken Cavling Arendrup, Anuradha Chowdhary, Karin Meinike Jørgensen, Joseph Meletiadis
Maiken Cavling Arendrup
aUnit of Mycology, Statens Serum Institut, Copenhagen, Denmark
bDepartment of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark
cDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Anuradha Chowdhary
dDepartment of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
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Karin Meinike Jørgensen
aUnit of Mycology, Statens Serum Institut, Copenhagen, Denmark
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Joseph Meletiadis
eClinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
fDepartment of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre, Rotterdam, the Netherlands
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DOI: 10.1128/AAC.00656-20
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ABSTRACT

Fosmanogepix is a novel prodrug in a new class of antifungal agents. Manogepix is the active moiety. We evaluated the CLSI and EUCAST MICs of manogepix and eight comparators against Candida auris. CLSI M27-A3 susceptibility testing of manogepix was performed for 122 C. auris isolates and compared to CLSI and EUCAST MICs for manogepix and eight comparators. Differences and agreement were calculated for each compound. Wild-type upper limits (WT-ULs; the upper MIC where the wild-type distribution ends) for manogepix and correlations with other drugs’ MICs were determined. Manogepix MICs (CLSI/EUCAST [mg/liter]) and WT-ULs were as follows: MIC50s, 0.008/0.016; MIC90s, 0.03/0.03; ranges, 0.001 to 0.25/0.001 to 0.125; 97.5% and 99% WT-ULs, 0.03/0.125 and 0.06/0.125, respectively. The manogepix CLSI/EUCAST MIC distributions spanned 9/8 dilutions, respectively. Significant correlation was found for all azoles, particularly fluconazole (r = 0.22 to 0.74, P < 0.05). Isolates with EUCAST manogepix MICs of ≤0.004 had 7.6-/10.2-fold-lower fluconazole CLSI/EUCAST MICs than the remaining isolates that had higher manogepix MICs. The highest essential agreement between CLSI and EUCAST results was observed for manogepix and fluconazole, with a median difference of −1 to 0 2-fold dilutions, 90th percentile absolute difference of 1, and 90 to 92% and 98 to 100% agreement within ±1 and ±2 dilutions. The lowest agreements within ±1 and ±2 dilutions were found for isavuconazole and anidulafungin (44 to 50% and 69 to 76%). The correlation between CLSI and EUCAST manogepix MICs against C. auris was excellent. Differential MICs were found, and these correlated with fluconazole MICs, suggesting that the C. auris population is a mix of wild-type isolates and non-wild-type isolates with low-grade manogepix MIC elevation, probably involving efflux pump expression. However, manogepix was the most potent agent against C. auris in this in vitro study.

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Manogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICs
Maiken Cavling Arendrup, Anuradha Chowdhary, Karin Meinike Jørgensen, Joseph Meletiadis
Antimicrobial Agents and Chemotherapy Sep 2020, 64 (10) e00656-20; DOI: 10.1128/AAC.00656-20

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Manogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICs
Maiken Cavling Arendrup, Anuradha Chowdhary, Karin Meinike Jørgensen, Joseph Meletiadis
Antimicrobial Agents and Chemotherapy Sep 2020, 64 (10) e00656-20; DOI: 10.1128/AAC.00656-20
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KEYWORDS

APX001A
manogepix
fosmanogepix
APX001
candidemia
antifungal susceptibility
EUCAST
CLSI
fluconazole
amphotericin B
echinocandins

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