Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method

M. C. Arendrup; J. Meletiadis; O. Zaragoza; K. M. Jørgensen; L. J. Marcos-Zambrano; L. Kanioura; M. Cuenca-Estrella; J. W. Mouton; J. Guinea

doi:10.1016/j.cmi.2018.02.021

Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method

M. C. Arendrup^*, J. Meletiadis, O. Zaragoza, K. M. Jørgensen, L. J. Marcos-Zambrano, L. Kanioura, M. Cuenca-Estrella, J. W. Mouton, J. Guinea

^*Corresponding author for this work

Department of Clinical Medicine

14 Citations (Scopus)

Abstract

Objectives: Rezafungin (CD101) is a new long-acting echinocandin allowing weekly dosing, currently undergoing phase-II clinical trials for invasive candidiasis. The aim of this study was to assess rezafungin's in vitro activity against the most frequent Candida species following the EUCAST methodology. Methods: The susceptibility of 2018 clinical Candida isolates was determined at four European laboratories. In parallel, six control strains were repeatedly tested. Wild-type upper limits (WT-ULs), defined as the MIC value where the wild-type distribution ends, were determined following the principles for EUCAST ECOFF-setting. Results: The lowest rezafungin MICs (geometric MIC (GM-MIC), MIC range (mg/L)) were observed for C. albicans (0.016, 0.002–0.125) and the highest for C. parapsilosis (1.657, 0.063->4). MICs for the remaining species were in between these values (GM-MICs 0.048–0.055). Visual and statistical WT-ULs were identical for C. glabrata (0.125), C. krusei (0.125), C. parapsilosis (4), and C. tropicalis (0.25). If adopting these WT-ULs for classification into WT and non-WT populations, 1/413 C. glabrata, 1/402 C. krusei, 1/398 C. parapsilosis, and 1/402 C. tropicalis isolates were categorized as non-WT, all of which derived from Laboratory 1. For C. albicans unexplained laboratory variation was observed (WT-UL: 0.063–0.125 in Laboratories 1 and 2 versus 0.016 in Laboratories 3 and 4). A similar systematic difference was observed comparing the MICs for the three C. albicans QC strains, specifically, obtained in Laboratories 1and 2 with those in Laboratories 3 and 4. Discussion: Rezafungin displayed species-specific activity similar to other echinocandins. Interlaboratory variation was observed for the most susceptible species C. albicans clinical and QC strains, an observation that warrants further investigation.

Original language	English
Journal	Clinical Microbiology and Infection
Volume	24
Issue number	11
Pages (from-to)	1200-1204
Number of pages	5
ISSN	1198-743X
DOIs	https://doi.org/10.1016/j.cmi.2018.02.021
Publication status	Published - 2018

Keywords

Antifungal susceptibility
Candida
CD101
Echinocandin
EUCAST

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10.1016/j.cmi.2018.02.021

http://www.clinicalmicrobiologyandinfection.com/article/S1198743X18301964/pdf

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@article{edd0b8b9f6f842a68aae03b253a2d06a,

title = "Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method",

abstract = "Objectives: Rezafungin (CD101) is a new long-acting echinocandin allowing weekly dosing, currently undergoing phase-II clinical trials for invasive candidiasis. The aim of this study was to assess rezafungin's in vitro activity against the most frequent Candida species following the EUCAST methodology. Methods: The susceptibility of 2018 clinical Candida isolates was determined at four European laboratories. In parallel, six control strains were repeatedly tested. Wild-type upper limits (WT-ULs), defined as the MIC value where the wild-type distribution ends, were determined following the principles for EUCAST ECOFF-setting. Results: The lowest rezafungin MICs (geometric MIC (GM-MIC), MIC range (mg/L)) were observed for C. albicans (0.016, 0.002–0.125) and the highest for C. parapsilosis (1.657, 0.063->4). MICs for the remaining species were in between these values (GM-MICs 0.048–0.055). Visual and statistical WT-ULs were identical for C. glabrata (0.125), C. krusei (0.125), C. parapsilosis (4), and C. tropicalis (0.25). If adopting these WT-ULs for classification into WT and non-WT populations, 1/413 C. glabrata, 1/402 C. krusei, 1/398 C. parapsilosis, and 1/402 C. tropicalis isolates were categorized as non-WT, all of which derived from Laboratory 1. For C. albicans unexplained laboratory variation was observed (WT-UL: 0.063–0.125 in Laboratories 1 and 2 versus 0.016 in Laboratories 3 and 4). A similar systematic difference was observed comparing the MICs for the three C. albicans QC strains, specifically, obtained in Laboratories 1and 2 with those in Laboratories 3 and 4. Discussion: Rezafungin displayed species-specific activity similar to other echinocandins. Interlaboratory variation was observed for the most susceptible species C. albicans clinical and QC strains, an observation that warrants further investigation.",

keywords = "Antifungal susceptibility, Candida, CD101, Echinocandin, EUCAST",

author = "Arendrup, {M. C.} and J. Meletiadis and O. Zaragoza and J{\o}rgensen, {K. M.} and Marcos-Zambrano, {L. J.} and L. Kanioura and M. Cuenca-Estrella and Mouton, {J. W.} and J. Guinea",

year = "2018",

doi = "10.1016/j.cmi.2018.02.021",

language = "English",

volume = "24",

pages = "1200--1204",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

publisher = "Elsevier",

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TY - JOUR

T1 - Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method

AU - Arendrup, M. C.

AU - Meletiadis, J.

AU - Zaragoza, O.

AU - Jørgensen, K. M.

AU - Marcos-Zambrano, L. J.

AU - Kanioura, L.

AU - Cuenca-Estrella, M.

AU - Mouton, J. W.

AU - Guinea, J.

PY - 2018

Y1 - 2018

N2 - Objectives: Rezafungin (CD101) is a new long-acting echinocandin allowing weekly dosing, currently undergoing phase-II clinical trials for invasive candidiasis. The aim of this study was to assess rezafungin's in vitro activity against the most frequent Candida species following the EUCAST methodology. Methods: The susceptibility of 2018 clinical Candida isolates was determined at four European laboratories. In parallel, six control strains were repeatedly tested. Wild-type upper limits (WT-ULs), defined as the MIC value where the wild-type distribution ends, were determined following the principles for EUCAST ECOFF-setting. Results: The lowest rezafungin MICs (geometric MIC (GM-MIC), MIC range (mg/L)) were observed for C. albicans (0.016, 0.002–0.125) and the highest for C. parapsilosis (1.657, 0.063->4). MICs for the remaining species were in between these values (GM-MICs 0.048–0.055). Visual and statistical WT-ULs were identical for C. glabrata (0.125), C. krusei (0.125), C. parapsilosis (4), and C. tropicalis (0.25). If adopting these WT-ULs for classification into WT and non-WT populations, 1/413 C. glabrata, 1/402 C. krusei, 1/398 C. parapsilosis, and 1/402 C. tropicalis isolates were categorized as non-WT, all of which derived from Laboratory 1. For C. albicans unexplained laboratory variation was observed (WT-UL: 0.063–0.125 in Laboratories 1 and 2 versus 0.016 in Laboratories 3 and 4). A similar systematic difference was observed comparing the MICs for the three C. albicans QC strains, specifically, obtained in Laboratories 1and 2 with those in Laboratories 3 and 4. Discussion: Rezafungin displayed species-specific activity similar to other echinocandins. Interlaboratory variation was observed for the most susceptible species C. albicans clinical and QC strains, an observation that warrants further investigation.

AB - Objectives: Rezafungin (CD101) is a new long-acting echinocandin allowing weekly dosing, currently undergoing phase-II clinical trials for invasive candidiasis. The aim of this study was to assess rezafungin's in vitro activity against the most frequent Candida species following the EUCAST methodology. Methods: The susceptibility of 2018 clinical Candida isolates was determined at four European laboratories. In parallel, six control strains were repeatedly tested. Wild-type upper limits (WT-ULs), defined as the MIC value where the wild-type distribution ends, were determined following the principles for EUCAST ECOFF-setting. Results: The lowest rezafungin MICs (geometric MIC (GM-MIC), MIC range (mg/L)) were observed for C. albicans (0.016, 0.002–0.125) and the highest for C. parapsilosis (1.657, 0.063->4). MICs for the remaining species were in between these values (GM-MICs 0.048–0.055). Visual and statistical WT-ULs were identical for C. glabrata (0.125), C. krusei (0.125), C. parapsilosis (4), and C. tropicalis (0.25). If adopting these WT-ULs for classification into WT and non-WT populations, 1/413 C. glabrata, 1/402 C. krusei, 1/398 C. parapsilosis, and 1/402 C. tropicalis isolates were categorized as non-WT, all of which derived from Laboratory 1. For C. albicans unexplained laboratory variation was observed (WT-UL: 0.063–0.125 in Laboratories 1 and 2 versus 0.016 in Laboratories 3 and 4). A similar systematic difference was observed comparing the MICs for the three C. albicans QC strains, specifically, obtained in Laboratories 1and 2 with those in Laboratories 3 and 4. Discussion: Rezafungin displayed species-specific activity similar to other echinocandins. Interlaboratory variation was observed for the most susceptible species C. albicans clinical and QC strains, an observation that warrants further investigation.

KW - Antifungal susceptibility

KW - Candida

KW - CD101

KW - Echinocandin

KW - EUCAST

U2 - 10.1016/j.cmi.2018.02.021

DO - 10.1016/j.cmi.2018.02.021

M3 - Journal article

C2 - 29505881

AN - SCOPUS:85045057913

SN - 1198-743X

VL - 24

SP - 1200

EP - 1204

JO - Clinical Microbiology and Infection

JF - Clinical Microbiology and Infection

IS - 11

ER -

Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method

Abstract

Keywords

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