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

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  3. Implications of the EUCAST Trailing Phenomenon in Candida tropicalis for the In Vivo Susceptibility in Invertebrate and Murine Models

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  • M C Arendrup
  • J Meletiadis
  • O Zaragoza
  • K M Jørgensen
  • L J Marcos-Zambrano
  • L Kanioura
  • M Cuenca-Estrella
  • J W Mouton
  • J Guinea
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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 languageEnglish
JournalClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Volume24
Issue number11
Pages (from-to)1200-1204
Number of pages5
ISSN1198-743X
DOIs
Publication statusPublished - Nov 2018

    Research areas

  • Antifungal Agents/pharmacology, Candida/drug effects, Candidiasis/microbiology, Drug Resistance, Fungal, Humans, Microbial Sensitivity Tests

ID: 56271240