How Yeast Antifungal Resistance Gene Analysis Is Essential to Validate Antifungal Susceptibility Testing Systems.

Details

Ressource 1Download: fcimb-12-859439.pdf (3926.18 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CC99145B5F54
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
How Yeast Antifungal Resistance Gene Analysis Is Essential to Validate Antifungal Susceptibility Testing Systems.
Journal
Frontiers in cellular and infection microbiology
Author(s)
Pellaton N., Sanglard D., Lamoth F., Coste A.T.
ISSN
2235-2988 (Electronic)
ISSN-L
2235-2988
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
12
Pages
859439
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The antifungal susceptibility testing (AFST) of yeast pathogen alerts clinicians about the potential emergence of resistance. In this study, we compared two commercial microdilution AFST methods: Sensititre YeastOne read visually (YO) and MICRONAUT-AM read visually (MN) or spectrophotometrically (MNV), interpreted with Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing criteria, respectively.
Overall, 97 strains from 19 yeast species were measured for nine antifungal drugs including a total of 873 observations. First, the minimal inhibitory concentration (MIC) was compared between YO and MNV, and between MNV and MN, either directly or by assigning them to five susceptibility categories. Those categories were based on the number of MIC dilutions around the breakpoint or epidemiological cut-off reference values (ECOFFs or ECVs). Second, YO and MNV methods were evaluated for their ability to detect the elevation of MICs due to mutation in antifungal resistance genes, thanks to pairs or triplets of isogenic strains isolated from a single patient along a treatment previously analyzed for antifungal resistance gene mutations. Reproducibility measurement was evaluated, thanks to three quality control (QC) strains.
YO and MNV direct MIC comparisons obtained a global agreement of 67%. Performing susceptibility category comparisons, only 22% and 49% of the MICs could be assigned to categories using breakpoints and ECOFFs/ECVs, respectively, and 40% could not be assigned due to the lack of criteria in both consortia. The YO and MN susceptibility categories gave accuracies as low as 50%, revealing the difficulty to implement this method of comparison. In contrast, using the antifungal resistance gene sequences as a gold standard, we demonstrated that both methods (YO and MN) were equally able to detect the acquisition of resistance in the Candida strains, even if MN showed a global lower MIC elevation than YO. Finally, no major differences in reproducibility were observed between the three AFST methods.
This study demonstrates the valuable use of both commercial microdilution AFST methods to detect antifungal resistance due to point mutations in antifungal resistance genes. We highlighted the difficulty to conduct conclusive analyses without antifungal gene sequence data as a gold standard. Indeed, MIC comparisons taking into account the consortia criteria of interpretation remain difficult even after the effort of harmonization.
Keywords
Antifungal Agents/pharmacology, Candida, Drug Resistance, Fungal/genetics, Humans, Microbial Sensitivity Tests, Reproducibility of Results, Yeasts, CLSI, EUCAST, MICRONAUT-AM, Sensititre TM YeastOne TM, antifungal susceptibility, diagnostic test, resistance genes
Pubmed
Web of science
Open Access
Yes
Create date
31/05/2022 11:31
Last modification date
03/08/2022 7:13
Usage data