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Resistance to echinocandin antifungal agents in the United Kingdom in clinical isolates of Candida glabrata: Fifteen years of interpretation and assessment

Fraser, Mark; Borman, Andrew M.; Thorn, Robin; Lawrance, Lynne M.

Authors

Mark Fraser

Andrew M. Borman

Robin Thorn Robin2.Thorn@uwe.ac.uk
Associate Professor Molecular Life Sciences

Lynne Lawrance Lynne.Lawrance@uwe.ac.uk
Senior Lecturer in Medical Microbiology



Abstract

Candidaemia is widely reported as the fourth most common form of bloodstream infection worldwide. Reports of breakthrough cases of candidaemia are increasing, especially in the context of a move away from azole antifungals as prophylactic or first line treatment towards the use of echinocandin agents. The global evaluation of echinocandin antifungal susceptibility since 2003 has included switches in testing methodologies and the move to a sentinel echinocandin approach for classification reporting. This study compiles previously unpublished data from echinocandin susceptibility testing of UK clinical isolates of C. glabrata received at the Public Health England Mycology Reference Laboratory from 2003 to 2016, and re-evaluates the prevalence of resistance in light of currently accepted testing protocols. From 2015 onwards, FKS gene mutation detection using a novel Pyrosequencing® assay was assessed as a predictor of echinocandin resistance alongside conventional susceptibility testing.
Overall, our data show that echinocandin resistance in UK isolates of C. glabrata is a rare phenomenon and prevalence has not appreciably increased in the last 14 years. The pyrosequencing assay was able to successfully detect hot spot mutations in FKS1 and FKS2, although not all isolates that exhibited phenotypic resistance demonstrated detectable hot spot mutations. We propose that a rapid genomic based detection method for FKS mutations, as part of a multifactorial approach to susceptibility testing, could help provide accurate and timely management decisions especially in regions where echinocandin resistance has been reported to be emerging in this important pathogen.

Journal Article Type Article
Publication Date Feb 1, 2020
Journal Medical Mycology
Print ISSN 1369-3786
Electronic ISSN 1460-2709
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 58
Issue 2
Article Number myz053
Pages 219-226
APA6 Citation Fraser, M., Borman, A. M., Thorn, R., & Lawrance, L. M. (2020). Resistance to echinocandin antifungal agents in the United Kingdom in clinical isolates of Candida glabrata: Fifteen years of interpretation and assessment. Medical Mycology, 58(2), 219-226. https://doi.org/10.1093/mmy/myz053
DOI https://doi.org/10.1093/mmy/myz053
Keywords Candida glabrata, FKS, resistance, echinocandin, pyrosequencing
Publisher URL https://academic.oup.com/journals

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Copyright Statement
This is a pre-copyedited, author-produced version of an article accepted for publication in [insert journal title] following peer review. The version of record Mark Fraser, Andrew M Borman, Robin Thorn, Lynne M Lawrance, Resistance to echinocandin antifungal agents in the United Kingdom in clinical isolates of Candida glabrata: Fifteen years of interpretation and assessment, Medical Mycology, , myz053 is available online at: https://doi.org/10.1093/mmy/myz053.







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