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      Combined Antifungal Resistance and Biofilm Tolerance: the Global Threat of Candida auris

      review-article

      a , , b

      mSphere

      American Society for Microbiology

      Candida, antifungal resistance, biofilms, tolerance

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          Abstract

          The enigmatic yeast Candida auris has emerged over the last decade and rapidly penetrated our consciousness. The global threat from this multidrug-resistant yeast has generated a call to arms from within the medical mycology community. Over the past decade, our understanding of how this yeast has spread globally, its clinical importance, and how it tolerates and resists antifungal agents has expanded.

          ABSTRACT

          The enigmatic yeast Candida auris has emerged over the last decade and rapidly penetrated our consciousness. The global threat from this multidrug-resistant yeast has generated a call to arms from within the medical mycology community. Over the past decade, our understanding of how this yeast has spread globally, its clinical importance, and how it tolerates and resists antifungal agents has expanded. This review highlights the clinical importance of antifungal resistance in C. auris and explores our current understanding of the mechanisms associated with azole, polyene, and echinocandin resistance. We also discuss the impact of phenotypic tolerance, with particular emphasis on biofilm-mediated resistance, and present new pipelines of antifungal drugs that promise new hope in the management of C. auris infection.

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          Most cited references 55

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          First hospital outbreak of the globally emerging Candida auris in a European hospital

          Background Candida auris is a globally emerging multidrug resistant fungal pathogen causing nosocomial transmission. We report an ongoing outbreak of C. auris in a London cardio-thoracic center between April 2015 and July 2016. This is the first report of C. auris in Europe and the largest outbreak so far. We describe the identification, investigation and implementation of control measures. Methods Data on C. auris case demographics, environmental screening, implementation of infection prevention/control measures, and antifungal susceptibility of patient isolates were prospectively recorded then analysed retrospectively. Speciation of C. auris was performed by MALDI-TOF and typing of outbreak isolates performed by amplified fragment length polymorphism (AFLP). Results This report describes an ongoing outbreak of 50 C. auris cases over the first 16 month (April 2015 to July 2016) within a single Hospital Trust in London. A total of 44 % (n = 22/50) patients developed possible or proven C. auris infection with a candidaemia rate of 18 % (n = 9/50). Environmental sampling showed persistent presence of the yeast around bed space areas. Implementation of strict infection and prevention control measures included: isolation of cases and their contacts, wearing of personal protective clothing by health care workers, screening of patients on affected wards, skin decontamination with chlorhexidine, environmental cleaning with chorine based reagents and hydrogen peroxide vapour. Genotyping with AFLP demonstrated that C. auris isolates from the same geographic region clustered. Conclusion This ongoing outbreak with genotypically closely related C. auris highlights the importance of appropriate species identification and rapid detection of cases in order to contain hospital acquired transmission.
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            The antifungal pipeline: a reality check

             John Perfect (2017)
            Invasive fungal infections are a major medical concern, particularly in immunocompromised patients. In this Review, Perfect discusses the antifungal pipeline, including advances in the currently used drug classes, novel molecular targets, drugs that could be repurposed from other areas and the use of immune-directed therapies.
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              First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia.

              Characterization of a hospital outbreak of Candida auris candidemia that involved 18 critically ill patients in Venezuela.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                mSphere
                mSphere
                msph
                msph
                mSphere
                mSphere
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2379-5042
                31 July 2019
                Jul-Aug 2019
                : 4
                : 4
                Affiliations
                [a ]Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
                [b ]Oral Sciences Research Group, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
                Carnegie Mellon University
                Author notes
                Address correspondence to Gordon Ramage, gordon.ramage@ 123456glasgow.ac.uk .

                Citation Kean R, Ramage G. 2019. Combined antifungal resistance and biofilm tolerance: the global threat of Candida auris. mSphere 4:e00458-19. https://doi.org/10.1128/mSphere.00458-19.

                Article
                mSphere00458-19
                10.1128/mSphere.00458-19
                6669339
                31366705
                5dd4831d-2a3f-4fc8-972c-e6c5449d4464
                Copyright © 2019 Kean and Ramage.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                Page count
                supplementary-material: 1, Figures: 2, Tables: 0, Equations: 0, References: 72, Pages: 10, Words: 7269
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                Minireview
                Therapeutics and Prevention
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                July/August 2019

                candida, antifungal resistance, biofilms, tolerance

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