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      Rapid emergence of FKS mutations in Candida glabrata isolates in a peritoneal candidiasis

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          Abstract

          We report a rapid acquisition of echinocandin resistance after 12 days of micafungin treatment, without prior exposure, in a patient with peritoneal candidiasis due to C. glabrata. Isolates recovered before and after treatment were compared by multilocus sequence typing. Results of antifungal susceptibility testing and FKS mutations were reported. The interest of repeating antifungal susceptibility testing for echinocandin molecules during the treatment is discussed and a strategy to research FKS mutations proposed.

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          Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012.

          Antifungal susceptibility testing of Candida has been standardized and refined and now may play a useful role in managing Candida infections. Important new developments include validation of 24-h reading times for all antifungal agents and the establishment of species-specific epidemiological cutoff values (ECVs) for the systemically active antifungal agents and both common and uncommon species of Candida. The clinical breakpoints (CBPs) for fluconazole, voriconazole, and the echinocandins have been revised to provide species-specific interpretive criteria for the six most common species. The revised CBPs not only are predictive of clinical outcome but also provide a more sensitive means of identifying those strains with acquired or mutational resistance mechanisms. This brief review serves as an update on the new developments in the antifungal susceptibility testing of Candida spp. using Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) methods.
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            Echinocandin resistance: an emerging clinical problem?

            Echinocandin resistance in Candida is a great concern, as the echinocandin drugs are recommended as first-line therapy for patients with invasive candidiasis. Here, we review recent advances in our understanding of the epidemiology, underlying mechanisms, methods for detection and clinical implications.
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              FKS mutations and elevated echinocandin MIC values among Candida glabrata isolates from U.S. population-based surveillance.

              Candida glabrata is the second leading cause of candidemia in the United States. Its high-level resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance study for elevated echinocandin MIC values (MICs of ≥0.25 μg/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) for one or more of the echinocandin drugs caspofungin, anidulafungin, and micafungin. All of the isolates with elevated MIC values had a mutation in the previously identified hot spot 1 of either the glucan synthase FKS1 (n = 2) or FKS2 (n = 14) gene. No mutations were detected in hot spot 2 of either FKS1 or FKS2. The predominant mutation was mutation of FKS2-encoded serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G for FKS1 and R665G for FKS2, have not been reported previously for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations.
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                Author and article information

                Contributors
                Journal
                Med Mycol Case Rep
                Med Mycol Case Rep
                Medical Mycology Case Reports
                Elsevier
                2211-7539
                25 April 2017
                June 2017
                25 April 2017
                : 16
                : 28-30
                Affiliations
                [a ]Laboratoire de Parasitologie-Mycologie, Centre Hospitalo-universitaire de Nîmes, Nîmes, France
                [b ]Service de réanimation chirurgicale, Centre Hospitalo-universitaire de Nîmes, Nîmes, France
                [c ]Département de Parasitologie-Mycologie, Centre Hospitalo-universitaire de Montpellier, France
                Author notes
                Article
                S2211-7539(17)30017-9
                10.1016/j.mmcr.2017.04.004
                5413194
                28491490
                a4fb8baf-e74a-47f4-8ae3-a19f2d34bcf6
                © 2017 Published by Elsevier B.V. on behalf of International Society for Human and Animal Mycology.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 8 March 2017
                : 7 April 2017
                : 24 April 2017
                Categories
                Case Report

                echinocandin resistance,candida glabrata,antifungal susceptibility testing,fks mutations,mic interpretation

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