Articles producció científica> Ciències Mèdiques Bàsiques

In Vitro Antifungal Susceptibility of Candida glabrata to Caspofungin and the Presence of FKS Mutations Correlate with Treatment Response in an Immunocompromised Murine Model of Invasive Infection

  • Datos identificativos

    Identificador: PC:51
    Autores:
    Fabiola Fernández-SilvaMichaela LacknerJavier CapillaEmilio MayayoDeanna SuttonMariana CastanheiraAnnette W Fothergill
    Resumen:
    It has been argued that in vitro activity of caspofungin (CSP) is not a good predictor of the in vivo outcome of echinocandins treatment. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of FKS1 and FKS2 genes of 17 Candida glabrata strains with a wide MICs range. The efficacy of CSP against systemic infections by all those strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs of CSP ≤ 0.5 μg/ml, but they were present in eight of the nine strains with MICs ≥ 1 μg/ml, i.e. three in the FKS1 and five in the FKS2 genes. CSP was effective to treat mice infected with strains with MICs ≤ 0.5μg/ml, showed variable efficacy in animals challenged with strains with MICs = 1μg/ml and did not work in those with strains with MICs > 1μg/ml. In addition, mutations outside the HS1 region were found in the FKS 2 gene of six strains with different MICs, including a first time reported mutation, but their presence did not influence the drug efficacy. In vitro activity of CSP was compared with other echinocandin i.e., anidulafungin suggesting that MICs of both drugs as well as mutations in the HS1 regions of FKS1 or FKS2 genes are predictive of the outcome.
  • Otros:

    Autor según el artículo: Fabiola Fernández-Silva Michaela Lackner Javier Capilla Emilio Mayayo Deanna Sutton Mariana Castanheira Annette W Fothergill
    Departamento: Ciències Mèdiques Bàsiques
    e-ISSN: 1098-6596
    Autor/es de la URV: Fernández Silva, Fabiola Vanessa Michaela Lackner Capilla Luque, Javier Mayayo Artal , Emilio Manuel Deanna Sutton Mariana Castanheira Annette W Fothergill Cornelia Lass-Flörl Guarro Artigas , Josep
    Palabras clave: Candida glabrata Candida glabrata Candida glabrata
    Resumen: It has been argued that in vitro activity of caspofungin (CSP) is not a good predictor of the in vivo outcome of echinocandins treatment. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of FKS1 and FKS2 genes of 17 Candida glabrata strains with a wide MICs range. The efficacy of CSP against systemic infections by all those strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs of CSP ≤ 0.5 μg/ml, but they were present in eight of the nine strains with MICs ≥ 1 μg/ml, i.e. three in the FKS1 and five in the FKS2 genes. CSP was effective to treat mice infected with strains with MICs ≤ 0.5μg/ml, showed variable efficacy in animals challenged with strains with MICs = 1μg/ml and did not work in those with strains with MICs > 1μg/ml. In addition, mutations outside the HS1 region were found in the FKS 2 gene of six strains with different MICs, including a first time reported mutation, but their presence did not influence the drug efficacy. In vitro activity of CSP was compared with other echinocandin i.e., anidulafungin suggesting that MICs of both drugs as well as mutations in the HS1 regions of FKS1 or FKS2 genes are predictive of the outcome.
    Grupo de investigación: Unitat de Micologia i Microbiologia Ambiental
    Acceso a la licencia de uso: thttps://creativecommons.org/licenses/by/3.0/es/
    ISSN: 0066-4804
    Identificador del autor: N/A N/A N/A N/A N/A N/A N/A N/A N/A
    Fecha de alta del registro: 2014-05-14
    Página final: 3649
    Volumen de revista: 58
    Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
    Enlace a la fuente original: https://aac.asm.org/content/58/7/3646.long
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI del artículo: 10.1128/AAC.02666-13
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2014
    Página inicial: 3646
    Tipo de publicación: Article Artículo Article
  • Palabras clave:

    Fongs patògens
    Candida glabrata
    Candida glabrata
    Candida glabrata
    0066-4804
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