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.

  • Identification data

    Identifier: imarina:5127738
    Authors:
    Ferna?dez-Silva FLackner MCapilla JMayayo ESutton DCastanheira MFothergill ALass-Flörl CGuarro J
    Abstract:
    It has been argued that the in vitro activity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatment in vivo. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of the FKS1 and FKS2 genes in 17 Candida glabrata strains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs for CSP of <= 0.5 mu g/ml, but they were present in eight of the nine strains with MICs of >= 1 mu g/ml, i.e., three in the FKS1 gene and five in the FKS2 gene. CSP was effective for treating mice infected with strains with MICs of <= 0.5 mu g/ml, showed variable efficacy in animals challenged with strains with MICs of 1 mu g/ml, and did not work in those with strains with MICs of 1 mu g/ml. In addition, mutations, including one reported for the first time, were found outside the HS1 region in the FKS2 gene of six strains with different MICs, but their presence did not influence drug efficacy. The in vitro activity of CSP was compared with that of another echinocandin, anidulafungin, suggesting that the MICs of both drugs, as well as mutations in the HS1 regions of the FKS1 and FKS2 genes, are predictive of outcome.
  • Others:

    Author, as appears in the article.: Ferna?dez-Silva F; Lackner M; Capilla J; Mayayo E; Sutton D; Castanheira M; Fothergill A; Lass-Flörl C; Guarro J
    Department: Ciències Mèdiques Bàsiques
    URV's Author/s: Capilla Luque, Javier / FERNÁNDEZ SILVA, FABIOLA VANESSA / Guarro Artigas, Josep / Mayayo Artal, Emilio Manuel
    Keywords: Therapy Surveillance Resistance Micafungin Management Liposomal amphotericin-b Identification Epidemiology Echinocandin Candida glabrata Anidulafungin
    Abstract: It has been argued that the in vitro activity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatment in vivo. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of the FKS1 and FKS2 genes in 17 Candida glabrata strains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs for CSP of <= 0.5 mu g/ml, but they were present in eight of the nine strains with MICs of >= 1 mu g/ml, i.e., three in the FKS1 gene and five in the FKS2 gene. CSP was effective for treating mice infected with strains with MICs of <= 0.5 mu g/ml, showed variable efficacy in animals challenged with strains with MICs of 1 mu g/ml, and did not work in those with strains with MICs of 1 mu g/ml. In addition, mutations, including one reported for the first time, were found outside the HS1 region in the FKS2 gene of six strains with different MICs, but their presence did not influence drug efficacy. The in vitro activity of CSP was compared with that of another echinocandin, anidulafungin, suggesting that the MICs of both drugs, as well as mutations in the HS1 regions of the FKS1 and FKS2 genes, are predictive of outcome.
    Thematic Areas: Saúde coletiva Química Pharmacology (medical) Pharmacology & pharmacy Pharmacology Odontología Nutrição Microbiology Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Infectious diseases Farmacia Ensino Engenharias iv Engenharias iii Engenharias ii Enfermagem Educação física Educação Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência de alimentos Biotecnología Biodiversidade Astronomia / física
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: javier.capilla@urv.cat
    Author identifier: 0000-0002-0765-6403
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://journals.asm.org/doi/10.1128/aac.02666-13
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Antimicrobial Agents And Chemotherapy. 58 (7): 3646-3649
    APA: Ferna?dez-Silva F; Lackner M; Capilla J; Mayayo E; Sutton D; Castanheira M; Fothergill A; Lass-Flörl C; Guarro J (2014). 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.. Antimicrobial Agents And Chemotherapy, 58(7), 3646-3649. DOI: 10.1128/AAC.02666-13
    Article's DOI: 10.1128/AAC.02666-13
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2014
    Publication Type: Journal Publications
  • Keywords:

    Infectious Diseases,Microbiology,Pharmacology,Pharmacology & Pharmacy,Pharmacology (Medical)
    Therapy
    Surveillance
    Resistance
    Micafungin
    Management
    Liposomal amphotericin-b
    Identification
    Epidemiology
    Echinocandin
    Candida glabrata
    Anidulafungin
    Saúde coletiva
    Química
    Pharmacology (medical)
    Pharmacology & pharmacy
    Pharmacology
    Odontología
    Nutrição
    Microbiology
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Matemática / probabilidade e estatística
    Interdisciplinar
    Infectious diseases
    Farmacia
    Ensino
    Engenharias iv
    Engenharias iii
    Engenharias ii
    Enfermagem
    Educação física
    Educação
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências agrárias i
    Ciência de alimentos
    Biotecnología
    Biodiversidade
    Astronomia / física
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