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