Correlation of the in vitro antifungal drug susceptibility with the in vivo activity of fluconazole in a murine model of cerebral infection caused by Cryptococcus gattii

Autor(es)

Mendes, F. E. S. ^[1] ; Oliveira, L. V. N. ^[1] ; Faria, E. S. ^[1] ; Alvarenga, D. G. ^[1] ; Pinto, M. R. ^{[2, 3]} ; Taborda, C. P. ^{[2, 3]} ; Soares, B. M. ^[4] ; Cisalpino, P. S. ^[4] ; Santos, D. A. ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Vale do Rio Doce, Fac Ciencias Saude, BR-35020220 Governador Valadares, MG - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Lab Fungos Dimorf Patogen, Dept Microbiol, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Lab Micol Med IMTSP LIM53, Sao Paulo - Brazil

^[4] Univ Fed Minas Gerais, Dept Microbiol, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES; v. 29, n. 12, p. 1525-1532, DEC 2010.
• Citações Web of Science: 12

Resumo

Forty Cryptococcus gattii strains were submitted to antifungal susceptibility testing with fluconazole, itraconazole, amphotericin B and terbinafine. The minimum inhibitory concentration (MIC) ranges were 0.5-64.0 for fluconazole, < 0.015-0.25 for itraconazole, 0.015-0.5 for amphotericin B and 0.062-2.0 for terbinafine. A bioassay for the quantitation of fluconazole in murine brain tissue was developed. Swiss mice received daily injections of the antifungal, and their brains were withdrawn at different times over the 14-day study period. The drug concentrations varied from 12.98 to 44.60 mu g/mL. This assay was used to evaluate the therapy with fluconazole in a model of infection caused by C. gattii. Swiss mice were infected intracranially and treated with fluconazole for 7, 10 or 14 days. The treatment reduced the fungal burden, but an increase in fungal growth was observed on day 14. The MIC for fluconazole against sequential isolates was 16 mu g/mL, except for the isolates obtained from animals treated for 14 days (MIC = 64 mu g/mL). The quantitation of cytokines revealed a predominance of IFN-gamma and IL-12 in the non-treated group and elevation of IL-4 and IL-10 in the treated group. Our data revealed the possibility of acquired resistance during the antifungal drug therapy. (AU)

• Processo FAPESP: 08/56707-7 - Modulação do sistema imune por antígenos de parede celular e exoantígenos de Histoplasma capsulatum e Pseudallescheria boydii
• Beneficiário: Marcia Ribeiro Pinto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 08/04289-7 - Desenvolvimento, caracterização, terapia antifúngica e imunização de modelo hiporresponsivo de paracoccidioidomicose experimental.
• Beneficiário: Daniel de Assis Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado