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
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2010
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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 Swiss mice received daily injections of the antifungal, and their brains were withdrawn at different times over the 14-day study period.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. Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)[APQ-2864-07] Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2008/04289-7] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2008/56707-7] Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) |
Identificador |
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES, v.29, n.12, p.1525-1532, 2010 0934-9723 http://producao.usp.br/handle/BDPI/28667 10.1007/s10096-010-1034-8 |
Idioma(s) |
eng |
Publicador |
SPRINGER |
Relação |
European Journal of Clinical Microbiology & Infectious Diseases |
Direitos |
restrictedAccess Copyright SPRINGER |
Palavras-Chave | #TRANSPORTER-ENCODING GENE #MICROBIOLOGICAL ASSAY #LIQUID-CHROMATOGRAPHY #COMBINATION THERAPY #AMPHOTERICIN-B #NEOFORMANS #MENINGITIS #RESISTANCE #CAPSULES #BIOEQUIVALENCE #Infectious Diseases #Microbiology |
Tipo |
article original article publishedVersion |