A murine model of Cryptococcus gattii meningoencephalitis.

Objectives: Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neofor...

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Publicado en:Journal of Antimicrobial Chemotherapy (JAC) Vol. 67; no. 6; pp. 1432 - 1439
Autores principales: Thompson GR 3rd, Wiederhold NP, Najvar LK, Bocanegra R, Kirkpatrick WR, Graybill JR, Patterson TF, Thompson, George R 3rd, Wiederhold, Nathan P, Najvar, Laura K, Bocanegra, Rosie, Kirkpatrick, William R, Graybill, John R, Patterson, Thomas F
Formato: research Journal Article
Publicado: Oxford University Press / USA Jun2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2012
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      pub: Oxford University Press / USA
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        atl: A murine model of Cryptococcus gattii meningoencephalitis.
      aug:
        au:
          Thompson GR 3rd
          Wiederhold NP
          Najvar LK
          Bocanegra R
          Kirkpatrick WR
          Graybill JR
          Patterson TF
          Thompson, George R 3rd
          Wiederhold, Nathan P
          Najvar, Laura K
          Bocanegra, Rosie
          Kirkpatrick, William R
          Graybill, John R
          Patterson, Thomas F
        affil: Department of Medical Microbiology and Immunology and Department of Internal Medicine the Division of Infectious Diseases, The University of California Davis, Davis, CA, USA
      sug:
        subj:
          Cryptococcosis Microbiology
          Cryptococcosis Pathology
          Cryptococcus
          Meningoencephalitis Microbiology
          Meningoencephalitis Pathology
          Models, Biological
          Animal Studies
          Antifungal Agents Administration and Dosage
          Antigens, Fungal Blood
          Brain Microbiology
          Colony Count, Microbial
          Cryptococcosis Drug Therapy
          Fluconazole Administration and Dosage
          Heterocyclic Compounds Administration and Dosage
          Histocytochemistry
          Meningoencephalitis Drug Therapy
          Mice
          Survival Analysis
      ab: Objectives: Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by C. gattii.Methods: Mice were inoculated intracranially with either C. gattii (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii infecting inocula were compared with a fixed inoculum of C. neoformans, and differences were assessed by survival, brain tissue fungal burden, serum antigen titres and histopathological changes within brain tissue. For treatment, fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post-inoculation.Results: C. gattii was more virulent than C. neoformans, as evident by shorter median survival, earlier histopathological changes and higher serum antigen titres. However, no differences in fungal burden or dissemination to other organs were observed among the various groups. In treatment studies, both fluconazole and posaconazole improved the median survival of mice infected with either species. However, neither regimen improved the percentage of animals surviving to the predetermined study endpoint.Conclusions: These results demonstrate the virulence of C. gattii meningoencephalitis and the potential of this model for the assessment of new treatment strategies.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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