Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | dks060 |
| Pages (from-to) | 1432-1438 |
| Number of pages | 7 |
| Journal | Journal of Antimicrobial Chemotherapy |
| Volume | 67 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2012 |
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Keywords
- C. gattii
- Cryptococcal meningoencephalitis
- Cryptococcus neoformans
- Fluconazole
- Posaconazole
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
Cite this
A murine model of Cryptococcus gattii meningoencephalitis. / Thompson, George Richard; Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Graybill, John R.; Patterson, Thomas F.
In: Journal of Antimicrobial Chemotherapy, Vol. 67, No. 6, dks060, 06.2012, p. 1432-1438.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A murine model of Cryptococcus gattii meningoencephalitis
AU - Thompson, George Richard
AU - Wiederhold, Nathan P.
AU - Najvar, Laura K.
AU - Bocanegra, Rosie
AU - Kirkpatrick, William R.
AU - Graybill, John R.
AU - Patterson, Thomas F.
PY - 2012/6
Y1 - 2012/6
N2 - 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.
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.
KW - C. gattii
KW - Cryptococcal meningoencephalitis
KW - Cryptococcus neoformans
KW - Fluconazole
KW - Posaconazole
UR - http://www.scopus.com/inward/record.url?scp=84861108451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861108451&partnerID=8YFLogxK
U2 - 10.1093/jac/dks060
DO - 10.1093/jac/dks060
M3 - Article
C2 - 22378683
AN - SCOPUS:84861108451
VL - 67
SP - 1432
EP - 1438
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 6
M1 - dks060
ER -