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Correspondence of In Vitro and In Vivo Fluconazole Dose-Response Curves for Cryptococcus neoformans

Authors
  • Robert A. Larsen
  • Madeline Bauer
  • Ann M. Thomas
  • Alejandro Sanchez
  • Diane Citron
  • Meri Rathbun
  • Thomas S. Harrison
Publisher
American Society for Microbiology
Publication Date
Aug 01, 2005
Source
PMC
Keywords
Disciplines
  • Biology
License
Unknown

Abstract

We conducted in vitro experiments to evaluate the susceptibility of a clinical isolate of Cryptococcus neoformans to a wide range of concentrations of fluconazole. In vitro susceptibility was tested using broth macrodilution methods modified to provide a numeric count of viable organisms. The association between the quantitative in vitro response and fluconazole drug concentrations was estimated using local nonparametric regression. Regression analysis was used to assess the correspondence between the in vitro fluconazole concentration-response curve and the murine dose-response curve observed in our previously reported murine model. The regression model was then used to predict the murine response. There was a strong correspondence between in vitro measures of response to fluconazole alone and the previously reported biologic effects seen in the mouse. In vitro antifungal drug susceptibility testing can reliably predict the murine response to fluconazole.

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