title: Correspondence of in vitro and in vivo fluconazole dose-response curves for Cryptococcus neoformans.
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.
authors.affiliation: Department of Medicine (Infectious Diseases), 2020 Zonal Ave., IRD Room 620, MC 9520, University of Southern California, Los Angeles, CA 90033, USA. rlarsen@usc.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Larsen
authors.forename: Madeline
authors.initials: M
authors.lastname: Bauer
authors.forename: Ann M
authors.initials: AM
authors.lastname: Thomas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez
authors.forename: Diane
authors.initials: D
authors.lastname: Citron
authors.forename: Meri
authors.initials: M
authors.lastname: Rathbun
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015725:Fluconazole / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D012044:Regression Analysis
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole