In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Efficacy of isavuconazole, voriconazole and fluconazole in temporarily neutropenic murine models of disseminated Candida tropicalis and Candida krusei.

Majithiya, J; Sharp, A; Parmar, A; Denning, D W; Warn, P A

The Journal of antimicrobial chemotherapy. 2009;63(1):161-6.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:

Full-text held externally


OBJECTIVES: The aim of this study was to assess the dose-response of isavuconazole, voriconazole and fluconazole in disseminated Candida tropicalis and Candida krusei infections. METHODS: Mice were immunosuppressed using either one dose [temporarily neutropenic (TN)] or two doses [persistently neutropenic (PN)] of cyclophosphamide. Treatment was started 5 h after infection with oral isavuconazole (6, 15, 30, 60, 90, 120 or 150 mg/kg equivalent active compound), intravenous voriconazole (5, 20 or 40 mg/kg plus grapefruit gavage twice daily) or oral fluconazole (15, 50 or 150 mg/kg) all administered twice daily. Kidney burden was assessed for C. tropicalis, and kidney and brain burden for C. krusei. RESULTS: Vehicle controls developed a non-lethal infection with high burdens in both models. In the TN models, isavuconazole, voriconazole and fluconazole (>50 mg/kg) reduced kidney burden compared with controls; >60 mg/kg isavuconazole and 50 mg/kg fluconazole were superior to alternative treatments (other than voriconazole 40 mg/kg). Isavuconazole (all doses) reduced brain burden (P<0.05) in the C. krusei model; fluconazole (all doses) and voriconazole (5 and 20 mg/kg) did not. In the C. krusei kidney burden model, isavuconazole 120 and 150 mg/kg and voriconazole 40 mg/kg were superior to controls and fluconazole. In the C. tropicalis model, PN isavuconazole (all doses), voriconazole (>5 mg/kg) and fluconazole (all doses) reduced kidney burden (P<0.05). Only isavuconazole (all doses) and 40 mg/kg voriconazole were effective against C. krusei in the brain, isavuconazole and voriconazole reduced tissue burden (P<0.05). Fluconazole had no significant effect on brain burden even at 150 mg/kg. CONCLUSIONS: Isavuconazole significantly reduced kidney burden in mice infected with C. tropicalis and both kidney and brain burdens in mice infected with C. krusei. Isavuconazole was as effective as voriconazole and much more effective than fluconazole at reducing brain burden.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Published date:
Abbreviated journal title:
Place of publication:
Digital Object Identifier:
Pubmed Identifier:
Pii Identifier:
Access state:

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
Created by:
Warn, Peter
5th September, 2011, 12:57:14
Last modified by:
Warn, Peter
Last modified:
28th October, 2015, 13:28:29

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.