Inter-laboratory comparison of treatment response in a murine model of invasive candidiasis using two Candida albicans isolates

N.P. Wiederhold*, P.A. Warn, L.K. Najvar, J. Livermore, R. Bocanegra, W.R. Kirkpatrick, T.F. Patterson

Author address: 

(San Antonio, US; Manchester, UK)

Abstract: 

Objective: Murine models of invasive candidiasis are frequently used in the preclinical evaluation of investigational antifungals as these models are typically robust and inexpensive. However, there have been few inter-laboratory studies of outcome variability with the same model. Our objective was to conduct an inter-laboratory comparison of treatment response between two laboratories (UTHSCSA and University of Manchester) using a murine model of invasive candidiasis with two different C. albicans clinical isolates. Methods: Immunocompetent 30 g outbred ICR or CD1 mice were inoculated intravenously with C. albicans SC5314 or ATCC 90028 (target starting inocula 1.5 · 105 and 1.5 · 106 cells/mouse, respectively). Antifungal therapy began 1 day later and continued for 5 days. Treatment groups consisted of control, fluconazole (FLC) 10 mg/kg PO QD, and caspofungin (CFG) 1 mg/kg IP QD. Treatment continued until day 5 and mice were followed off therapy until day 21 to assess survival. Kidneys and brains were collected on day 8 in the fungal burden arm. Fungal burden was assessed by colony-forming units (CFU), and survival was assessed by Kaplan-Meier analysis. Each laboratory evaluated both isolates and conducted the experiments independently. Results: Antifungal response, as measured by reductions in kidney fungal burden and improvements in survival, was very similar between the two laboratories (Table). CFG significantly improved survival and
2012

abstract No: 

NULL

Full conference title: 

22nd European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 22nd (2012)