Efficacy of Isavuconazole, Voriconazole and Fluconazole in a Neutropenic Murine Model of Candida krusei.

J. MAJITHIYA, A. SHARP, A. PARMAR, D. DENNING, P. WARN;

Author address: 

The Univ. of Manchester, Manchester, United Kingdom.

Abstract: 

Background: Isavuconazole (ISA) is the water-soluble prodrug of the triazole BAL4815 with broad-spectrum antifungal activity. Understanding the effect of drug exposure during infection is essential in the optimization of antifungal therapeutic regimes. We examined the dose response of ISA, voriconazole (VCZ) and fluconazole (FLU) on the tissue burden of neutropenic mice with disseminated Candida krusei. Methods: Male CD1 were immunosuppressed using either 1 dose (TN) or two doses (PN) of 200mg/kg cyclophosphamide. Groups of 6 mice were infected IV with 1 x 107cfu/mouse C. krusei and treated 5 hours later with solvent, oral ISA (30, 60, 90, 120, 150 mg/kg equivalent active compound), IV VCZ (5, 20, 40 mg/kg plus grapefruit gavage BD) or oral FLU (15, 50, 150 mg/kg) twice daily. 96 hours post infection mice were killed, brain and kidney were removed for quantitative culture. Results: Solvent controls developed a non-lethal infection with high burdens in both models, 4.1 x 105 (TN) 3.8 x 106 (PN) and 1.7 x 106 (TN) 4.9 x 106 (PN) log10cfu/g tissue in kidneys and brain respectively. TN Model: ISA, VCZ and FLU dose dependently reduced kidney burden as compared to control (P90mg/kg and VRC 40mg/kg superior. In the brain ISA and VCZ (all doses) reduced tissue burden (p
2007

abstract No: 

M-1838

Full conference title: 

47th Interscience Conference on Antimicrobial agents and Chemotherapy
    • ICAAC 47th