EFFICACY OF VORICONAZOLE IN TREATMENT OF SYSTEMIC SCEDOSPORIOSIS IN IMMUNOSUPPRESSED MICE

Capilla J, Serena C, Ortoneda M, Pastor FJ, Guarro J

Author address: 

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Abstract: 

Scedosporium apiospermum is an opportunistic filamentous fungus which causes severe human infections in immunodepressed but also in immunocompetent people. Patients are usually treated with amphotericin B (AMB) alone or combined with other drugs commonly with unsuccessful outcomes. Voriconazole (VCZ) is one of the few drugs that has demonstrated in vitro activity against this fungus. We have evaluated the efficacy of VCZ in prolongation of survival (i) and reduction of tissue burden (ii) in a murine model of systemic scedosporiosis. i) Immunosuppressed animals were infected via lateral tail vein with a conidial suspension of 5x10 4 CFU/animal. Three days prior to the infection, drinking water was changed for grapefruit juice. The following 6 treatment groups were established: control, AMB treated (0.8 mg/kg/day i.v. or 1 mg/kg/day i.p.) and VCZ treated (3 doses: 5, 20 and 40 mg/kg/day p.o.). Treatments were administered once daily for 10 days post infection. ii) Mice were infected also i.v with inocula of 3.4x10 3 CFU/animal. Three groups were established: Control, AMB treated (0.8 mg/Kg/day i.v.) and VCZ treated (40 mg/Kg/day p.o.). Treatments were also administered for 10 days and 24 h after the last dose, surviving animals were sacrificed. Brain, kidney, liver and spleen were removed aseptically, weighted and homogenized in saline 0.9% and serial dilutions of these homogenates were placed on PDA plates. The most affected organs in untreated animals were brain (5.58 log10 CFU/g ± 0.25) and kidneys (4.58 log10 CFU/g ± 0.14). The three doses of VCZ increased significantly survival in comparison to the control group (p = 0.007, 0.043 and 0.0002, respectively) and to the AMB treated group (p > 0.05 in all cases). AMB was ineffective in reducing the number of CFU/g in all the studied organs. However, animals treated with VCZ reduced significantly tissue burden in liver and brain in comparison to the control ( p
2003

abstract No: 

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Full conference title: 

The 15 th Congress of the International Society for Human and Animal Mycology
    • ISHAM 15th (2003)