Efficacy of voriconazole in a murine model of invasive paecilomycosis.
We studied the efficacy of voriconazole (VRC) and amphotericin B (AMB) in an immunosuppressed murine model of disseminated infection by two strains of Paecilomyces lilacinus. Mice were treated with VRC 60 mg/kg/day orally or AMB 3mg/kg/day intraperitoneally, beginning 1 day after infection and continuing for 9 days. To avoid rapid clearance of VRC, animals receiving VRC and the control group were given grapefruit juice instead of water. VRC significantly prolonged survival with respect to the group treated with AMB and the control group for both strains (P=0.005 and P<0.0001, respectively, for strain FMR 5522; and P=0.0002 and P<0.0001, respectively, for strain FMR 8252). VRC reduced the fungal load in the spleen, kidneys and liver of infected mice for both strains tested. Survival of mice challenged with strain FMR 8252 treated with AMB did not differ from that of the control group (P=0.223), being worse than that of the mice treated with VRC (P=0.0002). AMB was not able to reduce the tissue burden in any organ with respect to the control group for both strains studied.
Unitat de Microbiologia, IISPV, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Carrer Sant Llorenç, 21.43201 Reus, Spain.
M Mar
MM
Rodríguez
F Javier
FJ
Pastor
Carolina
C
Serena
Josep
J
Guarro
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D032083:Citrus paradisi; D015169:Colony Count, Microbial; D004032:Diet / Q000379:methods; D016867:Immunocompromised Host; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D008297:Male; D051379:Mice; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D010143:Paecilomyces / Q000187:drug effects*; D011743:Pyrimidines / Q000627:therapeutic use*; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D065819:Voriconazole