title: Antifungal therapy in a murine model of disseminated infection by Cryptococcus gattii.
abstract: We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.
authors.affiliation: Unitat de Microbiologia, Facultat de Medicina, Universitat Rovira i Virgili. Carrer Sant Llorenç, 21.43201 Reus, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Pastor
authors.forename: M Mar
authors.initials: MM
authors.lastname: Rodríguez
authors.forename: Isabel
authors.initials: I
authors.lastname: Pujol
authors.forename: Josep
authors.initials: J
authors.lastname: Guarro
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D056285:Cryptococcus gattii / Q000187:drug effects* / Q000472:pathogenicity; D008297:Male; D051379:Mice; D011743:Pyrimidines / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B; D065819:Voriconazole