Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

Unitat de Microbiologia, Facultat de Medicina, Universitat Rovira i Virgili. Carrer Sant Llorenç, 21.43201 Reus, Spain.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 10/2010; 54(10):4074-7. DOI: 10.1128/AAC.00172-10
Source: PubMed


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.

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