Antifungal therapy in a murine model of disseminated infection by Cryptococcus gattii.

Antimicrobial Agents and Chemotherapy
Enrique CalvoJosep Guarro

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.

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Citations

Feb 15, 2012·Antimicrobial Agents and Chemotherapy·Fabiola Fernández-SilvaJosep Guarro
Sep 7, 2016·Medical Mycology Case Reports·Stefanie DesmetBert Bammens
Jun 27, 2018·Expert Opinion on Drug Metabolism & Toxicology·Katharine E Stott, William Hope
Jan 8, 2014·Clinical Microbiology Reviews·Timothy FeltonWilliam W Hope
Dec 14, 2019·Archives of Microbiology·Cristina de Castro SpadariKelly Ishida
Dec 1, 2010·Eukaryotic Cell·Yaoping Liu, Scott G Filler
Oct 17, 2019·Journal of Fungi·Elizabeth Dodds Ashley
Oct 11, 2017·Medical Mycology·Marliete Carvalho CostaDaniel Assis Santos
Apr 24, 2020·Drugs·Lu ChenRoger J M Brüggemann

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