High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis

Abstract Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. A...

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Autores principales:	Julliana Ribeiro Alves Santos, Noelly Queiroz Ribeiro, Rafael Wesley Bastos, Rodrigo Assunção Holanda, Letícia Chagas Silva, Estela Rezende Queiroz, Daniel Assis Santos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99c2bed22fe54969917ab9ebbd1e7e52
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spelling	oai:doaj.org-article:99c2bed22fe54969917ab9ebbd1e7e522021-12-02T11:53:12ZHigh-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis10.1038/s41598-017-04588-72045-2322https://doaj.org/article/99c2bed22fe54969917ab9ebbd1e7e522017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04588-7https://doaj.org/toc/2045-2322Abstract Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. Also, the antifungal 5FC is not available in many countries. Therefore, a combination of antifungal drugs may be an interesting option, but in vitro and theoretical data point to the possible antagonism between the main antifungals used to treat cryptococcosis, i.e., fluconazole (FLC), and amphotericin B (AMB). Therefore, in vivo studies are necessary to test the above hypothesis. In this study, the efficacy of FLC and AMB at controlling C. gattii infection was evaluated in a murine model of cryptococcosis caused by C. gattii. The infected mice were treated with FLC + AMB combinations and showed a significant improvement in survival as well as reduced morbidity, reduced lung fungal burden, and the absence of yeast in the brain when FLC was used at higher doses, according to the Tukey test and principal component analysis. Altogether, these results indicate that combinatorial optimization of antifungal therapy can be an option for effective control of cryptococcosis.Julliana Ribeiro Alves SantosNoelly Queiroz RibeiroRafael Wesley BastosRodrigo Assunção HolandaLetícia Chagas SilvaEstela Rezende QueirozDaniel Assis SantosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julliana Ribeiro Alves Santos Noelly Queiroz Ribeiro Rafael Wesley Bastos Rodrigo Assunção Holanda Letícia Chagas Silva Estela Rezende Queiroz Daniel Assis Santos High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis
description	Abstract Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. Also, the antifungal 5FC is not available in many countries. Therefore, a combination of antifungal drugs may be an interesting option, but in vitro and theoretical data point to the possible antagonism between the main antifungals used to treat cryptococcosis, i.e., fluconazole (FLC), and amphotericin B (AMB). Therefore, in vivo studies are necessary to test the above hypothesis. In this study, the efficacy of FLC and AMB at controlling C. gattii infection was evaluated in a murine model of cryptococcosis caused by C. gattii. The infected mice were treated with FLC + AMB combinations and showed a significant improvement in survival as well as reduced morbidity, reduced lung fungal burden, and the absence of yeast in the brain when FLC was used at higher doses, according to the Tukey test and principal component analysis. Altogether, these results indicate that combinatorial optimization of antifungal therapy can be an option for effective control of cryptococcosis.
format	article
author	Julliana Ribeiro Alves Santos Noelly Queiroz Ribeiro Rafael Wesley Bastos Rodrigo Assunção Holanda Letícia Chagas Silva Estela Rezende Queiroz Daniel Assis Santos
author_facet	Julliana Ribeiro Alves Santos Noelly Queiroz Ribeiro Rafael Wesley Bastos Rodrigo Assunção Holanda Letícia Chagas Silva Estela Rezende Queiroz Daniel Assis Santos
author_sort	Julliana Ribeiro Alves Santos
title	High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis
title_short	High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis
title_full	High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis
title_fullStr	High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis
title_full_unstemmed	High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis
title_sort	high-dose fluconazole in combination with amphotericin b is more efficient than monotherapy in murine model of cryptococcosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/99c2bed22fe54969917ab9ebbd1e7e52
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High-dose fluconazole in combination with amphotericin B is more efficient than monotherapy in murine model of cryptococcosis

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