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
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Publicado: Nature Portfolio 2017
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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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