Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/33471
Title: Efficacy of a poly-aggregated formulation of amphotericin B in treating systemic sporotrichosis caused by Sporothrix brasiliensis
Authors: Ishida, Kelly
Castro, Rafaela Alves
Torrado, Juan J.
Serrano, Dolores Remedios
Borba-Santos, Luana Pereira
Quintella, Leonardo Pereira
Souza, Wanderley de
Rozental, Sonia
Lopes-Bezerra, Leila M.
Affilliation: University of São Paulo. Institute of Biomedical Sciences. Department of Microbiology. Laboratory of Antifungal Chemotherapy. São Paulo, SP, Brazil.
Rio de Janeiro State University. Department of Cell Biology. Laboratory of Cellular Mycology and Proteomics. Rio de Janeiro, RJ, Brazil.
Complutense University. Faculty of Pharmacy. Department of Pharmacy and Pharmaceutical Technology. Madrid, Spain.
Complutense University. Faculty of Pharmacy. Department of Pharmacy and Pharmaceutical Technology. Madrid, Spain.
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Laboratory of Fungal Cell Biology. Rio de Janeiro, RJ, Brazil.
Rio de Janeiro State University. Faculty of Medical Sciences. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Biophysics Carlos Chagas Filho. Institute of Biophysics Carlos Chagas Filho. Rio de Janeiro, RJ, Brazil.
Rio de Janeiro State University. Department of Cell Biology. Laboratory of Cellular Mycology and Proteomics. Rio de Janeiro, RJ, Brazil.
Rio de Janeiro State University. Department of Cell Biology. Laboratory of Cellular Mycology and Proteomics. Rio de Janeiro, RJ, Brazil.
Abstract: In severe cases of sporotrichosis, it is recommended to use amphotericin B deoxycholate (D-AMB) or its lipid formulations and/or in association with itraconazole (ITC). Our aim was to evaluate the antifungal efficacy of a poly-aggregated amphotericin B (P-AMB), a nonlipid formulation, compared with D-AMB on systemic sporotrichosis caused by Sporothrix brasiliensis. In vitro assays showed that Sporothrix schenckii sensu stricto and S. brasiliensis yeast clinical isolates were susceptible to low concentrations of P-AMB and D-AMB. Although P-AMB presented a higher minimal inhibitory concentration (MIC) compared to D-AMB, its cytotoxic effect on renal cells and erythrocytes was lower. For the in vivo assays, male BALB/c mice were intravenously infected with S. brasiliensis yeasts, and P-AMB or D-AMB was administered 3 days post-infection. The efficacy of five therapeutic regimens was tested: intravenous monotherapy with P-AMB or D-AMB, intravenous pulsed-therapy with P-AMB or D-AMB, and intravenous therapy with P-AMB, followed by oral ITC. These treatments increased murine survival and controlled the fungal burden in the liver, spleen, lungs, and kidneys. However, only D-AMB monotherapy or the pulsed-therapies with D-AMB or P-AMB led to 100% survival of the mice 45 days post-infection; only pulsed administration of D-AMB was able to control the fungal load in all organs 45 days post-infection. Accordingly, the histopathological findings showed reductions in the fungal burden and inflammatory reactions in these treatment regimens. Together, our results suggest that the P-AMB formulation could be considered as an alternative drug to D-AMB for treating disseminated sporotrichosis.
Keywords: Sporotrichosis
Sporothrix brasiliensis
Poly-aggregated AMB
Amphotericin B
Sporotrichosis mouse model
Antifungal drugs
Issue Date: 2018
Publisher: Oxford University Press
Citation: ISHIDA, Kelly et al. Efficacy of a poly-aggregated formulation of amphotericin B in treating systemic sporotrichosis caused by Sporothrix brasiliensis. Medical Mycology, v. 56, p. 288-296, 2018.
DOI: 10.1093/mmy/myx040
ISSN: 1369-3786
Copyright: restricted access
Appears in Collections:INI - Artigos de Periódicos

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