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COMBINATION THERAPY OF ITRACONAZOLE AND AN ACYLHYDRAZONE DERIVATIVE (D13) FOR THE TREATMENT OF SPOROTRICHOSIS IN CATS
Gremião, Isabella Dib Ferreira et al. | Data do documento: 2024
Autor(es)
Gremião, Isabella Dib Ferreira
Pereira-Oliveira, Gabriela Reis
Pereira, Sandro Antonio
Corrêa, Maria Lopes
Borba-Santos, Luana Pereira
Viçosa, Alessandra Lifsitch
Garg, Ashna
Haranahalli, Krupanandan
Dasilva, Deveney
Sa, Nivea Pereira de
Matos, Gabriel S.
Silva, Vanessa
Lazzarini, Cristina
Fernandes, Caroline Mota
Miranda, Kildare
Bonilla, Jhon Jhamilton Artunduaga
Nunes, Anna Letícia
Nimrichter, Leonardo
Ojima, Iwao
Mallamo, John
McCarthy, John B.
Poeta, Maurizio Del
Afiliação
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Laboratory of Clinical Research on Dermatozoonoses in Domestic Animals. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Laboratory of Clinical Research on Dermatozoonoses in Domestic Animals. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Laboratory of Clinical Research on Dermatozoonoses in Domestic Animals. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Evandro Chagas National Institute of Infectious Diseases. Laboratory of Clinical Research on Dermatozoonoses in Domestic Animals. Rio de Janeiro, RJ, Brazil.
Carlos Chagas Filho Institute of Biophysics. Laboratory of Fungal Cell Biology. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Institute of Drug Technology - Farmanguinhos. Laboratory of Experimental Pharmacotechnics. Rio de Janeiro, RJ, Brazil.
Stony Brook University. Institute of Chemical Biology and Drug Discovery. Stony Brook, New York, USA.
Stony Brook University. Institute of Chemical Biology and Drug Discovery. Stony Brook, New York, USA / Stony Brook University. Department of Chemistry. Stony Brook, New York, USA.
Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA.
Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA.
Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA.
Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA.
Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA.
Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA.
Federal University of Rio de Janeiro. Carlos Chagas Filho Institute of Biophysics and National Center for Structural Biology and Bioimaging. Laboratory of Cellular Ultrastructure Hertha Meyer. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Paulo de Góes Institute of Microbiology. Laboratory of Eukaryotic Glycobiology. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Paulo de Góes Institute of Microbiology. Laboratory of Eukaryotic Glycobiology. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Paulo de Góes Institute of Microbiology. Laboratory of Eukaryotic Glycobiology. Rio de Janeiro, RJ, Brazil.
Stony Brook University. Institute of Chemical Biology and Drug Discovery. Stony Brook, New York, USA / Stony Brook University. Department of Chemistry. Stony Brook, New York, USA.
MicroRid Technologies Inc. Dix Hills, New York, USA.
MicroRid Technologies Inc. Dix Hills, New York, USA.
Stony Brook University. Institute of Chemical Biology and Drug Discovery. Stony Brook, New York, USA / Stony Brook University. Department of Microbiology and Immunology. Stony Brook, New York, USA / MicroRid Technologies Inc. Dix Hills, New York, USA / Stony Brook University. School of Medicine. Division of Infectious Diseases. Stony Brook, New York, USA / Veterans Administration Medical Center. Northport, New York, USA.
Resumo em Inglês
Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. Importance: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.
Palavras-chave em inglês
Cats
Sporothrix
Sporotrichosis
Itraconazole
Terbinafine
Acylhydrazone
Anti-fungal therapy
Fungal infection
 
Editor
American Society for Microbiology
Referência
GREMIÃO, Isabella Dib Ferreira et al. Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats. Microbiology Spectrum, v. 12, n. 6, p. 1-18, June 2024.
DOI
10.1128/spectrum.03967-23
ISSN
2165-0497