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Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats

  • Isabella Dib Ferreira Gremião
  • , Gabriela Reis Pereira-Oliveira
  • , Sandro Antonio Pereira
  • , Maria Lopes Corrêa
  • , Luana Pereira Borba-Santos
  • , Alessandra Lifsitch Viçosa
  • , Ashna Garg
  • , Krupanandan Haranahalli
  • , Deveney Dasilva
  • , Nivea Pereira de Sa
  • , Gabriel S. Matos
  • , Vanessa Silva
  • , Cristina Lazzarini
  • , Caroline Mota Fernandes
  • , Kildare Miranda
  • , Jhon Jhamilton Artunduaga Bonilla
  • , Anna Letícia Nunes
  • , Leonardo Nimrichter
  • , Iwao Ojima
  • , John Mallamo
  • John B. McCarthy, Maurizio Del Poeta
  • Fundação Oswaldo Cruz
  • Universidade Federal do Rio de Janeiro
  • Stony Brook University
  • MicroRid Technologies Inc.

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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 efficacyof the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilmsformed by Sporothrix brasiliensis. In a clinical study, the effectof 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 fivecases 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 effectivenessand the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.

Original languageEnglish
JournalMicrobiology Spectrum
Volume12
Issue number6
DOIs
StatePublished - Jun 2024

Keywords

  • Sporothrix
  • anti-fungal therapy
  • cats
  • fungal infection
  • itraconazole
  • sporotrichosis
  • terbinafine,acylhydrazone

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