Antifungal activity of azoles, allylamines, and 8-hidroxiquinolines, alone and in combination, against Malassezia pachydermatis in vitro and in vivo

Simone Merkel; Bruna Pippi; Paula Reginatto; Angélica R Joaquim; Gabriella R M Machado; Daiane Heidrich; Marina E Furasté; Jonnathan A Silva; Estela J S Konzen; Maria Lúcia Scroferneker; Saulo F Andrade; Alexandre M Fuentefria; Régis A Zanette

doi:10.1016/j.mycmed.2024.101475

Antifungal activity of azoles, allylamines, and 8-hidroxiquinolines, alone and in combination, against Malassezia pachydermatis in vitro and in vivo

J Mycol Med. 2024 Mar 11;34(2):101475. doi: 10.1016/j.mycmed.2024.101475. Online ahead of print.

Affiliations

¹ Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
² Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, UFRGS, Porto Alegre, Brazil.
³ Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Porto Alegre, Brazil.
⁴ Programa de Pós-Graduação em Medicina: Ciências Médicas, UFRGS, Porto Alegre, Brazil.
⁵ Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: regnitro@yahoo.com.br.

PMID: 38479291
DOI: 10.1016/j.mycmed.2024.101475

Abstract

Malassezia pachydermatis is often reported as the causative agent of dermatitis in dogs. This study aims to evaluate the in vitro and in vivo antifungal activity of azoles and terbinafine (TRB), alone and in combination with the 8-hydroxyquinoline derivatives (8-HQs) clioquinol (CQL), 8-hydroxyquinoline-5-(n-4-chlorophenyl)sulfonamide (PH151), and 8-hydroxyquinoline-5-(n-4-methoxyphenyl)sulfonamide (PH153), against 16 M. pachydermatis isolates. Susceptibility to the drugs was evaluated by in vitro broth microdilution and time-kill assays. The Toll-deficient Drosophila melanogaster fly model was used to assess the efficacy of drugs in vivo. In vitro tests showed that ketoconazole (KTZ) was the most active drug, followed by TRB and CQL. The combinations itraconazole (ITZ)+CQL and ITZ+PH151 resulted in the highest percentages of synergism and none of the combinations resulted in antagonism. TRB showed the highest survival rates after seven days of treatment of the flies, followed by CQL and ITZ, whereas the evaluation of fungal burden of dead flies showed a greater fungicidal effect of azoles when compared to the other drugs. Here we showed for the first time that CQL is effective against M. pachydermatis and potentially interesting for the treatment of malasseziosis.

Keywords: Antifungal drugs; Drosophila melanogaster; In vitro susceptibility; Malassezia pachydermatis; Systemic infection.