Phylogenetic and Structural Analysis of Miconazole Susceptibility in Malassezia pachydermatis Isolates From Dogs With Otitis Externa.

Miconazole-resistant M. pachydermatis exists in clinical practice; alternative azoles may be more effective.

This study investigated miconazole resistance in Malassezia pachydermatis isolates from dogs with otitis externa (OE) presenting to a tertiary veterinary practice. Researchers cultured yeast from ear swabs of 11 dogs (16 ears) with clinical and cytological evidence of yeast OE. Phylogenetic analysis using ITS, 18S/26S rRNA, and actin gene sequences revealed three distinct clades of M. pachydermatis. The ERG11 gene encoding lanosterol 14α-demethylase was sequenced and analyzed for mutations. Miconazole susceptibility was assessed via disk diffusion testing. Most ERG11 mutations were clade-specific without affecting susceptibility. However, amino acid substitutions at position A302 in the azole-binding site correlated with reduced miconazole susceptibility. Molecular modeling demonstrated that longer-tailed azoles make additional protein contacts beyond A302, potentially offering better efficacy against resistant strains. The study confirms that miconazole-resistant M. pachydermatis is present in routine clinical practice. The authors emphasize the need for antifungal stewardship to prevent development of pan-azole resistance, which would severely limit treatment options for canine malassezia-associated diseases.

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