Growing miconazole resistance: There’s a reason that yeast ear infection is so stubborn

If a dog keeps bouncing back to your clinic with a yeasty ear that just won't clear up on miconazole, the organism may be one step ahead of you.

A new study published this month in Veterinary Dermatology found miconazole-resistant Malassezia pachydermatis in routine canine otitis externa cases—mostly traced to a small tweak in a single gene.¹

Clarissa Pimentel de Souza, DVM, DACVD, an assistant professor of veterinary clinical medicine at the University of Illinois College of Veterinary Medicine, had been seeing more recurrent cases of fungal otitis that weren't responding to standard topical treatment. She brought it up in conversation with Lois Hoyer, PhD, a professor of pathobiology at the University of Illinois, and the 2 of them designed a study to find out what was going on.²

As Souza describes it, the resistance problem often starts with a clinical shortcut that makes intuitive sense in the moment but accumulates over time.²

“A common situation seen in practice is the use of an antifungal to treat recurrent yeast otitis externa without addressing the underlying allergies driving the infection,” Souza said. “If the primary allergic disease is not concurrently worked up, the dog will develop another infection shortly after the discontinuation of the topical antifungal.

“This situation leads to the chronic use of antifungals in the ears, which can be a risk factor for developing resistance,” she added. ²

The researchers cultured yeast from 16 affected ears across 11 client-owned dogs, all with otoscopic and cytologic confirmation of Malassezia infection.¹ Samples went to a veterinary microbiologist, who grew pure cultures. Hoyer’s team then sequenced the isolates across 4 genetic regions to see how the strains related to one another.

From there, the team zeroed in on the ERG11 gene, which encodes a protein yeast needs to build its cell membrane and is the direct target of azole antifungals.¹

What they found

Most of those genetic changes turned out to be clade markers, but one specific change tracked tightly with miconazole resistance. A substitution at a spot called A302 sits inside the pocket where the drug needs to dock, and even a small change there can be enough to block the interaction.¹

“The most common topical antifungal treatments prescribed are azoles, and miconazole is the first line of defense,” Souza said in the news release.² “If the resistance is caused by a gene mutation altering the structure of the target protein, the antifungal cannot bind to it and will not kill the yeast.”

According to the researchers, miconazole is a small molecule with only a handful of contact points in its target pocket. When A302 gets crowded, the drug loses its grip. Longer-tailed azoles such as posaconazole are larger and make many more contacts across the binding site, so a single disrupted contact doesn't break the whole interaction. The team's modeling found that isolates resistant to miconazole were effectively treated with posaconazole.¹

Resistance with a clinical backstory

Every dog whose isolate showed reduced miconazole susceptibility had a documented history of azole treatment—miconazole wipes, ketoconazole-containing ear flushes, oral ketoconazole, posaconazole otic products, and combinations of the above.¹ The yeast, in other words, was being selected for resistance by the very products meant to treat it.

What it means for practice

Some veterinarians might be tempted to jump straight to posaconazole to treat a stubborn yeast ear infection, but Souza said that’s not the best approach.²

“Based on our findings, it is recommended to use a topical short-tailed azole, such as miconazole or clotrimazole, as an initial therapy for dogs with yeast ear infections,” Souza said in the news release. “The medium- and longer-tailed azoles, such as ketoconazole and posaconazole, respectively, should be reserved for recurrent or nonresponsive cases.”

The authors also flagged the piece of this that many veterinarians already know, but that can be hard to execute in a busy practice: Treating the yeast without treating the underlying allergic disease is a recipe for the exact cycle the study documents.

The research team plans to next test the resistant isolates against a broader panel of azoles and to collect more samples from likely-resistant cases to build out the picture. “We want to learn how best to steward the antimicrobial agents we have,” Hoyer said.²

References

1. Belcher CM, Souza CP, McGuire E, Hung CC, Tyndall JDA, Hoyer LL. Phylogenetic and structural analysis of miconazole susceptibility in Malassezia pachydermatis isolates from dogs with otitis externa. Vet Dermatol. Published online March 19, 2026. doi:10.1111/vde.70059

2. Unlocking how dogs' fungal ear infections evade treatment points vets to drug stewardship. News release. University of Illinois at Urbana-Champaign. April 7, 2026. Accessed April 21, 2026. https://www.eurekalert.org/news-releases/1123181