Comparative efficacy of selenoureido carbonic anhydrase inhibitors and azole antifungal drugs against clinical isolates of Malassezia pachydermatis.

Abstract

Background: Malassezia pachydermatis (MP) is implicated in severe dermatitis and otitis externa (OE) of companion animals and recently gained attention for its increasing resistance to azole compounds. For this reason, developing novel therapeutic strategies is of great interest. In a previous work, we used reference yeast isolates to evaluate several compounds bearing acyl/selenoureido moieties and primary/secondary sulfonamide groups for antifungal activity through organic selenium and carbonic anhydrase inhibition.

Objectives: This work aimed to evaluate the antifungal efficacy of eight selenoureido compounds on 36 clinical MP isolates from dogs, compared to selected azoles, notably ketoconazole (KCZ), miconazole (MCZ) and fluconazole (FCZ).

Materials and methods: MIC assays of 5g, 7a, 7c, 7k, 8c, 10c, 11b, 11f, KCZ, MCZ and FCZ were performed on 36 MP field isolates isolated from dogs affected by dermatitis and/or OE in which yeast aetiology was suspected. Minimum 50% and 90% inhibitory concentrations (MIC₅₀ and MIC₉₀) were calculated. MP identification was confirmed with a nested PCR for the internal transcribed spacer region of the rRNA gene.

Results: Overall, the MIC₅₀ of the tested compounds on MP field isolates was higher than the MICs obtained on reference MP DSM 6172. Although KCZ showed the lowest MIC₅₀ value, compounds 5g, 7a and 7k showed lower MIC₅₀s than MCZ and FCZ. Five clinical isolates showed a MIC on azoles >MIC₉₀. Compounds 7a (four of five), 10c (three of five) and 8c (three of five) showed lower MIC values on these isolates compared to the tested azoles, suggesting good activity in phenotypically azole-resistant MP.

Conclusions and clinical relevance: Considering the increasing azole resistance of the Malassezia genus, selenoureido compounds could represent a potential topical treatment for dog skin and ear mycotic infections.