The addition of clotrimazole reduces but does not abrogate fungal dysbiosis during effective antibacterial therapy for canine otitis externa.

OBJECTIVES: Malassezia dysbiosis commonly occurs after successful piperacillin-tazobactam monotherapy for canine bacterial otitis externa. The study objective was to compare antimicrobial outcomes in dogs with otitis treated with piperacillin-tazobactam in combination with the antifungal drug clotrimazole with a previous cohort treated with piperacillin-tazobactam alone. MATERIALS AND METHODS: Twenty-one dogs with bacterial otitis were treated topically with piperacillin-tazobactam (1 mL) every 12 hours, although the fourth dose in each 48 hours period was replaced with 1% clotrimazole solution (1 mL). At visits 1 (V1) and 2 (V2), ear swab tips were washed in PBS + Triton X-100 and serial dilutions spread-plated onto blood, MacConkey (37°C, 48 hours) and modified Dixon's agar (32°C, 14 days) to generate semiquantitative counts. Microbes were identified by phenotype and MALDI-TOF. Outcomes were compared with those of 14 dogs previously treated with piperacillin-tazobactam alone (sequential case-cohort design). RESULTS: Relative risk of a post-treatment bacterial culture count exceeding zero in dogs treated with piperacillin-tazobactam-clotrimazole (3/21), when compared to piperacillin-tazobactam treatment alone (2/14) was 1.00 (95% confidence interval 0.19 to 5.24). Relative risk of an increase in yeast culture count in dogs treated with piperacillin-tazobactam alone (14/14), when compared to piperacillin-tazobactam-clotrimazole-treated dogs (7/21), was 3.00 (95% confidence interval 1.64 to 5.49). Relative risk of fungal dysbiosis (V2 yeast count > normal) in dogs treated with piperacillin-tazobactam alone (14/14), when compared to piperacillin-tazobactam-clotrimazole-treated dogs (4/21), was 5.25 (95% CI 2.17 to 12.68). CLINICAL SIGNIFICANCE: Piperacillin-tazobactam-clotrimazole is highly efficacious in the treatment of refractory bacterial otitis; incorporation of clotrimazole markedly reduces but does not abrogate fungal dysbiosis.