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.