Comparative Efficacy of Antibiotic Alternatives in Canine Otitis Externa

Thesis Abstract

Canine otitis externa (COE) remains a prevalent inflammatory ear condition with increasing concerns over antimicrobial resistance, treatment costs, and owner compliance. This study addresses the comparative efficacy of antibiotic alternatives to conventional antibiotics in COE, with the aim of identifying effective, non-antibiotic or antibiotic-sparing interventions that reduce relapse rates and support antimicrobial stewardship. Specific objectives are (1) to evaluate the clinical efficacy of selected antibiotic alternatives, including antiseptics (chlorhexidine-based formulations), essential oil–based preparations, non-steroidal anti-inflammatory components, and immunomodulatory agents, against standard systemic and topical antibiotics; (2) to compare relapse rates, microbiological cure, and otoscopic healing across treatment arms over a 12-week follow-up; (3) to assess tolerability, owner compliance, and cost-effectiveness; and (4) to explore potential moderators such as etiology (bacterial vs. yeast-dominant OTitis) and severity grade on treatment outcomes. A multicenter, randomized, controlled trial design will be employed. The study will enroll 240 client-owned dogs diagnosed with unilateral or bilateral COE across five veterinary teaching hospitals. Animals will be stratified by severity (mild, moderate, severe) and etiologic predominance (bacterial, Malassezia-dominant) and then randomly assigned to one of four arms (a) standard topical antibiotic (ayllacin-based combination) plus placebo, (b) chlorhexidine antiseptic formulation, (c) plant-derived essential oil–based preparation, and (d) a non-antibiotic immunomodulatory agent (e.g., a topical cytokine modulator). A fifth arm incorporating a standard antibiotic with an antiseptic adjuvant will serve as a pragmatic comparator. Data collection will include baseline and follow-up otoscopic scores, cytology, culture and sensitivity, owner-reported symptom diaries, and quality-of-life indices. Microbiological sampling will identify bacterial and yeast counts and resistance patterns using MALDI-TOF and disk diffusion assays. The primary outcome is clinical cure at 8 weeks, defined as complete resolution of cerumen, erythema, and edema, with no relapse at 12 weeks. Secondary outcomes include microbiological cure, time-to-improvement, recurrence rate, adverse events, and cost per successfully treated case. Data analysis will utilize intention-to-treat principles. Descriptive statistics will summarize demographics and baseline characteristics. Primary outcome analysis will employ Cox proportional hazards models to compare time-to-cure across groups, adjusted for severity and etiologic category. Logistic regression will assess odds of clinical cure at 8 weeks, while repeated-measures ANOVA or linear mixed-effects models will analyze longitudinal otoscopic and owner-reported outcomes. Subgroup analyses will examine interaction effects between etiology and treatment arm. Microbiological data will be analyzed with chi-square tests for proportions and ANOVA for colony counts, with post hoc pairwise comparisons adjusted by Benjamini-Hochberg to control false discovery rate. Economic evaluation will perform cost-effectiveness analysis from the veterinary practice and owner perspectives, calculating incremental cost-effectiveness ratios per additional cured case. Theoretical framing will draw on the One Health approach and the Theory of Planned Behavior to interpret adherence and practice implications. Expected findings anticipate that antiseptic and immunomodulatory alternatives will demonstrate non-inferiority to standard topical antibiotics in clinical and microbiological outcomes for Malassezia-dominant COE, with superior reductions in relapse rates in mixed or bacterial-dominant cases when used as adjuvants. Plant-derived preparations are expected to show acceptable tolerability, with variable efficacy depending on the etiology, while antibiotic-sparing regimens may reduce selection pressure for resistant organisms without compromising clinical outcomes in selected subgroups. The study will contribute to knowledge by providing robust comparative evidence on non-antibiotic strategies in COE, informing evidence-based guideline development, and supporting antimicrobial stewardship in veterinary medicine. It will also offer practical data on owner acceptability and cost implications, aiding clinicians in shared decision-making. The main conclusion is that targeted, pathogen-specific use of antibiotic alternatives can achieve comparable clinical resolution and acceptable microbiological outcomes in COE while reducing antibiotic exposure; recommendations will emphasize phenotype-guided therapy, integration of antiseptics and immunomodulators into standard care for selected patients, and ongoing surveillance of resistance patterns. Further research should explore long-term outcomes beyond 12 weeks and evaluate combinations of antiseptics with immunomodulators in diverse canine populations.