Therapeutic efficacy and dermal safety of topical clove essential oil spray against bacterial, yeast, and fungal skin infections in rat models: A pilot non-inferiority study

Background and Aim: Infectious dermatitis caused by bacterial, yeast, and fungal pathogens is an important veterinary concern, while antimicrobial resistance and adverse effects associated with conventional therapies highlight the need for safe topical alternatives. Clove essential oil exhibits broad antimicrobial activity; however, controlled evidence of its therapeutic efficacy against multiple cutaneous pathogens remains limited. This pilot study evaluated the non-inferiority and dermal safety of a topical clove essential oil spray compared with standard treatments in rat models of pyoderma, Malassezia dermatitis, and dermatophytosis. Materials and Methods: Thirty Wistar Hannover rats were allocated among experimental skin infection models induced with Staphylococcus pseudintermedius, Malassezia pachydermatis, or Microsporum canis. For each model, four rats received 2.5% w/w clove essential oil spray, four received the standard treatment (2% w/v chlorhexidine for S. pseudintermedius or 2% w/v ketoconazole for M. pachydermatis and M. canis), and two served as negative controls. Treatments were applied topically twice daily for 15 days. Therapeutic efficacy was assessed on days 5, 10, and 15 using percentage reduction in clinical index score (CIS), pathogen reduction, and culture negativity. Non-inferiority was evaluated using a prespecified margin of −20% for CIS reduction. Dermal irritation was assessed using erythema and edema scores.