1683. Antifungal Activity of Alexidine Dihydrochloride in a Novel Diabetic Mouse Model of Dermatophytosis

Abstract

Abstract Background Ringworm caused by the dermatophyte species Trichophyton is the foremost superficial fungal infection worldwide. The US alone records over 5 million outpatient visits due to dermatophytosis, with an annual burden of one billion dollars in associated direct medical costs. Patients with diabetes mellitus exhibit a higher incidence rate and a more severe manifestation of the disease. Infections are often recurrent and recalcitrant to most antifungal drugs and new molecules to combat these discomforting infections are sorely needed. Here, we establish a novel model of dermatophytosis, which is clinically relevant, simple to use, and is robust enough for evaluation of antifungal drugs. Using this model, we demonstrate that an FDA-approved small molecule alexidine dihydrochloride has enhanced efficacy against dermatophytes. Methods For the animal model, ICR mice (equal gender) were rendered diabetic by treatment with a single intraperitoneal dose of streptozotocin, followed by confirmation of glycosuria and ketonuria. The back of the anesthetized diabetic mice was shaved, skin abraded with sand paper, and inoculated with 50 µl of sterile water containing 5x10^7 conidia. Infected lesions were monitored daily, and graded for erythema, edema, and extent of infection over a period of 2 weeks. For drug treatment, infected mice were separated equally into four groups: topical treatment of 20 µg/ml alexidine dihydrochloride, topical 1% terbinafine, 10 mg/kg terbinafine by oral gavage, and a vehicle control. Treatment was started on day 4 post infection and given once daily for 7 days. Lesions were monitored as above and clearance of infection was confirmed by fungal culture and histopathology. Results In the absence of drugs, dry, scaly erythematous legions appeared on day 3 after infection and became progressively worse, persisting for at least 14 days. Terbinafine and Alexidine dihydrochloride were highly efficacious in curbing infections within two days after treatment and no recurrence was observed for up to 10 days post treatment. Conclusion The diabetic mouse model was found to be reproducible and applicable for primary evaluation of the anti-dermatophytic efficacy of topical and oral formulations of antifungal agents. Disclosures All Authors: No reported disclosures.