Chronic, non-healing wounds are serious and difficult-to-treat bacterial infections in children and patients with diabetes mellitus and peripheral vascular disease, with a treatment failure rate of 20-80% in the United States. Chronic wounds typically require an extended duration of treatment with a combination of antibiotics administered systemically and locally. They often require extensive surgical debridement, including amputation in patients. Our previous studies have shown that focused ultrasound- induced local warming decreases resistance in vascular beds to elevate local intravascular concentrations of systemically-administered drugs within the solid tumor, and mouse bacterial abscess. This method has not heretofore beenadapted to wound therapy in the clinical setting. This proposal builds upon the potential of focused ultrasound warming to reduce vascular resistance for non-invasive improvement of non-healing wound therapy in client-owned dogs. Unlike murine models, canine patients replicate the infection profile in humans, and thus a demonstration of focused ultrasound efficacy in our veterinary clinical trial would provide an easier path for human clinical trials. In the proposed one year project, we will optimize the focused ultrasound parameter that provides optimal enhancement of antimicrobial therapy. The therapy outcomes in the presence and absence of focused ultrasound exposures with enrofloxacin as a model drug agent will be determined (n=3-5 dogs/group). Treatment success will be evaluated histopathologically, and improvement in healing responses over 3 months post-treatment. If successful, this project can provide a novel mean to non-invasively enhance penetration and sensitivity to antimicrobial therapies by addition of mild hyperthermia, and minimize need of surgical intervention
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