Ultrasound Cavitation From Low-Boiling Point Perfluorocarbon Phase Change Contrast Agents Correlates With Bacterial Burden Reduction in Antibiotic Treatment of Biofilm-Infected Murine Wounds.

OBJECTIVE: Chronic wounds are often infected by bacteria, which aggregate into biofilms. Biofilms impede antibiotic efficacy, promote infection relapse, and are the leading cause of chronic wound treatment failure. Ultrasound combined with phase-change contrast agents (PCCA) has shown potential to enhance antimicrobial delivery in animal models, yet quantification of cavitation in animal models remains unexplored. METHODS: In a murine wound infection model with methicillin-resistant Staphylococcus aureus (MRSA), animals received topical gentamicin and palmitoleic acid twice daily from days 2-4 post infection. One daily treatment was followed by administration of octafluoropropane (OFP) PCCA and ultrasound (1.1 MHz, 9.09% duty cycle) at either 700 or 1700 kPa. Passive cavitation signals were recorded every 15 seconds during five one-minute exposures. Cavitation dose was quantified from harmonic and broadband emissions and bacterial burden was assessed on day 5. RESULTS: A strong inverse correlation was observed between cavitation dose and wound bacterial burden (R2 = 0.88), indicating that increased cavitation was associated with greater reduction in bacterial burden. Cavitation was sustained throughout treatment with 1700 kPa and significantly higher than at 700 kPa (p = 0.0145), where signal declined over time. Limited wound coverage (∼40%) may have reduced overall efficacy. CONCLUSIONS: This study provides the first in vivo evidence correlating cavitation dose to bacterial reduction in MRSA biofilm-infected wounds. These findings support cavitation monitoring as a valuable feedback tool for optimizing ultrasound-enhanced antimicrobial therapies.