High Intensity Focused Ultrasound (HIFU) Heating Improves Perfusion and Antimicrobial Efficacy in Mouse Staphylococcus Abscess

Abstract

Chronic wounds typically require long-duration treatment with a combination of antibiotics administered systemically. This incurs adverse side effects and can require aversive surgical treatments and limb amputations. To improve non-invasive antimicrobial therapy, the objective of this study was to investigate antimicrobial chemotherapy combined with high-intensity focused ultrasound (HIFU) heating (HT). A Staphylococcus aureus abscess (80 ± 30 mm3) was generated in the mouse flank region. Once the average temperature (~42 °C–46 °C) in the abscess was reached with HIFU-HT, a broad-spectrum antimicrobial (ciprofloxacin, 10 mg/kg) and perfusion marker (Evans blue dye, 40 mg/kg wt) were administered intravenously via the tail vein. Four hours later, mean abscess perfusion and colony-forming units (CFUs) per gram of abscess were determined. HIFU-HT increased abscess perfusion by ~2.5-fold (4 ± 0.6 µg/mL Evans blue) compared with control (1.5 ± 0.7 µg/mL), and improved antimicrobial efficacy to decrease percentage average survival of S. aureus by ~20% (46 ± 7 CFUs/g of abscess) versus that seen with ciprofloxacin alone (61 ± 4 CFU/g). Our in vivo data suggest that HIFU-HT can improve antimicrobial treatment responses against deep-seated bacteria in abscess wounds via enhanced perfusion.