Chronic MRSA infections remain challenging to treat in patients with cystic fibrosis (CF). The ability of the bacterial population to survive high concentrations of bactericidal antibiotics, including vancomycin, despite lacking resistance is considered one of the main reasons for treatment failures.

Bacterial biofilms are the leading cause of delayed healing in chronic wounds. Aminoglycoside antibiotics, such as gentamicin (Gent), are ineffective against biofilm cells as they maintain proton motive force below the threshold for drug uptake. We employ a novel aminoglycoside adjuvant, palmitoleic acid (PA), to facilitate drug uptake. Here, we propose a dual strategy to eradicate a chronic wound infection; utilizing ultrasound-stimulated nanodroplets (US+ND) to improve the penetration of the novel drug combination Gent/PA. A chronic wound infection model was established in SKH-1 hairless mice; 6–8 week old mice were treated with streptozocin to induce diabetes. A circular wound was created on the back of the mice and infected with methicillin-resistant Staphylococcus aureus (MRSA). Wounds were treated topically with Gent and/or PA, twice daily for four days. One daily antibiotic treatment was combined with US+ND. On day 5, mice were euthanized and the wound area was excised and plated to enumerate bacterial survivors. Neither Gent nor Gent/PA reduced bacterial burden but both treatments were significantly improved by applying US+ND to improve drug penetration. Importantly, bacteria were eradiated from 3 out of the 8 wounds in the Gent/PA group that were treated with US+ND. These data show that improving the penetration of a novel anti-biofilm drug combination is a viable strategy to eradicate biofilms in chronic wounds. [Some authors are inventors on patents related to this work.]