Dalbavancin and wound healing: new evidences/insights in a mouse model of skin infection

ABSTRACT Dalbavancin is an effective antibiotic widely used to treat skin infection. Our aim was to determinate the effects of dalbavancin administration on wound healing compared to vancomycin, and to elucidate if EGFR, MMP-1, MMP-9 and VEGF could be involved in its therapeutic mechanism. A mouse model of MRSA skin infection was established. Mice were treated daily with vancomycin (10mg/kg) and weekly with dalbavancin, at day 1 (20 mg/kg) and day 8 (10 mg/kg). After 14 days wounds were excised and bacterial counts were perfomed. Wound healing was assessed by histological and immunohistochemical staining, followed by protein extraction and immunoblotting. Our microbiological results confirmed that both dalbanvancin and vancomycin are effective in reducing the bacterial load in wounds. Dalbavancin had a strong effect compared with infected untreated animals and vancomycin treated group. The wounds treated with dalbavancin showed robust epidermal coverage with a reconstitution of the regular and keratinized epidermal lining and a well-organized granulation tissue with numerous blood vessels, although slightly less than in the uninfected group, while in vancomycin treated group the epithelium appeared in general still hypertrophic, the granulation tissue appears even less organized. We observed elevated EGFR and VEGF expression in both treated groups, although it was higher in dalbavancin treated mice. MMP-1 and MMP-9 were decreased in uninfected and in both treated tissue when compared with untreatd infected wounds. This study showed faster healing with dalbavancin treatment that might be associated with a higher EGFR and VEGF levels.