New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection.

Abstract

Dalbavancin is an effective antibiotic that is widely used to treat skin infection. Our aim was to determine the effect of dalbavancin administration on wound healing compared to that of vancomycin and to elucidate if epidermal growth factor receptor (EGFR), matrix metalloproteinase 1 (MMP-1), MMP-9, and vascular endothelial growth factor (VEGF) could be involved in its therapeutic mechanism. A mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection was established. Mice were treated daily with vancomycin (10 mg/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 performed. Wound healing was assessed by histological and immunohistochemical staining, followed by protein extraction and immunoblotting. Our microbiological results confirmed that both dalbavancin and vancomycin are effective in reducing the bacterial load in wounds. The dalbavancin group showed a strong effect compared with infected untreated animals and the vancomycin-treated group. The wounds treated with dalbavancin showed robust epidermal coverage with reconstitution of the regular and keratinized epidermal lining and well-organized granulation tissue with numerous blood vessels, although slightly less than that in the uninfected group. While in the vancomycin-treated group the epithelium appeared, in general, still hypertrophic, the granulation tissue appeared 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 tissue and in both treated tissues compared with untreated infected wounds. This study showed faster healing with dalbavancin treatment that might be associated with higher EGFR and VEGF levels.

• Authors: Oriana Simonetti, Guendalina Lucarini, Gianluca Morroni, Fiorenza Orlando, Raffaella Lazzarini, Antonio Zizzi, Lucia Brescini, Mauro Provinciali, Andrea Giacometti, Annamaria Offidani, Oscar Cirioni
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 64 Issue 4 (03 24 2020) ISSN: 1098-6596 [Electronic] United States
• PMID: 31932371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 American Society for Microbiology.

Chemical References

• Anti-Bacterial Agents
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Teicoplanin
• Vancomycin
• dalbavancin
• EGFR protein, mouse
• ErbB Receptors
• Matrix Metalloproteinase 13
• Mmp13 protein, mouse
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Bacterial Load (drug effects)
• Disease Models, Animal
• ErbB Receptors (metabolism)
• Matrix Metalloproteinase 13 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred BALB C
• Staphylococcal Skin Infections (drug therapy)
• Staphylococcus aureus (drug effects)
• Surgical Wound Infection (drug therapy)
• Teicoplanin (analogs & derivatives, therapeutic use)
• Vancomycin (pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)
• Wound Healing (drug effects)