Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant Staphylococcus aureus Infection Model

Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00606-17. doi: 10.1128/AAC.00606-17. Print 2017 Sep.

Abstract

Prolonged hospitalization and antibiotic therapy are risk factors for the development of methicillin-resistant Staphylococcus aureus (MRSA) infections in thermal burn patients. We used a rat model to study the in vivo efficacy of daptomycin in the treatment of burn wound infections by S. aureus, and we evaluated the wound healing process through morphological and immunohistochemical analysis. A copper bar heated in boiling water was applied on a paraspinal site of each rat, resulting in two full-thickness burns. A small gauze was placed over each burn and inoculated with 5 × 107 CFU of S. aureus ATCC 43300. The study included two uninfected control groups with and without daptomycin treatment, an infected control group that did not receive any treatment, and two infected groups treated, respectively, with intraperitoneal daptomycin and teicoplanin. The main outcome measures were quantitative culture, histological evaluation of tissue repair, and immunohistochemical expression of wound healing markers: epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF-2). The highest inhibition of infection was achieved in the group that received daptomycin, which reduced the bacterial load from 107 CFU/ml to about 103 CFU/g (P < 0.01). The groups treated with daptomycin showed better overall healing with epithelialization and significantly higher collagen scores than the other groups, and these findings were also confirmed by immunohistochemical data. In conclusion, our results support the hypothesis that daptomycin is an important modulator of wound repair by possibly reducing hypertrophic burn scar formation.

Keywords: MRSA; burns; daptomycin; teicoplanin; wound healing.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Load / drug effects
  • Burns / drug therapy*
  • Burns / microbiology
  • Cell Proliferation
  • Cicatrix / drug therapy
  • Daptomycin / therapeutic use*
  • Disease Models, Animal
  • Epithelial Cells / cytology
  • ErbB Receptors / biosynthesis
  • Fibroblast Growth Factor 2 / biosynthesis
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control*
  • Teicoplanin / therapeutic use*
  • Wound Healing / drug effects*
  • Wound Healing / physiology
  • Wound Infection / drug therapy
  • Wound Infection / microbiology
  • Wound Infection / prevention & control*

Substances

  • Anti-Bacterial Agents
  • Fibroblast Growth Factor 2
  • Teicoplanin
  • Egfr protein, rat
  • ErbB Receptors
  • Daptomycin