Tigecycline accelerates staphylococcal-infected burn wound healing through matrix metalloproteinase-9 modulation

J Antimicrob Chemother. 2012 Jan;67(1):191-201. doi: 10.1093/jac/dkr440. Epub 2011 Nov 6.

Abstract

Objectives: We investigated the in vivo efficacy of tigecycline, a new glycylcycline (a tetracycline derivative), in the management of methicillin-resistant Staphylococcus aureus (MRSA)-infected experimental surgical wounds in rats. The main outcome measures were quantitative bacterial culture, histological examination and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9) and collagen IV.

Methods: An animal model was used to compare the in vivo efficacy of teicoplanin and tigecycline in the treatment of burn wound infections by S. aureus. A copper bar, heated in boiling water, was placed on the paraspinal site of each rat, resulting in full thickness burns. A small gauze was placed over each burn and then inoculated with 5 × 10(7) cfu of S. aureus ATCC 43300. To mimic the clinical situation in burn patients, surgical debridement was performed 48 h after the injury. The wounds were left to heal by secondary intention. The study included an uninfected control group that did not receive any treatment, a contaminated group that did not receive any treatment, and two contaminated groups treated with intraperitoneal tigecycline (2 mg/kg) and teicoplanin (7 mg/kg), respectively.

Results: All antibiotic treatments were significantly effective. Tigecycline showed the highest antimicrobial activity, with a better impact on histological results. Infected rats treated with tigecycline showed a significant decrease in MMP-9 expression both in epithelium and in dermis compared with rats treated with teicoplanin.

Conclusions: Tigecycline, besides its antimicrobial activity, exerts an important modulatory effect on MMP-9, accelerating wound healing in staphylococcal-infected burns.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Load
  • Burns / complications*
  • Disease Models, Animal
  • Histocytochemistry
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Minocycline / administration & dosage
  • Minocycline / analogs & derivatives*
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Teicoplanin / administration & dosage
  • Tigecycline
  • Treatment Outcome
  • Wound Healing*
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology

Substances

  • Matrix Metalloproteinase Inhibitors
  • Teicoplanin
  • Tigecycline
  • Matrix Metalloproteinase 9
  • Minocycline