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

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.

• Authors: Oriana Simonetti, Oscar Cirioni, Guendalina Lucarini, Fiorenza Orlando, Roberto Ghiselli, Carmela Silvestri, Lucia Brescini, Marco Rocchi, Mauro Provinciali, Mario Guerrieri, Roberto Di Primio, Andrea Giacometti, Annamaria Offidani
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 67 Issue 1 Pg. 191-201 (Jan 2012) ISSN: 1460-2091 [Electronic] England
• PMID: 22065244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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