Targeted Prevention or Treatment of Bacterial Biofilm Infections of Severe Burns and Wounds
Abstract
Findings to date support the hypothesis that a dual therapeutic approach of targeted anti-inflammation and a biofilm specific antibiotic will significantly limit severe Pseudomonas aeruginosa infection associated with serious burns and wounds. A 12-mer N2 peptide was synthesized to bind and competitively inhibit IgMCM-22 that recognizes self antigens on the nonmuscle myosin heavy chain II (NMHC-II) that are exposed at the time of injury. An optimal dosing strategy was determined that utilizes the combination of topical administration at the burn site and intravenous tail vein injection. The effect of N2 peptide in limiting neutrophil influx to the injury site was dramatic at 4 hours, however, the effect was no longer present by 48 hours, despite repeated N2 dosing. Nonetheless, the initial disruption of neutrophil influx was sufficient to significantly reduce inflammatory changes at the histological level, and gross tissue injury 48 hours later. When P. aeruginosa was applied to the burn site 2 hours after injury, the N2 peptide demonstrated a similar effect in reducing early inflammation, but not in reducing later neutrophil influx despite repeated dosing. However, this effect was sufficient to result in a significant reduction in P. aeruginosa infection of the burn. These results prove that by briefly stopping the influx of neutrophils to the site of thermal injury, the subsequent wound severity is decreased and growth of P. aeruginosa delayed. With the addition of azithromycin into this model, we fully expect that this infection reducing strategy will be substantially improved.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2010
- Accession Number
- ADA540955
Entities
People
- Jerry A. Nick
Organizations
- National Jewish Health