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Improvement in survival with peptidyl membrane interactive molecule D4B treatment after burn wound infection
1Burn and Shock Trauma Institute and Department of Surgery, Loyola University Medical Center, Maywood, Ill 60153, USA. rgamell@wpo.it.luc.ed
Objective:
To examine the effects of peptidyl membrane interactive molecule D4B in a murine model of lethal burn wound infection.
Experimental Design:
Four experiments were performed: (1) growth inhibition assays of Pseudomonas aeruginosa treated with D4B, 0 to 100 micromol/L; (2) in vitro coculture of bone marrow cells with D4B, 0 to 100 micromol/L; (3) D4B treatment survival studies after burn injury only or burn wound infection in mice; and (4) peripheral white blood cell count, burn wound tissue bacterial culture, and burn wound morphological analysis at days 1, 2, and 3 after injury.
Setting:
University medical center laboratory.
Subjects:
Groups of B6D2F1 male mice (20 each) were studied.
Interventions:
Full-thickness scald burn, 15% of total body surface area, with P aeruginosa topical infection, and subeschar injections of D4B at 200 microg or 0.25 mL of placebo per mouse at 2 and 24 hours after injury.
Main Outcome Measures:
Animal survival after thermal burn wound bacterial infection, circulating leukocyte numbers, in vitro clonal cell culture of granulocyte-macrophage progenitor cells, and wound histopathological analysis.
Results:
The survival rate in the D4B-treated group was nearly 2-fold greater than that in controls (P<.01) during 14 days of study. Bacterial quantitative wound cultures disclosed significant reductions in bacterial numbers at days 1, 2, and 3 in D4B-treated animals as compared with controls (P<.05 to <.01). D4B induced a dose-dependent inhibition of bacterial cell growth when added to in vitro P aeruginosa cultures (P<.01). Granulocyte-macrophage progenitor cell growth in culture was not altered by D4B treatment. D4B-treated animals displayed no signs of toxic effects or impairment in wound healing.
Conclusions:
The peptidyl membrane interactive molecule D4B had the ability to improve survival after gram-negative burn wound sepsis via direct antimicrobial effects. Peptidyl membrane interactive molecules may offer the potential of alternative treatments to standard topical agents or in patients with drug-resistant microbes.
Insights
The peptidyl molecule D4B significantly improved survival in mice with burn wound infections by directly inhibiting bacterial growth. This molecule shows promise as an alternative treatment for drug-resistant infections.
Area of Science:
- Microbiology
- Immunology
- Wound Healing
Background:
- Burn wound infections, particularly those caused by Gram-negative bacteria like Pseudomonas aeruginosa, pose a significant threat to patient survival.
- Current treatments for burn wound sepsis face challenges due to increasing antimicrobial resistance.
Purpose of the Study:
- To evaluate the efficacy of the peptidyl membrane interactive molecule D4B in a murine model of lethal burn wound infection.
- To assess the direct antimicrobial effects and potential toxicity of D4B.
Main Methods:
- In vitro studies assessed D4B's inhibition of Pseudomonas aeruginosa growth and its effect on bone marrow cell cultures.
- In vivo studies involved inducing burn wounds in mice, infecting them with P. aeruginosa, and administering D4B or placebo.
- Outcomes measured included survival rates, bacterial load in wounds, white blood cell counts, and wound morphology.
Main Results:
- D4B treatment nearly doubled survival rates in infected mice compared to controls (P<.01).
- Significant reductions in bacterial counts were observed in D4B-treated wounds at days 1, 2, and 3 (P<.05 to <.01).
- D4B demonstrated dose-dependent inhibition of P. aeruginosa growth in vitro without affecting progenitor cell growth or causing signs of toxicity or impaired wound healing.
Conclusions:
- The peptidyl molecule D4B effectively enhances survival in burn wound sepsis through direct antimicrobial action.
- Peptidyl membrane interactive molecules represent a potential alternative therapeutic strategy for infections, including those caused by drug-resistant microbes.