Improvement in survival with peptidyl membrane interactive molecule D4B treatment after burn wound infection.
OBJECTIVE
To examine the effects of peptidyl membrane interactive molecule D4B in a murine model of lethal burn wound infection.


METHODS
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.


METHODS
University medical center laboratory.


METHODS
Groups of B6D2F1 male mice (20 each) were studied.


METHODS
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.


METHODS
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.
Burn and Shock Trauma Institute and Department of Surgery, Loyola University Medical Center, Maywood, Ill 60153, USA. rgamell@wpo.it.luc.ed
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Gamelli
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Liu
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Ricken
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001798:Blood Proteins / Q000627:therapeutic use*; D002056:Burns / Q000150:complications / Q000401:mortality*; D023082:Defensins; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate; D014946:Wound Infection / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality*
D000890:Anti-Infective Agents; D001798:Blood Proteins; D023082:Defensins