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Richard L. Gamelli, MD; Li-Ke He, MD; Hong Liu, MD; John D. Ricken, BS

Arch Surg. 1998;133:715-720.

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 µmol/L; (2) in vitro coculture of bone marrow cells with D4B, 0 to 100 µmol/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 µg 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.

From the Burn and Shock Trauma Institute and Departments of Surgery (Drs Gamelli and He and Mr Ricken) and Pathology (Dr Liu), Loyola University Medical Center, Maywood, Ill.

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