IMPROVEMENT IN SURVIVAL WITH PEPTIDYL MEMBRANE INTERACTIVE MOLECULE D4B TREATMENT AFTER BURN WOUND INJECTION

Objective: To examine the effects of peptidyl membrane interactive mol ecule D4B in a murine model of lethal burn wound infection. Experiment al Design: Four experiments were performed: (1) growth inhibition assa ys of Pseudomonas aeruginosa treated with D4B, 0 to 100 mu moVL; (2) i n vitro coculture of bone marrow cells with D4B, 0 to 100 mu moVL; (3) D4B treatment survival studies after burn injury only or burn wound i nfection in mice; and (4) peripheral white blood cell count, burn woun d tissue bacterial culture, and burn wound morphological analysis at d ays 1, 2, and 3 after injury. Setting: University medical center labor atory. Subjects: Groups of B6D2F1 male mice (20 each) were studied. In terventions: Full-thickness scald burn, 15% of total body surface area , with P aeruginosa topical infection, and subeschar injections of D4B at 200 mu g or 0.25 mt of placebo per mouse at 2 and 24 hours after i njury. Main Outcome Measures: Animal survival after thermal burn wound bacterial infection, circulating leukocyte numbers, in vitro clonal c ell culture of granulocyte-macrophage progenitor cells, and wound hist opathological analysis. Results: The survival rate in the D4B-treated group was nearly 2-fold greater than that in controls (P<.01) during 1 4 days of study. Bacterial quantitative wound cultures disclosed signi ficant reductions in bacterial numbers at days 1, 2, and 3 in D4B-trea ted animals as compared with controls (P<.05 to <.01). D4B induced a d ose dependent inhibition of bacterial cell growth when added to in vit ro P aeruginosa cultures (P<.01). Granulocyte macrophage progenitor ce ll growth in culture was not altered by D4B treatment. D4B-treated ani mals displayed no signs of toxic effects or impairment in wound healin g. 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.