Improvement in burn wound infection and survival with antimicrobial peptide D2A21 (Demegel).
Naturally occurring antimicrobial peptides have been discovered in both plants and animals. Many of these peptides demonstrate impaired activity or cytotoxicity when applied exogenously. Synthetically engineered antimicrobial peptides have been designed to increase potency and activity against bacteria and fungus yet remain noncytotoxic. The antimicrobial peptide D2A21 (Demegel) has already demonstrated significant activity in vitro against many common hospital pathogens. The purpose of this study was to evaluate the effects of D2A21 in an in vivo infected burn-wound model, examining both quantitative cultures of the wound and survival of the animal. Forty-four Wistar rats were subjected to a 23 percent total body surface area scald burn. Pseudomonas aeruginosa was administered topically with 108 organisms and wounds were then evaluated at day 1, 2, or 3 for eschar and subeschar muscle quantitative culture. The experimental group was treated daily with 1.5% topical D2A21. The control group was treated with control gel. A second group of Wistar rats (n = 14) were burned and given a 107 inoculum of the same Pseudomonas and evaluated to 14 days for survival and weight changes. This group was subdivided into rats receiving either topical D2A21 or control base daily. The quantitative biopsy results demonstrated that D2A21-treated wounds had no bacterial growth in burn eschar at day 2 or 3, whereas control animals demonstrated growth at greater than 105 organisms by day 2. Subeschar muscle cultures also demonstrated significantly less bacterial invasion compared with controls on each day tested. D2A21-treated animals had an 85.7 percent survival compared with 0 percent survival in controls. Furthermore, the D2A21-treated groups demonstrated maintenance of body weights, whereas controls had significant weight loss with time. In conclusion, D2A21 demonstrates significant antibacterial activity against Pseudomonas, sterilizing burn eschar and decreasing subeschar bacterial load, allowing for a markedly significant improvement in survival in this infected burn-wound model.
Chalekson
Charles P
CP
Plastic Surgery Institute, Southern Illinois University School of Medicine, Springfield. IL 62794, USA.
Neumeister
Michael W
MW
Jaynes
Jesse
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D002056:Burns / Q000150:complications* / Q000401:mortality; D004195:Disease Models, Animal; D008297:Male; D010455:Peptides; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014946:Wound Infection / Q000188:drug therapy* / Q000401:mortality
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C430264:D2A21; D010455:Peptides