d2a21 and Pseudomonas-Infections

Infected wounds impose a significantly negative effect on patient care and recovery, as infection hinders normal wound healing, resulting in increased patient morbidity and mortality. More attention is being focused on addressing the problem of multidrug-resistant bacteria and the staggering costs and consequences resulting from this. Recently, newly evaluated antimicrobial peptides have been shown to be active against a wide variety of bacteria in in vitro studies. This study evaluates the use of a particular antimicrobial peptide, D2A21 (Pittsburgh, PA), to combat infection in an acutely infected wound model.. Forty-eight Wistar rats were used to compare the effects of D2A21 to control vehicle, silver sulfadiazine (SSD), and Sulfamylon in this model. Two 1.5 x 1.5-cm full-thickness defects were created on the rat dorsum and were subsequently inoculated with 108 Pseudomonas aeruginosa. Animals underwent daily treatment with either D2A21 gel, control vehicle, SSD, or Sulfamylon. Animals were evaluated for survival differences.. Survival analysis at 21 days for the different treatment groups were as follows: 100% for the D2A21-treated animals, 50% for control-treated animals, 83% for Sulfamylon-treated animals, and 33% for SSD-treated animals.. D2A21 antimicrobial peptide demonstrates significant activity compared with controls and standards of therapy. The promising effect of this topical peptide is clearly evident as shown by this study, and its further investigation as a potential agent in the fight against infected or chronic wounds is warranted.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Burns; Chi-Square Distribution; Disease Models, Animal; Male; Peptides; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Wistar; Survival Analysis; Wound Infection

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.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides; Burns; Disease Models, Animal; Male; Peptides; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Wistar; Wound Infection