846 Effects of Ceragenins on Pseudomonas Aeruginosa Biofilm Formation in Burn Wounds in a Porcine Model

Abstract

Abstract Introduction Damage from burn wounds compromises the protective function of the skin, increasing susceptibility to bacterial and fungal infections and sepsis. Pseudomonas aeruginosa is commonly infects burn injuries and is associated with high morbidity, especially in large total burn surface area injuries. Silver sulfadiazine (SSD), the standard topical antimicrobial used for burn wounds, has been associated with irritation, scarring and other adverse effects creating a need for alternative treatment options. Ceragenins are small-molecule mimics of endogenous antimicrobial peptides. In this pilot study, two ceragenins, CSA-44 and CSA-144 were assessed for their ability to reduce P. aeruginosa in a porcine burn wound model. Methods One pathogen-free female pig was appropriately prepared and 48 burn wounds were generated, under general anesthesia, on the back and flank area by direct contact with a heated brass rod. Wounds were inoculated with P. aeruginosa and biofilm was allowed to form for 24 hours. Four of the wounds were analyzed 24 hours post inoculation to establish baseline bacterial counts. R emaining wounds were treated with a vehicle control, SSD (positive control) or formulations of CSA-44 and CSA-144 in gel, cream and aqueous forms. After 7 days of treatment, tissue samples from the wounds were excised and bacterial counts were determined (colony forming units per milliliter of tissue). Percent decreases in bacterial counts were evaluated for each wound. The wounds were also observed for erythema and irritation over the course of the study. Results The greatest reductions in bacterial counts after treatment were seen in wounds treated with aqueous CSA-44 at 0.05 % (99.6% reduction) and aqueous CSA-144 at 0.05% (98.4% reduction), which were both greater than the bacterial reductions seen in wounds treated with SSD. Additionally, after the second day of treatment, wounds treated with aqueous CSA-44 and CSA-144 showed reduced erythema, while wounds treated with SSD continued to show swelling and redness. Conclusions This study demonstrates the effective antimicrobial action of aqueous formulations of ceragenins CSA-44 and CSA-144. The bacterial reduction seen with aqueous CSA-44 and CSA-144 were greater than the positive control (SSD). Furthermore, treatment with CSA-44 showed reduced signs of irritation, which were not observed with SSD. Even within this small sample size, the superior antimicrobial ability of ceragenins, without the negative effects of SSD becomes apparent. Applicability of Research to Practice Ceragenins provide a means of replacing endogenous defenses against infection in burn wounds.