Antibacterial Efficacy of a Chitosan-Based Hydrogel Modified With Epsilon-Poly-l-Lysine Against Pseudomonas aeruginosa in a Murine-Infected Burn Wound Model.

INTRODUCTION: Because antibiotic resistance is increasing worldwide and the leading cause of death in burn patients is an infection, an urgent need exists for nonantibiotic approaches to eliminate multidrug-resistant bacteria from burns to prevent their systemic dissemination and sepsis. We previously demonstrated the significant antibiofilm activity of a chitosan (CS) hydrogel containing the antimicrobial peptide epsilon-poly-l-lysine (EPL) against multidrug-resistant Pseudomonas aeruginosa using ex vivo porcine skin. In this study, we evaluated the in vivo antibacterial efficacy of a CS/EPL hydrogel against P. aeruginosa in a murine burn wound infection model. MATERIALS AND METHODS: Full-thickness burns were created on the dorsum using a heated brass rod and were inoculated with bioluminescent, biofilm-forming P. aeruginosa (Xen41). Mice were treated with CS/EPL, CS, or no hydrogel applied topically 2 or 24 hours after inoculation to assess the ability to prevent or eradicate existing biofilms, respectively. Dressing changes occurred daily for 3 days, and in vivo bioluminescence imaging was performed to detect and quantitate bacterial growth. Blood samples were cultured to determine systemic infection. In vitro antibacterial activity and cytotoxicity against human primary dermal fibroblasts, keratinocytes, and mesenchymal stem cells were also assessed. RESULTS: CS/EPL treatment initiated at early or delayed time points showed a significant reduction in bioluminescence imaging signal compared to CS on days 2 and 3 of treatment. Mice administered CS/EPL had fewer bloodstream infections, lower weight loss, and greater activity than the untreated and CS groups. CS/EPL reduced bacterial burden by two orders of magnitude in vitro and exhibited low cytotoxicity against human cells. CONCLUSION: A topical hydrogel delivering the antimicrobial peptide EPL demonstrates in vivo efficacy to reduce but not eradicate established P. aeruginosa biofilms in infected burn wounds. This biocompatible hydrogel shows promise as an antimicrobial barrier dressing for the sustained protection of burn wounds from external bacterial contamination.

Time to weigh in on obesity and associated comorbidities in combat-wounded amputees.

BACKGROUND: The Joint Trauma System database estimates that about 1,200 individuals have sustained a combat-related amputation during the Global War on Terror. Previous retrospective studies have demonstrated that combat-related amputees develop obesity and cardiovascular disease, but the incidence of obesity and associated comorbidities in this population is unknown. The objectives of this study are to determine the prevalence of obesity in the military amputee population and to compare this with the general population. METHODS: This is a retrospective review of 978 patients who sustained a combat-related amputation from 2003 to 2014. Prevalence of obesity and comorbid conditions were determined. A multivariate logistic regression model was performed to identify risk factors for postamputation obesity. Kaplan-Meier curves were constructed using obesity as the event of interest. RESULTS: A total of 1,233 charts were reviewed with 978 patients included for analysis. The median age of injury was 24 years. Median follow-up time was 8.7 years, ranging from 0.5 years to 16.9 years. The average Injury Severity Score was 23.3. The average body mass index preinjury was 25.6 kg/m2, and the average most recent corrected body mass index was found to be 31.4 kg/m2. Prevalence of comorbidities was higher in the amputee population. Fifty percent of patients who progressed to obesity did so within 1.3 years. CONCLUSION: There is a notable prevalence of obesity that develops in the amputee population that is much higher than the general population. We determined that the amputee population is at risk, and these patients should be closely monitored for 1 to 2.5 years following injury. This study provides a targeted period for which monitoring and intervention can be implemented. LEVEL OF EVIDENCE: Retrospective, basic science, outcomes analysis, level III/IV.