Synergistic Combination of Chitosan Acetate with Nanoparticle Silver as a Topical Antimicrobial: Efficacy against Bacterial Burn Infections

Abstract

ABSTRACTChitosan and nanoparticle silver are both materials with demonstrated antimicrobial properties and have been proposed singly or in combination as constituents of antimicrobial burn dressings. Here, we show that they combine synergistically to inhibit thein vitrogrowth of Gram-positive methicillin-resistantStaphylococcus aureus(MRSA) and Gram-negative bacteria (Pseudomonas aeruginosa,Proteus mirabilis, andAcinetobacter baumannii), as judged by bioluminescence monitoring and isobolographic analysis, and also produce synergistic killing after 30 min of incubation, as measured by a CFU assay. The hypothesized explanation involves chitosan-mediated permeabilization of bacterial cells, allowing better penetration of silver ions into the cell. A dressing composed of freeze-dried chitosan acetate incorporating nanoparticle silver was compared with a dressing of chitosan acetate alone in anin vivoburn model infected with bioluminescentP. aeruginosa. The survival rates of mice treated with silver-chitosan or regular chitosan or left untreated were 64.3% (P= 0.0082 versus regular chitosan andP= 0.0003 versus the control), 21.4%, and 0%, respectively. Most of the fatalities occurred between 2 and 5 days postinfection. Silver-chitosan dressings effectively controlled the development of systemic sepsis, as shown by blood culture. These data suggest that a dressing combining chitosan acetate with silver leads to improved antimicrobial efficacy against fatal burn infections.