1621. Novel Antimicrobial Block Copolypeptides for the Prevention and Treatment of Local Infections
Session: Poster Abstract Session: Novel Antimicrobial Agents
Saturday, October 20, 2012
Room: SDCC Poster Hall F-H
Background: Local bacterial and fungal infections complicate a variety of wounds that include surgical sites, burns, and diabetic foot ulcers. They present special challenges that include damaged tissues, biofilm formation, and inadequate blood flow, all of which may result in failure to achieve therapeutic antimicrobial levels. New approaches to local antimicrobials are needed.

Methods: We have developed novel long-chain, lysine-leucine block copolypeptides that are broadly antimicrobial and that self-assemble into hierarchical structures (e.g. micelles, fibrils) to coat tissues effectively. These cationic antimicrobial biomaterials can be engineered to form a variety of solutions and gels. They can be applied directly to wounds to reduce bacterial burden, as well as to form a temporary antimicrobial barrier to reduce infection.

Results: Antimicrobial activity of a block copolypeptide solution and gel were investigated in vitro and in vivo. In 30 minute time-kill assays in vitro, both demonstrated broad-spectrum antimicrobial activity (4+ log reduction) against Gram-positive (S. aureus, S. epidermidis) and Gram-negative (E. coli, P. aeruginosa) bacteria. In pilot in vivo studies, both solution and gel blocked infection. In a rodent closed-wound model with foreign body, mesh was inserted subcutaneously into Sprague-Dawley rats, followed by antimicrobial solution or gel. An inoculum of 107 S. aureus was added and wounds were closed. After 2 days, the block copolypeptide solution and gel both substantially decreased bacteria compared to controls (4+ log reduction). In a porcine open-wound model, full-thickness 1cm diameter wounds were made in the dorsal and lateral thorax of Yorkshire-cross pigs. Solution or gel was applied, and after 4 hours, wounds were inoculated with 107 S. aureus. After 2 days, both fully reduced bacterial burden (4+ log reduction). Preliminary wound healing studies suggest biocompatibility.

Conclusion: Taken together, these studies suggest that novel lysine-leucine block copolypeptide solutions and gels are broadly antimicrobial, effective in contaminated wound models, and biocompatible with tissues. Direct application to wounds could significantly help in preventing and treating local infections.

Janet Chow, Ph.D., Jarrod Hanson, Ph.D., Diego Benitez, Ph.D., Kevin Ogilby, B.S. and Michael Bevilacqua, M.D., Ph.D., Amicrobe, Inc., Pasadena, CA

Disclosures:

J. Chow, Amicrobe, Inc.: Employee, Salary

J. Hanson, Amicrobe, Inc.: Employee, Salary

D. Benitez, Amicrobe, Inc.: Employee, Salary

K. Ogilby, Amicrobe, Inc.: Employee, Salary

M. Bevilacqua, Amicrobe, Inc.: Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 17th with the exception of research findings presented at the IDWeek press conferences.