SELECTION OF TOPICAL ANTIMICROBIAL AGENTS FOR CULTURED SKIN FOR BURNSBY COMBINED ASSESSMENT OF CELLULAR CYTOTOXICITY AND ANTIMICROBIAL ACTIVITY

Cultured epidermal skin has become an adjunctive therapy for treatment of major burn injuries, but its effectiveness is greatly limited due to destruction by microbial contamination. To evaluate candidate drugs for use with cultured skin, a combined cytotoxicity-antimicrobial ass ay system was developed for determination of toxicity to cultured huma n keratinocytes and fibroblasts, and to common burn wound organisms (2 0 bacterial and 4 fungal strains). Candidate agents including Hibiclen s (n = 3), amikacin, piperacillin, norfloxacin, and nystatin were test ed separately and in combination (n = 6 each) for inhibition of growth of human cells and lytic activity on microorganisms in the wet disc a ssay. The data showed that: (1) Hibiclens was uniformly toxic to both cultured human cells and microorganisms; (2) norfloxacin had dose-depe ndent toxicity to human cells and broad effectiveness against microorg anisms; and (3) norfloxacin (25 mug/mL) plus nystatin (100 U/mL) had l ow toxicity to human cells and high toxicity to both Gram-positive and Gram-negative bacteria (20 of 20) and fungi (4 of 4). Selection of to pical antimicrobial drugs by these assays may improve effectiveness of cultured skin for burns and may be extended to the control of other s urgical wound infections.