OBJECTIVES: Community-associated methicillin-resistant Staphylococcus aureus is responsible for an increasing number of skin infections. Over-the-counter topical wound care products may play a role in the prevention of these infections, but limited data are available regarding their activity. The current study utilized a modified time-kill design to evaluate the activity of three over-the-counter topical wound care products (benzethonium chloride/essential oils, neomycin/polymyxin B and polymyxin B/gramicidin) against four unique isolates (three USA 300 and one USA 400). METHODS: All experiments were performed using commercially available formulations. Bactericidal activity was defined as a sustained 3 log(10) reduction in cfu/mL from the initial inoculum. Reductions in bacterial counts between agents were determined using analysis of variance. RESULTS: At 10 min, the reduction (mean +/- SD) in log(10) cfu/mL for all strains was 2.87 +/- 1.22, 1.86 +/- 0.76 and 0.143 +/- 0.82 for benzethonium chloride/essential oils, neomycin/polymyxin B and polymyxin B/gramicidin, respectively. By 24 h, bactericidal activity was observed against two strains each for neomycin/polymyxin B and polymyxin B/gramicidin. Benzethonium chloride/essential oils was bactericidal against all strains by 6 h. At 24 h, all three agents were superior to controls (P < 0.05). Benzethonium chloride/essential oils was more active at 24 h than polymyxin B/gramicidin versus all four strains (P < 0.05) and more active than neomycin/polymyxin B versus three of four strains (P < 0.05). CONCLUSIONS: These topical agents demonstrated variable activity against the four strains tested. Benzethonium chloride/essential oils was more rapidly and completely active than the other agents tested.