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The use of light-activated bactericidal agents—photobactericides—is suggested in local infection in order to conserve conventional antibacterials for more systemic disease. Local administration of a photobactericide such as methylene blue coupled with locally-targeted red light illumination ensures the production of non-specific reactive oxygen species and thus a rapid and localised antibacterial response, regardless of the conventional resistance status. To this end, the response of photobactericides to conventional resistance mechanisms, and their potential use in infection, is discussed.