The Topical Evolution: Free Ions, Orthomolecular Agents, Phytochemicals, and Insect-Produced Substances.

Significance: A variety of topical antiseptic substances have been used historically to treat open wounds with suspected tissue infection or that are slow to heal. However, the effectiveness of these substances in treating infected or recalcitrant wounds remains controversial. Recent Advances: Newly formulated topical antiseptics delivered through differing dressing technologies, such as ionic substances, hold the potential to limit the development of and treat antibiotic-resistant microbes in open wounds. Other topically delivered substances, such as insect-derived substances, orthomolecular agents, and phytochemicals, also present opportunities to optimize wound healing by decreasing tissue bioburden and facilitating the wound healing process. Critical Issues: Limited systemic perfusion of open wounds in individuals with certain diagnoses, such as peripheral arterial disease or necrotizing infection and the increasing number of antibiotic-resistant wound pathogens, suggests a continued role for topically applied antiseptic agents. Likewise, the failure of wounds to heal when treated with standard of care therapy opens the door to innovative treatment approaches that include the natural substances described in this article. Future Directions: Evidence for the use of select topical antiseptic agents from each of the aforementioned categories will be discussed in this article. Additional well-controlled clinical studies are needed to provide definitive recommendations for many of these topical agents.