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Treatments that reduce <jats:italic>S. aureus<\/jats:italic> colonization without significantly affecting the skin commensal microbiota are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and findings<\/jats:title><jats:p>In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce <jats:italic>S. aureus<\/jats:italic> and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double\u2010blind and placebo\u2010controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on <jats:italic>S. aureus<\/jats:italic> colonization and skin microbiome composition in patients with mild\u2010to\u2010severe AD (EudraCT:2016\u2010003501\u201033). ATx201 has a narrow minimal inhibitory concentration distribution (.125\u2013.5\u00a0\u03bcg\/ml) consistent with its mode of action \u2013 targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin\u2010resistant <jats:italic>S. aureus<\/jats:italic>. In a Phase 2 trial in patients with mild\u2010to\u2010severe AD (<jats:italic>N<\/jats:italic> = 36), twice\u2010daily treatment with ATx201 OINTMENT 2% effectively reduces <jats:italic>S. aureus<\/jats:italic> colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, <jats:italic>p<\/jats:italic> = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.790","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T20:01:19Z","timestamp":1651867279000},"source":"Crossref","is-referenced-by-count":51,"title":["Topical niclosamide (ATx201) reduces <i>Staphylococcus aureus<\/i> colonization and increases Shannon diversity of 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