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Abstract Although evidence showing that Staphylococcus aureus (S. aureus) is directly causative of atopic dermatitis (AD) is still lacking, there is evidence that S. aureus abundance is associated with disease flares and therapeutic responses. Patients receiving ATx201 OINTMENT 2% twice‐daily had a significant reduction in the abundance of S. aureus and increasing Shannon diversity of skin microbiome compared to vehicle after seven days. A small molecule with a narrow‐spectrum effect, especially on S. aureus, might be an attractive alternative for the treatment of AD.