To the Editor: Staphylococcus aureus density is increased in many patients with atopic dermatitis (AD) and is thought to contribute to disease pathogenesis, interacting with an altered skin barrier and immunologic changes.1 S aureus might induce or aggravate inflammation through different mechanisms, for example through excretion of virulence factors, even if the S aureus overgrowth is primarily caused by other factors.2 Current guidelines only recommend antimicrobial therapy directed against S aureus in patients with clinically infected AD based on a Cochrane review in which no clinical benefit of short-term antimicrobial treatment in patients with noninfected AD was found.3 Arguably, long-term antistaphylococcal treatment, such as antibiotics, might reduce symptoms in patients with AD.4 However, this is undesired because antibiotics can affect the commensal microbiota and could induce bacterial resistance.5 In contrast, long-term treatment of AD with an endolysin that targets only S aureus is feasible. Clinical efficacy was measured by using the Eczema Area and Severity Index, Investigators Global Assessment, Patient-Oriented Eczema Measure, and pruritus Numeric Rating Scale and by registration of the number of flares. ...daily use of an emollient and good compliance with the treatment could have resulted in a reduction in triamcinolone use in both the endolysin and vehicle groups.7 Because AD is a heterogeneous disease, anti–S aureus treatment might not be suitable for all patients with AD, indicating the need for subphenotyping. Because only 56% of our study population had 2 consecutive positive S aureus skin cultures (indicating persistent colonization) before the start of the intervention, the target population that would probably benefit the most from endolysin treatment was small. ...long-term targeted endolysin treatment against S aureus in this study was well tolerated but had no TCS-sparing effect in patients with AD.