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Can antibiotics be harmful in atopic dermatitis?

Atopic dermatitis (AD) is a pruritic chronic inflammatory skin disease associated with Staphylococcus aureus colonization. This is a clinically significant finding because S. aureus colonization is associated with increased AD severity, a more allergic diathesis and skin-barrier dysfunction. This propensity toward S. aureus colonization is complex but begins with attachment of S. aureus to bacterial adhesion sites within the skin. Importantly, these S. aureus adhesion sites, such as fibronectin, are induced by type 2 cytokines such as interleukin (IL)-4 and IL-13. Type 2 cytokines reduce filaggrin, lipids and antimicrobial peptides required to control S. aureus growth thereby allowing S. aureus to proliferate and reach high numbers in atopic skin with significant barrier dysfunction. Recent studies reveal that S. aureus produce virulence factors, including lipases and proteases that damage the skin barrier. Furthermore, exposure of keratinocytes to IL-4 and IL-13 make them more susceptible to the deleterious effects of S. aureus toxins. Antibiotics are commonly used as part of the management of AD. However, only a minority of patients with AD have clinically significant invasive skin and systemic S. aureus infection. Interestingly, a Cochrane review concluded that data was lacking for highly beneficial outcomes with exclusive use of antibiotics in the management of AD. This is consistent with studies dating back to the early 1970s by Leyden and Kligman that patients with AD primarily benefit from antibiotics when they are colonized with more than one million bacteria per cm of skin. Therefore, in the absence of an exudative or crusted skin lesion, the usefulness of antibiotics can be debated and their ability to completely eliminate S. aureus colonization is dubious. In the current issue of the BJD, Harkins and colleagues report, in a case-controlled study, that S. aureus skin isolates from children with AD differ in their antimicrobial resistance profiles from those from healthy, nonatopic nasally colonized children. In particular, fusidic acid resistance is significantly more prevalent in individuals with AD and arises through distinct genetic mechanisms when compared with healthy controls. This high prevalence of fusidic acid resistance likely results from the common use of topical fusidic acid in Northern Europe for treatment of S. aureus skin infection or colonization. In contrast, mupirocin resistance was relatively low in the AD and control groups likely because of comparatively low usage of this topical antibiotic in Ireland. In parts of the world, for example the U.S.A., where fusidic acid is rarely used, resistance to fusidic acid is uncommon because of the lack of selective pressures for such antimicrobial-resistant bacteria to evolve. On the other hand, mupirocin resistance has been found to be high in centres from the U.S.A. with AD and methicillin-resistant S. aureus (MRSA) listed as risk factors. MRSA prevalence was also low in the Harkins et al. study. MRSA, in particular, has become an increasing concern worldwide because of its overall morbidity and mortality in addition to its common prevalence worldwide. A recent study found that MRSA colonization was highly invasive establishing a dominant presence in its niche with crowding out of commensal or beneficial bacteria. The study design of Harkins et al.’s study does raise some questions that should be considered. Firstly, the AD skin cultures were obtained between September 2012 and September 2014, whereas the nasal cultures from controls were obtained from July to August 2009. The occurrence of increased resistance in skin compared with nasal isolates may occur from different selection pressures including use of topical antibiotics on the skin vs. less frequent use in the nose. However, a previous study, by these investigators had shown intermingling of S. aureus isolates from nasal and skin cultures of patients with AD suggesting a lack of clonal aggregation in the two tissues. There is also a minor concern that antibiotic resistance profiles can change over time. A prospective multicentre study, in the future, collecting contemporaneous case and control samples is important to rule out confounding factors. Secondly, it is assumed that patients used topical fusidic acid before as treatment. However, the factors leading to selection for fusidic acid resistance were not determined in this study. Any future study should include questions of patients regarding prior treatment or examine prescription records of patients being prospectively cultured. The overall objective of this study was, nevertheless, to characterize resistance patterns within S. aureus isolates from an AD vs. a control group at a population level and the data clearly demonstrate evidence for increased antimicrobial resistance in skin isolates from patients with AD. These observations have important clinical implications, as they suggest that our clinical management of AD has an important influence on the skin microbiome. In this regard, the current study suggests prior antibiotic use is an important selection pressure for antibiotic-resistant bacteria and their overuse could lead to difficulties managing serious infections. The results highlight the importance of antimicrobial monitoring in AD. In the future, we have to consider if the use of any antibiotic is warranted in all cases of AD flare or only when exudative infection is observed. Indeed, studies suggest a midstrength potency topical corticosteroid or calcineurin inhibitors can reduce S. aureus colonization even in the absence of antibiotics. These data suggest that in mild AD disease