The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis

• Published in: British journal of dermatology (1951) Vol. 179; no. 4; pp. 951 - 958
• Main Authors: Harkins, C.P., McAleer, M.A., Bennett, D., McHugh, M., Fleury, O.M., Pettigrew, K.A., Oravcová, K., Parkhill, J., Proby, C.M., Dawe, R.S., Geoghegan, J.A., Irvine, A.D., Holden, M.T.G.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.10.2018; John Wiley and Sons Inc
• Subjects: Antimicrobial agents; Antimicrobial resistance; Antiseptics; Atopic dermatitis; Children; Dermatitis; Eczema; Fusidic acid; General Dermatology; Genomes; Genotypes; Original; Phenotypes; Phylogeny; Skin diseases; Staphylococcus aureus
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.16722

Summary Background Carriage rates of Staphylococcus aureus on affected skin in atopic dermatitis (AD) are approximately 70%. Increasing disease severity during flares and overall disease severity correlate with increased burden of S. aureus. Treatment in AD therefore often targets S. aureus with topical and systemic antimicrobials. Objectives To determine whether antimicrobial sensitivities and genetic determinants of resistance differed in S. aureus isolates from the skin of children with AD and healthy child nasal carriers. Methods In this case–control study, we compared S. aureus isolates from children with AD (n = 50) attending a hospital dermatology department against nasal carriage isolates from children without skin disease (n = 49) attending a hospital emergency department for noninfective conditions. Using whole genome sequencing we generated a phylogenetic framework for the isolates based on variation in the core genome, then compared antimicrobial resistance phenotypes and genotypes between disease groups. Results Staphylococcus aureus from cases and controls had on average similar numbers of phenotypic resistances per isolate. Case isolates differed in their resistance patterns, with fusidic acid resistance (FusR) being significantly more frequent in AD (P = 0·009). The genetic basis of FusR also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that FusR evolved multiple times and via multiple mechanism in the population. Carriage of plasmid‐derived qac genes, which have been associated with reduced susceptibility to antiseptics, was eight times more frequent in AD (P = 0·016). Conclusions The results suggest that strong selective pressure drives the emergence and maintenance of specific resistances in AD. What's already known about this topic? Staphylococcus aureus frequently colonizes individuals with atopic dermatitis (AD), with increasing disease severity correlating with greater bacterial load of the organism. Antimicrobial therapies are routinely used in AD for management and prevention of disease flares. What does this study add? Staphylococcus aureus isolates from children with AD differ in their antimicrobial resistance profiles from those in healthy, nonatopic nasally colonized children. Fusidic acid resistance is significantly more prevalent in cases of AD, and arises through distinct genetic mechanisms when compared with healthy controls. Carriage of plasmid‐derived genetic determinants associated with antiseptic resistance also clearly differentiated S. aureus from cases of AD and controls. Linked Editorial: Leung. Br J Dermatol 2018; 179:807–808. Plain language summary available online Respond to this article