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

Catriona Harkins (Lead / Corresponding author), M. A. McAleer, D. Bennett, M. McHugh, O. M. Fleury, K. A. Pettigrew, K. Oravcová, J. Parkhill, Charlotte Proby, Robert Dawe, J. A. Geoghegan, A. D. Irvine, M. T. G. Holden

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Abstract

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 (Fus R) being significantly more frequent in AD (P = 0·009). The genetic basis of Fus R also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that Fus R 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.

Original languageEnglish
Pages (from-to)951-958
Number of pages8
JournalBritish Journal of Dermatology
Volume179
Issue number4
Early online date5 May 2018
DOIs
Publication statusPublished - Oct 2018

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Atopic Dermatitis
Staphylococcus aureus
Fusidic Acid
Hospital Departments
Nose
Genome
Skin
Local Anti-Infective Agents
Dermatology
Skin Diseases
Population
Hospital Emergency Service
Plasmids
Genotype
Maintenance
Phenotype
Mutation
Genes

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Harkins, C., McAleer, M. A., Bennett, D., McHugh, M., Fleury, O. M., Pettigrew, K. A., ... Holden, M. T. G. (2018). The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis. British Journal of Dermatology, 179(4), 951-958. https://doi.org/10.1111/bjd.16722
Harkins, Catriona ; McAleer, M. A. ; Bennett, D. ; McHugh, M. ; Fleury, O. M. ; Pettigrew, K. A. ; Oravcová, K. ; Parkhill, J. ; Proby, Charlotte ; Dawe, Robert ; Geoghegan, J. A. ; Irvine, A. D. ; Holden, M. T. G. / The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis. In: British Journal of Dermatology. 2018 ; Vol. 179, No. 4. pp. 951-958.
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abstract = "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 (Fus R) being significantly more frequent in AD (P = 0·009). The genetic basis of Fus R also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that Fus R 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.",
author = "Catriona Harkins and McAleer, {M. A.} and D. Bennett and M. McHugh and Fleury, {O. M.} and Pettigrew, {K. A.} and K. Oravcov{\'a} and J. Parkhill and Charlotte Proby and Robert Dawe and Geoghegan, {J. A.} and Irvine, {A. D.} and Holden, {M. T. G.}",
note = "This work was supported by grants from the Wellcome Trust (104241/z/14/z to C.P.H., and 098731/z/11/z to St Andrews University Bioinformatics Unit), and the Chief Scientists Office (SIRN10 to M.T.G.H.).",
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Harkins, C, McAleer, MA, Bennett, D, McHugh, M, Fleury, OM, Pettigrew, KA, Oravcová, K, Parkhill, J, Proby, C, Dawe, R, Geoghegan, JA, Irvine, AD & Holden, MTG 2018, 'The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis', British Journal of Dermatology, vol. 179, no. 4, pp. 951-958. https://doi.org/10.1111/bjd.16722

The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis. / Harkins, Catriona (Lead / Corresponding author); McAleer, M. A.; Bennett, D.; McHugh, M.; Fleury, O. M.; Pettigrew, K. A.; Oravcová, K.; Parkhill, J.; Proby, Charlotte; Dawe, Robert; Geoghegan, J. A.; Irvine, A. D.; Holden, M. T. G.

In: British Journal of Dermatology, Vol. 179, No. 4, 10.2018, p. 951-958.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis

AU - Harkins, Catriona

AU - McAleer, M. A.

AU - Bennett, D.

AU - McHugh, M.

AU - Fleury, O. M.

AU - Pettigrew, K. A.

AU - Oravcová, K.

AU - Parkhill, J.

AU - Proby, Charlotte

AU - Dawe, Robert

AU - Geoghegan, J. A.

AU - Irvine, A. D.

AU - Holden, M. T. G.

N1 - This work was supported by grants from the Wellcome Trust (104241/z/14/z to C.P.H., and 098731/z/11/z to St Andrews University Bioinformatics Unit), and the Chief Scientists Office (SIRN10 to M.T.G.H.).

PY - 2018/10

Y1 - 2018/10

N2 - 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 (Fus R) being significantly more frequent in AD (P = 0·009). The genetic basis of Fus R also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that Fus R 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.

AB - 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 (Fus R) being significantly more frequent in AD (P = 0·009). The genetic basis of Fus R also differentiated the populations, with chromosomal mutations in fusA predominating in AD (P = 0·049). Analysis revealed that Fus R 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.

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U2 - 10.1111/bjd.16722

DO - 10.1111/bjd.16722

M3 - Article

VL - 179

SP - 951

EP - 958

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 4

ER -