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

C P Harkins; M A McAleer; D Bennett; M McHugh; O M Fleury; K A Pettigrew; K Oravcová; J Parkhill; C M Proby; R S Dawe; J A Geoghegan; A D Irvine; M T G Holden

doi:10.1111/bjd.16722

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

C P Harkins, M A McAleer, D Bennett, M McHugh, O M Fleury, K A Pettigrew, K Oravcová, J Parkhill, C M Proby, R S Dawe, J A Geoghegan, A D Irvine, M T G Holden

Microbiology and Infection

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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 (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.

Original language	English
Pages (from-to)	951-958
Number of pages	8
Journal	British Journal of Dermatology
Volume	179
Issue number	4
DOIs	https://doi.org/10.1111/bjd.16722
Publication status	Published - Oct 2018

Bibliographical note

Keywords

Administration, Cutaneous
Anti-Infective Agents, Local/administration & dosage
Carrier State/diagnosis
Case-Control Studies
Child
Child, Preschool
Dermatitis, Atopic/diagnosis
Drug Resistance, Bacterial/drug effects
Female
Healthy Volunteers
Humans
Infant
Infant, Newborn
Male
Microbial Sensitivity Tests
Mutation
Nasal Mucosa/microbiology
Peptide Elongation Factor G/genetics
Severity of Illness Index
Skin/microbiology
Staphylococcal Skin Infections/diagnosis
Staphylococcus aureus/isolation & purification

Access to Document

10.1111/bjd.16722

Cite this

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. (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

@article{395cdfd8a4ff403baf121c7591c56321,

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

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 (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.",

keywords = "Administration, Cutaneous, Anti-Infective Agents, Local/administration & dosage, Carrier State/diagnosis, Case-Control Studies, Child, Child, Preschool, Dermatitis, Atopic/diagnosis, Drug Resistance, Bacterial/drug effects, Female, Healthy Volunteers, Humans, Infant, Infant, Newborn, Male, Microbial Sensitivity Tests, Mutation, Nasal Mucosa/microbiology, Peptide Elongation Factor G/genetics, Severity of Illness Index, Skin/microbiology, Staphylococcal Skin Infections/diagnosis, Staphylococcus aureus/isolation & purification",

author = "Harkins, {C P} 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 Proby, {C M} and Dawe, {R S} and Geoghegan, {J A} and Irvine, {A D} and Holden, {M T G}",

note = "{\textcopyright} 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.",

year = "2018",

month = oct,

doi = "10.1111/bjd.16722",

language = "English",

volume = "179",

pages = "951--958",

journal = "British Journal of Dermatology",

issn = "0007-0963",

publisher = "Wiley",

number = "4",

}

Harkins, CP, McAleer, MA, Bennett, D, McHugh, M, Fleury, OM, Pettigrew, KA, Oravcová, K, Parkhill, J, Proby, CM, Dawe, RS, 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

TY - JOUR

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

AU - Harkins, C P

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, C M

AU - Dawe, R S

AU - Geoghegan, J A

AU - Irvine, A D

AU - Holden, M T G

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 (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.

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 (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.

KW - Administration, Cutaneous

KW - Anti-Infective Agents, Local/administration & dosage

KW - Carrier State/diagnosis

KW - Case-Control Studies

KW - Child

KW - Child, Preschool

KW - Dermatitis, Atopic/diagnosis

KW - Drug Resistance, Bacterial/drug effects

KW - Female

KW - Healthy Volunteers

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Microbial Sensitivity Tests

KW - Mutation

KW - Nasal Mucosa/microbiology

KW - Peptide Elongation Factor G/genetics

KW - Severity of Illness Index

KW - Skin/microbiology

KW - Staphylococcal Skin Infections/diagnosis

KW - Staphylococcus aureus/isolation & purification

U2 - 10.1111/bjd.16722

DO - 10.1111/bjd.16722

M3 - Article

C2 - 29729180

SN - 0007-0963

VL - 179

SP - 951

EP - 958

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this