Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs

Sian-Marie Frosini, Ross Bond, Merja Hilma Johanna Rantala, Thomas Sven Christer Grönthal, Shelley Rankin, K O'Shea, Dorina Timofte, Vanessa Schmidt, Jodi Lindsay, Anette Loeffler

Research output: Contribution to journalArticleScientificpeer-review

Abstract

BackgroundConcern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC 64mg/L (n=27) fusA and fusE were amplified and sequenced.ResultsFA resistance determinants (fusA mutations n=24, fusB n=2, fusC n=36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (1mg/L), although 4 SP isolates had MICs of 0.06mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n=2) and smr (n=5), which were found in SEUK SA, and SP from NUK and U.S.A.ConclusionsIncreased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy.

Original languageEnglish
Article number81
JournalBMC Microbiology
Volume19
Number of pages10
ISSN1471-2180
DOIs
Publication statusPublished - 25 Apr 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • ANTIMICROBIAL THERAPY
  • AUREUS
  • BIOCIDE TOLERANCE
  • CASSETTE CHROMOSOME MEC
  • Canine
  • Chlorhexidine
  • Fusidic acid
  • IN-VITRO
  • METHICILLIN-RESISTANT
  • METICILLIN-RESISTANT
  • POLYMERASE-CHAIN-REACTION
  • QAC GENES
  • Resistance
  • Staphylococci
  • TOPICAL THERAPY
  • Veterinary
  • 1183 Plant biology, microbiology, virology
  • 413 Veterinary science

Cite this

Frosini, Sian-Marie ; Bond, Ross ; Rantala, Merja Hilma Johanna ; Grönthal, Thomas Sven Christer ; Rankin, Shelley ; O'Shea, K ; Timofte, Dorina ; Schmidt, Vanessa ; Lindsay, Jodi ; Loeffler, Anette. / Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs. In: BMC Microbiology. 2019 ; Vol. 19.
@article{66f8fec374e6492a9e5bfd62b27c1642,
title = "Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs",
abstract = "BackgroundConcern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC 64mg/L (n=27) fusA and fusE were amplified and sequenced.ResultsFA resistance determinants (fusA mutations n=24, fusB n=2, fusC n=36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (1mg/L), although 4 SP isolates had MICs of 0.06mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n=2) and smr (n=5), which were found in SEUK SA, and SP from NUK and U.S.A.ConclusionsIncreased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy.",
keywords = "ANTIMICROBIAL THERAPY, AUREUS, BIOCIDE TOLERANCE, CASSETTE CHROMOSOME MEC, Canine, Chlorhexidine, Fusidic acid, IN-VITRO, METHICILLIN-RESISTANT, METICILLIN-RESISTANT, POLYMERASE-CHAIN-REACTION, QAC GENES, Resistance, Staphylococci, TOPICAL THERAPY, Veterinary, 1183 Plant biology, microbiology, virology, 413 Veterinary science",
author = "Sian-Marie Frosini and Ross Bond and Rantala, {Merja Hilma Johanna} and Gr{\"o}nthal, {Thomas Sven Christer} and Shelley Rankin and K O'Shea and Dorina Timofte and Vanessa Schmidt and Jodi Lindsay and Anette Loeffler",
year = "2019",
month = "4",
day = "25",
doi = "10.1186/s12866-019-1449-z",
language = "English",
volume = "19",
journal = "BMC Microbiology",
issn = "1471-2180",
publisher = "BMC",

}

Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs. / Frosini, Sian-Marie; Bond, Ross; Rantala, Merja Hilma Johanna; Grönthal, Thomas Sven Christer; Rankin, Shelley; O'Shea, K; Timofte, Dorina; Schmidt, Vanessa; Lindsay, Jodi; Loeffler, Anette.

In: BMC Microbiology, Vol. 19, 81, 25.04.2019.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs

AU - Frosini, Sian-Marie

AU - Bond, Ross

AU - Rantala, Merja Hilma Johanna

AU - Grönthal, Thomas Sven Christer

AU - Rankin, Shelley

AU - O'Shea, K

AU - Timofte, Dorina

AU - Schmidt, Vanessa

AU - Lindsay, Jodi

AU - Loeffler, Anette

PY - 2019/4/25

Y1 - 2019/4/25

N2 - BackgroundConcern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC 64mg/L (n=27) fusA and fusE were amplified and sequenced.ResultsFA resistance determinants (fusA mutations n=24, fusB n=2, fusC n=36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (1mg/L), although 4 SP isolates had MICs of 0.06mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n=2) and smr (n=5), which were found in SEUK SA, and SP from NUK and U.S.A.ConclusionsIncreased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy.

AB - BackgroundConcern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC 64mg/L (n=27) fusA and fusE were amplified and sequenced.ResultsFA resistance determinants (fusA mutations n=24, fusB n=2, fusC n=36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (1mg/L), although 4 SP isolates had MICs of 0.06mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n=2) and smr (n=5), which were found in SEUK SA, and SP from NUK and U.S.A.ConclusionsIncreased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy.

KW - ANTIMICROBIAL THERAPY

KW - AUREUS

KW - BIOCIDE TOLERANCE

KW - CASSETTE CHROMOSOME MEC

KW - Canine

KW - Chlorhexidine

KW - Fusidic acid

KW - IN-VITRO

KW - METHICILLIN-RESISTANT

KW - METICILLIN-RESISTANT

KW - POLYMERASE-CHAIN-REACTION

KW - QAC GENES

KW - Resistance

KW - Staphylococci

KW - TOPICAL THERAPY

KW - Veterinary

KW - 1183 Plant biology, microbiology, virology

KW - 413 Veterinary science

U2 - 10.1186/s12866-019-1449-z

DO - 10.1186/s12866-019-1449-z

M3 - Article

VL - 19

JO - BMC Microbiology

JF - BMC Microbiology

SN - 1471-2180

M1 - 81

ER -