Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus

M.J. Ellington; S. Reuter; S.R. Harris; M.T.G. Holden; E.J. Cartwright; D. Greaves; S.M. Gerver; R. Hope; N.M. Brown; M.E. Török; J. Parkhill; C.U. Köser; S.J. Peacock

doi:10.1016/j.ijantimicag.2015.01.009

Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus

M.J. Ellington, S. Reuter, S.R. Harris, M.T.G. Holden, E.J. Cartwright, D. Greaves, S.M. Gerver, R. Hope, N.M. Brown, M.E. Török, J. Parkhill, C.U. Köser, S.J. Peacock

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

Abstract

Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n = 23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.

Original language	English
Pages (from-to)	477-484
Journal	International Journal of Antimicrobial Agents
Volume	45
Issue number	5
Early online date	19 Feb 2015
DOIs	https://doi.org/10.1016/j.ijantimicag.2015.01.009
Publication status	Published - May 2015

Keywords

CA-MRSA
Antimicrobial resistance
Surveillance
SCC genomics

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Holden_2015_IJAA_Emergent_CC
© 2015 The Authors. Published by Elsevier B.V. on behalf of International Society of Chemotherapy. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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Ellington, M. J., Reuter, S., Harris, S. R., Holden, M. T. G., Cartwright, E. J., Greaves, D., Gerver, S. M., Hope, R., Brown, N. M., Török, M. E., Parkhill, J., Köser, C. U., & Peacock, S. J. (2015). Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus. International Journal of Antimicrobial Agents, 45(5), 477-484. https://doi.org/10.1016/j.ijantimicag.2015.01.009

@article{84e1bba6ce7e460a8c2897511edf82fe,

title = "Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus",

abstract = "Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n = 23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.",

keywords = "CA-MRSA, Antimicrobial resistance, Surveillance, SCC genomics",

author = "M.J. Ellington and S. Reuter and S.R. Harris and M.T.G. Holden and E.J. Cartwright and D. Greaves and S.M. Gerver and R. Hope and N.M. Brown and M.E. T{\"o}r{\"o}k and J. Parkhill and C.U. K{\"o}ser and S.J. Peacock",

note = "This study was supported by grants from the UKCRC Translational Infection Research Initiative and the Medical Research Council [grant no. G1000803] with contributions to the grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); by the Wellcome Trust [grant no. 098051 awarded to the Wellcome Trust Sanger Institute]; by the Health Protection Agency (to Prof. Peacock); and by the NIHR Cambridge Biomedical Research Centre (to Dr T{\"o}r{\"o}k and Prof. Peacock). EMT is a Clinician Scientist Fellow funded by the Academy of Medical Sciences and the Health Foundation. ",

year = "2015",

month = may,

doi = "10.1016/j.ijantimicag.2015.01.009",

language = "English",

volume = "45",

pages = "477--484",

journal = "International Journal of Antimicrobial Agents",

issn = "0924-8579",

publisher = "Elsevier",

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Ellington, MJ, Reuter, S, Harris, SR, Holden, MTG, Cartwright, EJ, Greaves, D, Gerver, SM, Hope, R, Brown, NM, Török, ME, Parkhill, J, Köser, CU & Peacock, SJ 2015, 'Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus', International Journal of Antimicrobial Agents, vol. 45, no. 5, pp. 477-484. https://doi.org/10.1016/j.ijantimicag.2015.01.009

TY - JOUR

T1 - Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus

AU - Ellington, M.J.

AU - Reuter, S.

AU - Harris, S.R.

AU - Holden, M.T.G.

AU - Cartwright, E.J.

AU - Greaves, D.

AU - Gerver, S.M.

AU - Hope, R.

AU - Brown, N.M.

AU - Török, M.E.

AU - Parkhill, J.

AU - Köser, C.U.

AU - Peacock, S.J.

N1 - This study was supported by grants from the UKCRC Translational Infection Research Initiative and the Medical Research Council [grant no. G1000803] with contributions to the grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Prof. Peacock); by the Wellcome Trust [grant no. 098051 awarded to the Wellcome Trust Sanger Institute]; by the Health Protection Agency (to Prof. Peacock); and by the NIHR Cambridge Biomedical Research Centre (to Dr Török and Prof. Peacock). EMT is a Clinician Scientist Fellow funded by the Academy of Medical Sciences and the Health Foundation.

PY - 2015/5

Y1 - 2015/5

N2 - Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n = 23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.

AB - Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke's Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n = 23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.

KW - CA-MRSA

KW - Antimicrobial resistance

KW - Surveillance

KW - SCC genomics

UR - http://www.sciencedirect.com/science/article/pii/S0924857915000643#appd002

U2 - 10.1016/j.ijantimicag.2015.01.009

DO - 10.1016/j.ijantimicag.2015.01.009

M3 - Article

SN - 0924-8579

VL - 45

SP - 477

EP - 484

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

IS - 5

ER -

Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus

Abstract

Keywords

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