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.
authors.affiliation: Public Health England, Microbiology Services Division, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. Electronic address: matthew.ellington@phe.gov.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellington
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Matthew T G
authors.initials: MT
authors.lastname: Holden
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Cartwright
authors.affiliation: Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Greaves
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Gerver
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Russell
authors.initials: R
authors.lastname: Hope
authors.affiliation: Public Health England, Microbiology Services Division, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Brown
authors.affiliation: Public Health England, Microbiology Services Division, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: M Estee
authors.initials: ME
authors.lastname: Török
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK.
authors.forename: Claudio U
authors.initials: CU
authors.lastname: Köser
authors.affiliation: Public Health England, Microbiology Services Division, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QW, UK; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D004363:Drug Utilization / Q000639:trends; D019143:Evolution, Molecular; D005260:Female; D005672:Fusidic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005798:Genes, Bacterial; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D008875:Middle Aged; D015995:Prevalence; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005672:Fusidic Acid
keywords: Antimicrobial resistance; CA-MRSA; SCC genomics; Surveillance