title: Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16 years: non-linear time series analysis.
abstract: OBJECTIVE
  To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA).
  
  
  METHODS
  Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory.
  
  
  METHODS
  Regional hospital and primary care in a Scottish Health Board.
  
  
  METHODS
  General adult (N=1,051,993) or intensive care (18,235) admissions and primary care registrations (460,000 inhabitants) between January 1997 and December 2012.
  
  
  METHODS
  Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and '4Cs' (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones).
  
  
  METHODS
  Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10,000 inhabitant-days).
  
  
  RESULTS
  67% of all clinical MRSA isolates (10,707/15,947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of '4Cs' and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R(2)=0.63-0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4 days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135-141, and 48-81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes.
  
  
  CONCLUSIONS
  Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts.
authors: Department of Paediatrics, Royal Aberdeen Children's Hospital, Aberdeen, UK.
authors: Timothy
authors: T
authors: Lawes
authors: Medicine Preventive-Infection Control Team, Hospital Vega Baja, Orihuela-Alicante, Spain.
authors: José-María
authors: JM
authors: López-Lozano
authors: Centro Universitario de la Defensa (CUD) de San Javier, Murcia, Murcia, Spain.
authors: César
authors: C
authors: Nebot
authors: Pharmacy Department, Aberdeen Royal Infirmary, Aberdeen, UK.
authors: Gillian
authors: G
authors: Macartney
authors: Pharmacy Department, Aberdeen Royal Infirmary, Aberdeen, UK.
authors: Rashmi
authors: R
authors: Subbarao-Sharma
authors: Medical Microbiology Department, Aberdeen Royal Infirmary, Aberdeen, UK.
authors: Ceri R J
authors: CR
authors: Dare
authors: Scottish MRSA Reference Laboratory, Glasgow, UK.
authors: Giles F S
authors: GF
authors: Edwards
authors: Medical Microbiology Department, Aberdeen Royal Infirmary, Aberdeen, UK.
authors: Ian M
authors: IM
authors: Gould
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015373:Bacterial Typing Techniques; D002511:Cephalosporins / Q000627:therapeutic use; D003428:Cross Infection / Q000517:prevention & control; D004351:Drug Resistance; D063373:Hand Hygiene; D006801:Humans; D017053:Infection Control / Q000379:methods*; D007902:Length of Stay; D018942:Macrolides / Q000627:therapeutic use; D008403:Mass Screening; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D015995:Prevalence; D012189:Retrospective Studies; D012606:Scotland; D013045:Species Specificity; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D018942:Macrolides
keywords: MICROBIOLOGY; STATISTICS & RESEARCH METHODS