title: Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study.
abstract: BACKGROUND
  Restriction of antibiotic consumption to below predefined total use thresholds might remove the selection pressure that maintains antimicrobial resistance within populations. We assessed the effect of national antibiotic stewardship and infection prevention and control programmes on prevalence density of meticillin-resistant Staphylococcus aureus (MRSA) infections across a region of Scotland.
  
  
  METHODS
  This non-linear time-series analysis and quasi-experimental study explored ecological determinants of MRSA epidemiology among 1,289,929 hospital admissions and 455,508 adults registered in primary care in northeast Scotland. Interventions included antibiotic stewardship to restrict use of so-called 4C (cephalosporins, co-amoxiclav, clindamycin, and fluoroquinolones) and macrolide antibiotics; a hand hygiene campaign; hospital environment inspections; and MRSA admission screening. Total effects were defined as the difference between scenarios with intervention (observed) and without intervention (predicted from time-series models). The primary outcomes were prevalence density of MRSA infections per 1000 occupied bed days (OBDs) in hospitals or per 10,000 inhabitants per day (IDs) in the community.
  
  
  RESULTS
  During antibiotic stewardship, use of 4C and macrolide antibiotics fell by 47% (mean decrease 224 defined daily doses [DDDs] per 1000 OBDs, 95% CI 154-305, p=0·008) in hospitals and 27% (mean decrease 2·52 DDDs per 1000 IDs, 0·65-4·55, p=0·031) in the community. Hospital prevalence densities of MRSA were inversely related to intensified infection prevention and control, but positively associated with MRSA rates in neighbouring hospitals, importation pressures, bed occupancy, and use of fluoroquinolones, co-amoxiclav, and third-generation cephalosporins, or macrolide antibiotics that exceeded hospital-specific thresholds. Community prevalence density was predicted by hospital MRSA rates and above-threshold use of macrolides, fluoroquinolones, and clindamycin. MRSA prevalence density decreased during antibiotic stewardship by 54% (mean reduction 0·60 per 1000 OBDs, 0·01-1·18, p=0·049) in hospital and 37% (mean reduction 0·017 per 10,000 IDs, 0·004-0·029, p=0·012) in the community. Combined with infection prevention and control measures, MRSA prevalence density was reduced by 50% (absolute difference 0·94 cases per 1000 OBDs, 0·27-1·62, p=0·006) in hospitals and 47% (absolute difference 0·033 cases per 10,000 IDs, 0·018-0·048, p<0·0001) in the community.
  
  
  CONCLUSIONS
  Alongside infection control measures, removal of key antibiotic selection pressures during a national antibiotic stewardship intervention predicted large and sustained reductions in hospital-associated and community-associated MRSA.
  
  
  BACKGROUND
  NHS Grampian Research & Development Fund.
authors.affiliation: Department of Paediatrics, Royal Aberdeen Children's Hospital, Aberdeen, UK. Electronic address: t.lawes@nhs.net.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lawes
authors.affiliation: Medicine Preventive-Infection Control Team, Hospital Vega Baja, Orihuela, Spain.
authors.forename: José-María
authors.initials: JM
authors.lastname: Lopez-Lozano
authors.affiliation: Centro Universitario de la Defensa (CUD) de San Javier, Murcia, Spain.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Nebot
authors.affiliation: Pharmacy Department, Aberdeen, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Macartney
authors.affiliation: Pharmacy Department, Aberdeen, UK.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Subbarao-Sharma
authors.affiliation: Medical Microbiology Department, Aberdeen, UK.
authors.forename: Ceri Rj
authors.initials: CR
authors.lastname: Dare
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Wares
authors.affiliation: Medical Microbiology Department, Aberdeen, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Gould
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D003140:Communicable Disease Control / Q000458:organization & administration / Q000706:statistics & numerical data*; D017714:Community-Acquired Infections; D003428:Cross Infection / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology / Q000517:prevention & control; D004363:Drug Utilization / Q000706:statistics & numerical data*; D005260:Female; D063373:Hand Hygiene; D006801:Humans; D018942:Macrolides / Q000627:therapeutic use; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012606:Scotland / Q000453:epidemiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D018942:Macrolides