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

Objectives: To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Design: Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Setting: Regional hospital and primary care in a Scottish Health Board. Participants: 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. Interventions: Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and '4Cs' (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Outcome measures: 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.