Markers of epidemiological success of methicillin-resistant Staphylococcus aureus (MRSA) isolates in European populations
Objectives Methicillin-resistant Staphylococcus aureus (MRSA) infections impose a considerable burden on health systems, yet there is remarkable variation in the global incidence and epidemiology of MRSA. The MACOTRA consortium aimed to identify bacterial markers of epidemic success of MRSA isolates in Europe using a representative MRSA collection originating from France, the Netherlands and the United Kingdom.  Methods Operational definitions of success were defined in consortium meetings to compose a balanced strain collection of successful and sporadic MRSA isolates. Isolates were subjected to antimicrobial susceptibility testing and whole genome sequencing, genes were identified and phylogenetic trees constructed. Markers of epidemiological success were identified using genome-based time-scaled haplotypic density (THD) analysis and linear regression. Antimicrobial usage data from ESAC-Net was compared to national MRSA incidence data.  Results Heterogeneity of MRSA isolate collections across countries hampered the use of a unified operational definition of success, so country-specific approaches were used to establish the MACOTRA strain collection. Phenotypic antimicrobial resistance varied within related MRSA populations and across countries. In THD analysis, fluoroquinolone, macrolide and mupirocin resistance were associated with MRSA success, while gentamicin, rifampicin and trimethoprim resistance were associated with sporadicity. Usage of antimicrobials across 29 European countries varied substantially, and beta-lactam, fluoroquinolone, macrolide and aminoglycoside use correlated with MRSA incidence.  Conclusions Our results are the strongest yet to associate MRSA antibiotic resistance profiles and antibiotic usage to incidence of infection and successful clonal spread, which varied by country. Harmonized isolate collection, typing, resistance profiling and alignment with antimicrobial usage over time will aid comparisons and further support country-specific interventions to reduce MRSA burden.