Prospective genomic surveillance reveals cryptic MRSA outbreaks with local to international origins among NICU patients

Abstract MRSA infections cause significant morbidity and mortality in neonates. Clinical testing and routine surveillance screening identified an increase in neonates with MRSA colonization and infection which triggered prospective genomic surveillance. Here we show the complex transmission dynamics of MRSA in a NICU setting. Analyses revealed concurrent transmission chains affecting 16 of 22 MRSA-colonized patients (68%), and 3.1% of all NICU patients (n=517). Prematurity and longer lengths of stay increased risks for colonization. Intervals of up to 7 months occurred among some cluster-related isolates. 3 of 22 MRSA-colonized patients developed invasive infections with the colonizing strain. Comparisons with 21,521 isolates in the NCBI Pathogen Detection Resource revealed NICU strains to be distinct from MRSA seen locally and internationally. Integration of international strain datasets in analyses increased the resolution of strain clusters and helped rule-out suspected transmission events. Analyses also identified sequence type 1535 isolates, emergent in the Middle East, carrying a unique SCCmec with fusC and aac(6’)-Ie/aph(2’’)-1a that provided a multi-drug resistant phenotype. NICU genomic surveillance identified cryptic MRSA colonization events, including NICU-endemic strains not linked with local hospital or international clusters, and has rich potential to guide improvements in infection prevention for this vulnerable patient population.