Transmission of Staphylococcus aureus in the neonatal intensive care unit predicts invasive infection

BackgroundStaphylococcus aureus is a leading cause of healthcare-associated infection and is one of the most common pathogens causing serious invasive infection in the neonatal intensive care unit (NICU). Asymptomatic colonization by S. aureus presents a significant risk for subsequent infection of the colonized infant and for patient-to-patient transmission. Transmission of more virulent S. aureus strains in the NICU could increase infection risk in this vulnerable population. MethodsWe performed a three-year, unit-wide screening for S. aureus in the Childrens Hospital of Philadelphia (CHOP) NICU, with whole genome sequencing (WGS) of 1,670 isolates from patient colonization surveillance, blood cultures from both NICU and non-NICU patients, and environmental surfaces. We used comparative genomic epidemiological approaches to investigate the transmission dynamics of S. aureus in the NICU setting. FindingsOur analyses revealed 490 unique strains with multiple, highly related, clones among NICU S. aureus genomes. We identified sixty-nine transmission clusters, of which 87% (60/69) were methicillin susceptible S. aureus (MSSA), and 28% (19/69) included isolates from both colonizing sites and bacteremia. The largest invasive cluster persisted over 2 years, involved 30 infants, and caused 4 cases of bacteremia. Spatial and temporal epidemiological links were found in 88% of clusters, and suggest that shared spaces served as the predominant means of transmission in the NICU setting. NICU environmental surveillance revealed S. aureus on surfaces; 3 of these isolates were also identified in colonizing and invasive clusters, suggesting potential environmental reservoirs. Remarkably, transmission clusters with both colonizing and invasive isolates were associated with higher rates of transmission, suggesting that specific transmission clusters pose a significantly higher risk for invasive infections in the NICU. InterpretationsGenomic temporal-spatial epidemiologic analyses revealed high levels of S. aureus transmission in the NICU with multiple transmission clusters that persisted over long periods of time. Our findings demonstrate a strong association amongst colonization, transmission, and the development of invasive infections, underscoring the importance of targeted measures to prevent S. aureus infections in the NICU setting. FundingThis work was supported by the Center for Microbial Medicine, Microbial Archive and Cryocollection and the Research Institute (CLABSI Innovation and OMICS Initiative) at CHOP.