Transmission ofStaphylococcus aureusin the neonatal intensive care unit predicts invasive infection

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Abstract

Background

Staphylococcus aureusis 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 byS. aureuspresents a significant risk for subsequent infection of the colonized infant and for patient-to-patient transmission. Transmission of more virulentS. aureusstrains in the NICU could increase infection risk in this vulnerable population.

Methods

We performed a three-year, unit-wide screening forS. aureusin the Children’s 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 ofS. aureusin the NICU setting.

Findings

Our analyses revealed 490 unique strains with multiple, highly related, clones among NICUS. aureusgenomes. We identified sixty-nine transmission clusters, of which 87% (60/69) were methicillin susceptibleS. 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 revealedS. aureuson 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.

Interpretations

Genomic temporal-spatial epidemiologic analyses revealed high levels ofS. aureustransmission 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 preventS. aureusinfections in the NICU setting.

Funding

This work was supported by the Center for Microbial Medicine, Microbial Archive and Cryocollection and the Research Institute (CLABSI Innovation and OMICS Initiative) at CHOP.

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