Genomic study identifies highly transmissible S. aureus strains in the NICU

Researchers from the Children’s Hospital of Philadelphia (CHOP) have identified strains of Staphylococcus aureus (staph) often transmitted in the neonatal intensive care unit (NICU) and likely to cause severe infection, publishing their findings in Nature Communications.¹

Data has indicated 1 in 4 infections linked to health care in very preterm US infants are caused by staph, defined as bacterium on the skin and in noses that can lead to conditions such as mild skin infections or more severe bloodstream infections. These findings provide a guide for monitoring staph in the NICU and reducing infections in newborns.

“Staph is a critical human pathogen and a major cause of severe infection in our highest-risk infants,” Joseph Zackular, PhD, co-senior author and researcher at CHOP. “In this study, we brought together basic researchers, clinicians, and computational biologists in a highly collaborative effort to address a major challenge in pediatric health.”

Study design and surveillance methods

The study was conducted to provide whole-genome sequencing (WGS) of surveillance isolates of NICU patients, alongside blood cultures and environmental samples.² At the main campus NICU, quarterly methicillin - susceptible S. aureus (MSSA) nares screening was conducted alongside monthly methicillin -resistant S. aureus (MRSA) surveillance.

This surveillance was conducted from October 2021 to July 2022. It was followed by monthly MRSA and MSSA nares surveillance. Quality improvement and infection prevention efforts were consistently performed during this time to reduce rates of S. aureus colonization and infection.

Infants with positive MSSA or MRSA results received a 5-day course of mupirocin starting in July 2022 to complete decolonization. Additionally, daily chlorhexidine bathing was given to infants with central venous catheters.

Environmental sampling and genomic analysis

Lab confirmed bloodstream infections (BSI) and central line-associated bloodstream infections (CLABSI) were defined based on criteria from the Centers for Disease Control National Healthcare Safety Network. When there was no secondary source present, BSI was considered to be primary. BSI in a central in place for more than 2 consecutive days was defined as CLABSI.

All sections of the NICU underwent environmental sampling to determine potential reservoirs of transmission. Whole genome sequencing was performed at the CHOP Microbiome Center, with the Illumina Direct from Colony protocol followed to extract DNA from isolates.

Consistent detection of S. aureus with recurrent positive swabs from NICU patients was reported. S. aureus was isolated in 43 blood cultures from 41 infants across all 7 NICU sections.

Colonization rates and genomic diversity

Investigators highlighted stable MSSA and MRSA colonization rates, including a mean MSSA colonization rate of 25.97% and a mean MRSA colonization rate of 4.98%. Notably, the former significantly exceeded the latter. This pattern was also observed in BSI, with mean rates of 0.37 and 0.06 BSIs per 1000 patient-days, respectively.

There were 1446 high-quality genomes after whole genome sequencing, spanning 449 blood cultures and 15 environmental isolates. Distribution across all major phylogenetic clades was noted, highlighting that the ability to cause infection was not restricted to a specific lineage.

Most genomes from the same patient formed monophyletic groups, but 158 genomes across 36 patients were in separate phylogenetic clades. Investigators identified 24 distinct clades, with a median of 26 genomes per clade. S. aureus transmission on the NICU was indicated in some infants by the phylogenetic pattern and significant rates of colonization.

Investigators also found 490 strains, 360 of which were in the NICU and 130 were not in the NICU. There were also 209 clones, 150 being NICU clones and 59 non-NICU clones. Finally, 69 transmission clusters were identified.

Evidence of predominant NICU acquisition

Of non-cluster strains found outside the NICU, 97% were genomically distinct from NICU strains. According to investigators, this indicates most S. aureus cases were acquired in the NICU. Overall, the data highlighted extensive transmission, persistence, and introduction of both MSSA and MRSA in the NICU.

“Our findings underscore the importance of detecting colonization and transmission for infection prevention and suggest future directions for infection prevention with real-time interventions targeting highly transmissible strains,” wrote investigators.

References

1. Children’s Hospital of Philadelphia, Penn Medicine Researchers identify strategies for preventing the most infectious strains of S. aureus in the NICU. Children’s Hospital of Philadelphia. February 10, 2026. https://www.eurekalert.org/news-releases/1116014
2. She Q, Srinivasan L, Theiller E, et al. Rapid dissemination of Staphylococcus aureus in the neonatal intensive care unit is associated with invasive infection. Nat Commun. 2026. doi:10.1038/s41467-026-69074-z