A Path to Prevention: Precision Tracking of Staph in NICUs Reveals Hidden Transmission Risks

A study led by researchers at Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania may reshape how clinicians understand and prevent Staphylococcus aureus infections in neonatal intensive care units (NICUs). Their findings were published in Nature Communications.

By using whole-genome sequencing and precision surveillance over a few years, investigators mapped how specific staph strains spread, persist, and cause disease in high-risk infants—offering a new roadmap for infection control.

Staph can lead to severe infections in vulnerable populations such as preterm infants. The study found that one in four healthcare-associated infections in very preterm US infants is caused by staph, underscoring the urgency of improved prevention strategies.

A key gap the researchers aimed to address was understanding where infections originate. “We really wanted to know how many of the patients who were being colonized or infected with strains of staph aureus were being had that happen in the NICU,” said Paul J. Planet, MD, PhD, an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia and co-director of the Center for Microbial Medicine at CHOP. While newborns naturally acquire bacteria from their parents and environment, the team suspected that certain strains adapted to the NICU setting might pose greater risks due to their ability to spread and persist.

Their findings confirmed that shared spaces and physical proximity are major drivers of transmission. Environmental sampling revealed that identical strains found in patients could also be detected on surfaces such as drying shelves, equipment, and medical carts—highlighting the NICU as a complex microbial ecosystem.

“It's not only about the patient. What we found in this study and other studies [is that] it's the ecosystem around them,” said Ahmed M. Moustafa, BPharm, PhD, a researcher in the Division of Gastroenterology, Hepatology and Nutrition and co-director of the Center for Microbial Medicine at CHOP and the sequencing core director of the CHOP Microbiome Center, emphasizing that transmission involves both people and their surroundings.

Perhaps most striking, the study challenges the long-standing focus on methicillin-resistant Staphylococcus aureus (MRSA) as the primary threat. Instead, methicillin-susceptible strains (MSSA) were responsible for more colonization and invasive disease.

“People start to kind of almost forget that MSSA is still a pathogen and can still be just as damaging and infectious as MRSA,” Planet said. The ability to distinguish high-risk strains within MSSA represents a major shift toward more precise infection control.

The research also highlights the importance of continuous surveillance rather than reactive measures. “If you only screen during outbreaks, you’re already late,” said Moustafa. Advances in genomic sequencing and new diagnostic tools now make it possible to track transmission in near real time, identifying whether the same strain is spreading between patients or lingering in the environment.

NICUs routinely use strain-level monitoring to guide targeted interventions—such as focused cleaning, patient decolonization, or enhanced precautions for specific high-risk strains. Rather than attempting to eliminate all bacteria, the goal is precision: identifying and removing the strains most likely to cause harm. They want to scale this up to be able to look for multiple clones.

“Success for us means fewer persistent transmission clusters, right? Like we know now that some of these clusters are resistant in the environment for over 3 years, so having fewer of these clusters, and also earlier identification of new clusters with these high risk that we call high risk clones, would ultimately result in fewer bloodstream infections and invasive infections in general, which I think would be it's the goal of our program,” said Moustafa.

“I think it is really, really powerful with knowing which clones are there and how well they survive.We now can evaluate how good our strategies are for getting rid of those clones. In the past, there was no way to measure that,” Planet said.

Reference
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 17, 2550 (2026). https://doi.org/10.1038/s41467-026-69074-z