Sepsis, or bacterial infection of the bloodstream, is a grave, hard-to-diagnose threat in premature newborns in the NICU. Even when it's detected and treated with antibiotics, its inflammatory effects can harm fragile babies' development. Now, researchers at Boston Children 's Hospital have modeled the effects of sepsis on the unique newborn immune system, using mice. They and others have begun using the model to identify diagnostic markers and better treatments.
The new model is described September 6 in the online open-access journal PLOS ONE (available after publication at: http://dx.plos.org/10.1371/journal.pone.0043897).
Premature infants typically are kept alive with catheters and intravenous lines that are vital for their care, but that also carry a risk of bloodstream infection, most commonly from the bacterium Staphylococcus epidermidis. Preventive measures can now avoid many of these infections, but those that slip through can be hard to spot and treat.
"When infection occurs, it's hard to detect in newborns, who can't speak and, due to their unique immune systems, tend not to have fevers or show clinical signs," explains Ofer Levy, MD, PhD, of the Division of Infectious Diseases at Boston Children's and senior author on the paper. "There may be irregular breathing or increased heart rate, or the baby may be acting a little 'off,' but these signs are pretty nonspecific. There's a tremendous need for better diagnostics in this field."
Mouse models of intravenous infections in newborns have been lacking, due to the technical challenge of working with tiny newborn mice. With great manual dexterity, Kenny Kronforst, MD, MPH, a clinical Newborn Medicine fellow working in Levy's lab and first author on the paper, was able to inject live S. epidermidis into the tiny animals' jugular veins, simulating what happens when an IV or catheter infection occurs in an hours-old preemie in the NICU.
The findings surprised the team-and gave hope.
"Newborns have traditionally been considered immunologically immature and distinct from adults in their ability to fight off infection," says Kronforst, now an attending physician in neonatology at Lurie Children's Hospital of Chicago. "Through our model, we have shown that there is a robust inflammatory response to bacterial challenge even at the earliest hours of life. Additionally, we were able to reproduce many clinical features of sepsis that we see in human infants. Because of these features, our model is ideal for exploring novel diagnostic and therapeutic possibilities-something we're extremely excited about."