A routine laboratory clock may hold the key to reducing unnecessary antibiotic exposure among newborns in intensive care. A new study in the Journal of Perinatology revisits how long clinicians should wait for a blood culture to become positive before deciding that a premature or critically ill infant is unlikely to have a bloodstream infection. The question is deceptively simple, but in neonatal intensive care units, where infection can progress rapidly and symptoms are often subtle, every hour brings a difficult balance between protecting vulnerable infants and avoiding treatment they may not need.
The study, led by R.J. Graf, A. Edwards, M.A. Crowley and colleagues, focuses on “time to blood culture positivity,” the interval between collecting a blood sample and detecting microbial growth in the laboratory. Blood cultures remain a central tool for diagnosing sepsis, including late-onset sepsis in newborns. When bacteria or fungi are present, they may multiply in the culture bottle and trigger an automated signal. If no growth is detected after a defined period, clinicians must decide whether antibiotics can safely be stopped, even though a negative result cannot provide absolute certainty.
That decision is especially consequential in the NICU. Newborns, particularly those born very prematurely or with very low birth weight, have immature immune systems and limited physiological reserves. Infection may present with nonspecific changes in breathing, temperature, feeding, heart rate or blood pressure. Because the consequences of missing sepsis can be catastrophic, clinicians often begin broad-spectrum antibiotics while awaiting culture results. Yet many infants who receive this emergency treatment ultimately do not have a confirmed infection.
The resulting exposure is not harmless. Antibiotics can disrupt the developing intestinal microbiome, the complex community of microorganisms that influences digestion, immune development and resistance to invading pathogens. In premature infants, alterations in this ecosystem have been associated with concerns including intestinal inflammation and vulnerability to antimicrobial-resistant organisms. Prolonged or repeated treatment can also expose infants to medication toxicity and contribute to the wider public-health problem of antibiotic resistance. The clinical challenge is therefore not simply to use antibiotics quickly, but to use them for the shortest safe duration.
A blood culture’s time to positivity is influenced by several technical and biological factors. The number of organisms in the original sample, the volume of blood collected, the type of pathogen and whether antibiotics were given before the sample was obtained can all affect detection. In neonates, the small amount of blood that can safely be drawn creates an additional limitation. A culture containing only a tiny number of microorganisms may take longer to signal than one with a larger initial burden, while prior antimicrobial exposure may suppress growth altogether.
The study’s focus reflects a broader effort to make antibiotic decisions more precise rather than relying on a fixed waiting period for every infant. If the great majority of clinically meaningful bloodstream infections become detectable within a defined window, then continuing antibiotics beyond that point may provide little additional protection for infants who remain stable and whose cultures show no growth. Conversely, if certain organisms or clinical situations regularly require more time, an overly aggressive stopping rule could create unacceptable risk. The value of a time-based approach depends on how accurately it distinguishes these different scenarios.
This is why culture timing cannot be interpreted in isolation. Neonatologists must combine laboratory results with the infant’s clinical condition, the quality of the blood sample, inflammatory markers, the likelihood of infection before testing and the presence of other possible sources of illness. A negative culture does not automatically exclude infection, particularly when the sample volume is inadequate or antibiotics were administered first. The study’s central question is therefore not whether a clock can replace clinical judgment, but whether better evidence about that clock can support safer, more consistent decisions.
The work arrives at a moment when hospitals are increasingly adopting antimicrobial stewardship programs designed specifically for newborn care. These programs seek to reduce unnecessary antibiotic starts and shorten treatment courses without increasing missed infections or complications. In practice, the findings from research on culture positivity could help NICUs develop protocols that define when antibiotics should be reassessed, what additional evidence should be considered and which infants require prolonged observation. Such protocols could also reduce variation between clinicians and institutions, where local habits sometimes determine treatment duration as much as microbiological evidence.
For families, the issue is often experienced as a confusing trade-off: antibiotics may be started urgently, but stopping them can feel risky when a newborn remains medically fragile. Clearer data about when cultures become positive could make those conversations more transparent. It could also encourage hospitals to improve the fundamentals of culture collection, including obtaining an adequate blood volume before treatment whenever clinically possible, because laboratory timing is meaningful only when the initial sample is capable of detecting infection.
By revisiting the timing of blood culture positivity, Graf, Edwards, Crowley and their colleagues place a familiar diagnostic test at the center of a pressing neonatal-care question. The ultimate goal is not simply fewer antibiotic doses, but a more accurate separation between infants who need immediate and sustained treatment and those for whom early therapy can be safely discontinued. In the NICU, where both infection and over-treatment carry real dangers, refining that distinction could turn a laboratory result into a powerful tool for protecting newborn health.
Subject of Research: Time to blood culture positivity and reducing antibiotic exposure in the neonatal intensive care unit (NICU)
Article Title: Revisiting time to blood culture positivity: can we decrease antibiotic exposure in the NICU?
Article References: Graf, R.J., Edwards, A., Crowley, M.A. et al. “Revisiting time to blood culture positivity: can we decrease antibiotic exposure in the NICU?” Journal of Perinatology (2026). https://doi.org/10.1038/s41372-026-02838-z
Image Credits: AI Generated
DOI: 10.1038/s41372-026-02838-z
Keywords: neonatal intensive care, blood culture, time to positivity, neonatal sepsis, antibiotic stewardship, premature infants, antimicrobial exposure, microbiology
Tags: balancing infection risk and antibiotic use in NICUblood culture positivity in neonatal sepsisclinical decision-making in neonatal infection managementearly detection of neonatal sepsisimpact of blood culture timing on antibiotic durationlate-onset neonatal sepsis diagnosisNeonatal blood culture timingneonatal bloodstream infection detectionneonatal intensive care unit infection managementNICU antibiotic stewardshipoptimal blood culture incubation periodreducing unnecessary antibiotic exposure in newborns
