A ratio of neutrophil CD64 and monocyte CD169 expression demonstrated 100% sensitivity and 96.6% specificity for distinguishing bacterial from viral infections in an initial study of 60 infants.
A blood test comparing the expression of two leukocyte surface markers can accurately differentiate between bacterial and viral infections in febrile infants under three months of age, according to preliminary findings presented at the European Emergency Medicine Congress in Paris.
A fever in infants under three months is considered a medical emergency due to their immature immune systems and the risk that an infection can rapidly become life-threatening. However, identifying which patients require urgent antibiotic therapy remains difficult in emergency settings.
“In very young babies with fever, distinguishing serious bacterial infection from self-limiting viral illness is a major diagnostic dilemma,” says Dr Tommaso Bellini, a paediatric emergency physician at the IRCCS Istituto Giannina Gaslini in Genoa, Italy, in a release. “Our standard biomarkers can help show when there might be a bacterial infection, but they also create ‘false positives’, which drives overtreatment. This can mean unnecessary lumbar punctures, antibiotics, and hospital admissions for infants who turn out to have only a virus.”
Measuring Cell-Surface Expression via Flow Cytometry
The study evaluated 60 infants brought to the paediatric emergency department of IRCCS Istituto Giannina Gaslini who were being managed for fever or other, non-infectious conditions. Researchers collected blood samples from all participants and analyzed them using flow cytometry to quantify the expression of CD64 and CD169.
CD64 is expressed on the surface of neutrophils and increases in response to bacterial infection, while CD169 is expressed on monocytes and rises during viral infection. By pairing these complementary markers into a single ratio, the investigators assessed infection status across patient groups.
The ratio accurately separated infants without infection, who exhibited an average score of 1.10, from those with confirmed viral infections, who had an average score of 0.33, and those with confirmed bacterial infections, who had an average score of 16.22. Overall, the test demonstrated 100% sensitivity for detecting bacterial infection and 96.6% specificity.
“These two marker molecules show opposite signatures – during a viral infection one is high while the other is low, and during a bacterial infection the reverse is true,” says Bellini, in a release. “Combining them into a single ratio separated bacterial from non-bacterial infection with very high accuracy in our initial cohort of 60 babies.”
Translational Horizons and Trial Expansion
While the biomarker strategy performed well in initial testing, its clinical implementation currently faces operational constraints.
“This assessment is currently run on flow cytometry, which needs specialised equipment and trained staff,” says Bellini in a release. “It is not yet a bedside test and not widely available outside of specialist labs. Translating it into a fast, low-cost, point-of-care format is our next research goal.”
The initial single-center investigation is continuing and will expand to include 75 infants. Additionally, the researchers are initiating the DISCERN (Discriminating Infection via Surface CD-marker Expression Ratios iN infancy) study, a prospective, multicenter trial planned to validate diagnostic performance in 300 to 500 infants.
Independent experts noted that improving diagnostic certainty in this population could also support antimicrobial stewardship initiatives.
“This is a small study, but the findings are very positive. If these results can be reinforced in a larger trial, they could mean that we have a much better way of knowing which babies probably have a bacterial infection that needs antibiotics, and which babies probably do not,” says Dr Maša Sorić, head of the emergency department at University Hospital Merkur in Zagreb, Croatia, and member of the European Society for Emergency Medicine abstract selection committee, in a release. “If we can ensure we only use antibiotics when they are needed, we may also reduce the growth of antibiotic resistance, helping to maintain the effectiveness of these vital medicines.”
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