1. In this prospective observational study, infected pediatric intensive care unit (ICU) patients had a significantly higher neutrophil CD 64 (nCD64), C-reactive protein (CRP), and procalcitonin (PCT) than patients without an infection.

2. The nCD64 index was found to have a greater diagnostic value than both CRP and PCT in this study, and the median nCD64 index was found to have a sensitivity of 68.8% and specificity of 90.7% for the presence of infection.

Evidence Rating Level: 2 (Good)

Sepsis is a major cause of death in pediatrics, and while blood cultures are a gold standard to determine bloodstream infection etiology, results may take 2 to 3 days or more, and there are multiple confounding factors including contamination, previous antibiotic use, and sampling time. Thus, blood cultures for detection of pathogens have limited clinical utility. To differentiate between systemic inflammatory response syndrome (SIRS) and an infection as soon as possible, current biomarkers including procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) may be used. However, these biomarkers may also be increased in patients with non-infectious inflammatory responses and conditions. Neutrophil CD64 (nCD64) is a high affinity receptor mainly expressed on the plasma membranes of antigen-presenting cells, and expression of CD64 is increased significantly after activation by pro-inflammatory markers. It is thought that nCD64 may be a sensitive biomarker to distinguish between patients with and without infection. This prospective observational study aimed to evaluate the use of nCD64 index for identification of children in the pediatric ICU (PICU) with and without infection. 201 children were included in the study, admitted in a 3 month study period from April to June 2021. Patients with an infection were classified as having pneumonia, skin and soft-tissue infection, bloodstream infection, digestive stream infection, or central nervous infection. nCD64 was collected from these patients and analyzed with flow cytometry. 201 pediatric patients were included in the study, with 93 (46.3%) children found to have an infection and 108 (53.7%) children that were classified as not infected. With respect to baseline characteristics, the median age was 49 months old, the median length of hospital stay was 15 days, and the median length of PICU stay was 2 days. The infected group was younger, had longer hospital and ICU stays, and were more likely to receive ventilator therapy than the non-infected group (P<.05). Regarding the biomarkers, compared to the noninfected group, the infected group had a significantly greater median nCD64 index (0.18 vs. 0.09, P<.001), median CRP level (5 vs. 0.5 mg/L, P<.001), and median PCT level (0.19 vs. 0.08 ng/mL, P<.001). The median nCD64 index was found to have a sensitivity of 68.8% and specificity of 90.7%, having a greater diagnostic value than both CRP and PCT. In addition, nCD64 was found to be slightly more sensitive and specific than CRP for the identification of infection in postoperative pediatric fevers. Overall, the findings from this study suggest that the nCD64 index was an effective biomarker for infections and had a better diagnostic performance than PCT and CRP for the diagnosis of infection at PICU admission. A major limitation of this study is the small sample size and nature of the study – further high-quality studies would be essential to better understand nCD64 index as a potential infective biomarker. Further research with a larger sample size would be useful to use nCD64 as a potential biomarker to differentiate between viral and bacterial infections, especially given the prevalence of serious viral infections in the pediatric population.

Click to read the study in BMC Pediatrics

Image: PD

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