Evaluation of whole blood CD64 for identifying infection in neonates receiving hospital care

Naomi E Spotswood^1,2,3*Peter A Dargaville^4,5Leah Hickey^3,6,7Michelle JL Scoullar^1,3Riya Palchaudhuri^1,8Shuning Zheng¹Timothy Spelman¹Suzanne M Crowe^1,8Hanumesh Kenchapla⁴James G Beeson^1,3David A Anderson^1,9*

• ¹Burnet Institute, Melbourne, Australia
• ²Royal Hobart Hospital, Hobart, Tasmania, Australia
• ³The University of Melbourne, Melbourne, Australia
• ⁴Royal Hobart Hospital, Hobart, Australia
• ⁵Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
• ⁶The Royal Children's Hospital, Melbourne, Australia
• ⁷Murdoch Children's Research Institute, Melbourne, Australia
• ⁸Monash University, Melbourne, Australia
• ⁹Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Infection remains one of the most common causes of death in neonates. However, early detection of neonatal infections to inform treatment decisions remains clinically and technically challenging due to the non-specific nature of symptoms, and the lack of a sufficiently accurate diagnostic test. Neonatal infections and sepsis in adults have been associated with increased CD64 expression on neutrophils. We investigated whole blood CD64 (wbCD64) and neutrophil elastase (NE) in neonates who were evaluated and treated for potential infection and evaluated the potential for these biomarkers as diagnostic tools.Neonates were prospectively recruited from two neonatal units. Whole blood samples were collected at the time of clinical evaluation for potential infection, if antimicrobials were also initiated. Whole blood CD64 and NE, as a marker of the neutrophil count, were measured by enzyme-linked immunosorbent assays (ELISA). Correlations between wbCD64, NE, and standard haematologic indices were evaluated and diagnostic performance of wbCD64 in relation to infections analysed using logistic regression and receiver operating characteristic (ROC) curves.Samples were analysed from a total of 178 episodes of infection evaluation from 163 neonates. Whole blood CD64 and NE had a positive, non-linear correlation. Infection was diagnosed in 45% (80/178) of episodes, and 31% (55/178) had infection that was microbiologically confirmed. There was no association identified between wbCD64 and infections, and wbCD64 had poor diagnostic performance for infection detection. Evaluation of wbCD64 relative to levels of NE did not improve diagnostic performance. WbCD64 levels were significantly higher among a subgroup of neonates aged >48 hours who had microbiologically-confirmed bacterial bloodstream infections (BSI), with optimal sensitivity and specificity for BSI detection 53% and 87% respectively.WbCD64 is generally not significantly associated with infection in neonates, but shows some association with bacterial bloodstream infections. The diagnostic performance of wbCD64, with or without NE, does not afford sufficient diagnostic accuracy to aid antimicrobial therapeutic decisions for neonatal infections.