Abstract
This study aims to evaluate the diagnostic utilities of four leukocyte surface antigens—two lymphocyte antigens (CD25 and CD45RO) and two neutrophil antigens (CD11b and CD64)—for identification of late-onset nosocomial bacterial infection in preterm, very low birthweight infants, and to define the optimal cutoff value for each marker so that it may act as a reference with which future studies can be compared. Very low birthweight infants in whom infection was suspected when they were >72 h of age were eligible for the study. A full sepsis screen was performed in each episode. IL-6, C-reactive protein, and leukocyte surface antigens (CD25, CD45RO, CD11b, and CD64) were measured at 0 (at the time of sepsis evaluation), 24, and 48 h by standard biochemical methods and quantitative flow cytometric analysis. The diagnostic utilities including sensitivity, specificity, and positive and negative predictive values of each marker and combination of markers for predicting late-onset neonatal infection were determined. One hundred twenty-seven episodes of suspected clinical sepsis were investigated in 80 infants. Thirty-seven episodes were proven infection. The calculated optimal cutoff values for CD25, CD45RO, CD11b, and CD64 were 3,100, 2,900, 10,450, and 4,000 phycoerythrin-molecules bound per cell, respectively. An interim analysis of data after 68 episodes suggested that CD25 and CD45RO were poor predictors of neonatal infection with sensitivity or specificity <75% during a single measurement. Thus, these two markers were excluded from further investigation. In the final analysis, CD64 has the highest sensitivity (95–97%) and negative predictive value (97–99%) at 0 and 24 h after the onset. The addition of IL-6 or C-reactive protein (0 h) to CD64 (24 h) further enhanced the sensitivity and negative predictive value to 100%, and has the specificity and positive predictive value exceeding 88% and 80%, respectively. Neutrophil CD64 expression is a very sensitive marker for diagnosing late-onset nosocomial infection in very low birthweight infants. If further validated, the use of CD64 as an infection marker should allow early discontinuation of antibiotic treatment at 24 h without waiting for the definitive microbiologic culture results. The quantitative flow cytometric analysis applied in this study could be developed into a routine clinical test with high comparability and reproducibility across different laboratories.
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Abbreviations
- CRP:
-
C-reactive protein
- CSF:
-
cerebrospinal fluid
- FcγRI:
-
Fcγ-receptor I
- MFI:
-
mean fluorescence intensity
- NEC:
-
necrotizing enterocolitis
- NPV:
-
negative predictive value
- perCP:
-
peridinin chlorophyll protein
- PE:
-
phycoerythrin
- PPV:
-
positive predictive value
- ROC:
-
receiver operating characteristics
- TNF-α:
-
tumor necrosis factor-α
- VLBW:
-
very low birthweight
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Acknowledgements
The authors thank Melinda Leong, Becton Dickinson Immunocytometry Systems, Singapore, for her technical advice on this project.
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Ng, P., Li, K., Wong, R. et al. Neutrophil CD64 Expression: A Sensitive Diagnostic Marker for Late-Onset Nosocomial Infection in Very Low Birthweight Infants. Pediatr Res 51, 296–303 (2002). https://doi.org/10.1203/00006450-200203000-00006
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DOI: https://doi.org/10.1203/00006450-200203000-00006
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