Ng Pak C, Li Karen, Wong Raymond P O, Chui Kit M, Wong Eric, Fok Tai F
Department of Pediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, PR China.
Pediatr Res. 2002 Mar;51(3):296-303. doi: 10.1203/00006450-200203000-00006.
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.
本研究旨在评估四种白细胞表面抗原——两种淋巴细胞抗原（CD25和CD45RO）以及两种中性粒细胞抗原（CD11b和CD64）在识别早产极低出生体重儿晚发性医院获得性细菌感染中的诊断效用，并确定每种标志物的最佳临界值，以便作为未来研究可与之比较的参考标准。年龄大于72小时且怀疑感染的极低出生体重儿符合本研究条件。每次发作时均进行全面的败血症筛查。在0小时（败血症评估时）、24小时和48小时，通过标准生化方法和定量流式细胞术分析检测白细胞介素-6、C反应蛋白和白细胞表面抗原（CD25、CD45RO、CD11b和CD64）。确定了每种标志物以及标志物组合预测晚发性新生儿感染的诊断效用，包括敏感性、特异性、阳性和阴性预测值。对80例婴儿的127次疑似临床败血症发作进行了调查。37次发作被证实为感染。计算得出CD25、CD45RO、CD11b和CD64的最佳临界值分别为每细胞结合3100、2900、10450和4000个藻红蛋白分子。对68次发作后的数据分析进行的中期分析表明，在单次测量时，CD25和CD45RO对新生儿感染的预测能力较差，敏感性或特异性<75%。因此，将这两种标志物排除在进一步研究之外。在最终分析中，CD64在发病后0小时和24小时具有最高的敏感性（95 - 97%）和阴性预测值（97 - 99%）。将白细胞介素-6或C反应蛋白（0小时）与CD64（24小时）联合使用可进一步将敏感性和阴性预测值提高到100%，特异性和阳性预测值分别超过88%和80%。中性粒细胞CD64表达是诊断极低出生体重儿晚发性医院获得性感染的非常敏感的标志物。如果进一步验证，将CD64用作感染标志物应能在24小时时提前停用抗生素治疗，而无需等待明确的微生物培养结果。本研究中应用的定量流式细胞术分析可发展成为一种常规临床检测方法，在不同实验室之间具有高度的可比性和可重复性。
