早产儿晚发型细菌性和真菌性败血症的临床早期鉴别

Early clinical identification of late-onset bacterial and fungal sepsis in preterm neonates

目的探讨新生儿ICU(NICU)早产儿晚发型细菌性和真菌性败血症的临床早期特点,以指导临床鉴别诊断和治疗。方法回顾性分析2006年1月—2016年12月上海交通大学医学院附属新华医院NICU收治的晚发型败血症早产儿103例(病例组),根据病原学结果进一步分为细菌组和真菌组,选择与其胎龄、出生体重、性别和出生后发病或观察时间点相似的早产儿206例作为对照组。比较3组的临床症状(包括反应差、体温异常、心动过速、呼吸暂停、青紫、腹胀和喂养不耐受)、并发症发生情况\[包括中枢感染、新生儿坏死性小肠结肠炎(NEC)、支气管肺发育不良(BPD)、早产儿视网膜病变(ROP)、脑室周围和脑室内出血(PIVH)、脑室周围白质软化(PVL)\]和预后不良率(包括死亡或放弃治疗)。收集3组早产儿的血常规检查结果,并采用ROC曲线图分析病例组发病的早期预测因子。结果病例组103例,其中细菌组49例,真菌组54例。细菌组的平均胎龄和出生体重均显著大于真菌组(P值均<0.01),平均胎龄显著大于对照组(P<0.01)。细菌组和真菌组呼吸暂停、青紫、腹胀和喂养不耐受的发生率均显著高于对照组(P值均<0.01),真菌组心动过速、呼吸暂停、青紫的发生率均显著高于细菌组(P值均<0.01)。细菌组和真菌组的NEC发生率均显著高于对照组(P值均<0.01),真菌组的BPD、PIVH和PVL的发生率均显著高于对照组(P值均<0.01)。真菌组的BPD、PIVH、PVL发生率和预后不良率均显著高于细菌组(P值分别<0.01、0.05)。细菌组和真菌组的血红蛋白、血小板计数、血小板比容均显著低于对照组(P值均<0.01);真菌组的红细胞比容显著低于对照组(P<0.05),平均血小板体积显著大于对照组(P<0.01);真菌组的血小板计数、血小板比容均显著低于细菌组(P值均<0.01),平均血小板体积显著大于细菌组(P<0.01)。根据ROC曲线,细菌组未发现诊断准确性较高的指标,真菌组发病早期血小板计数(AUC为0.930,95%CI为0.896~0.964,敏感度为0.74,特异度为0.91,最佳诊断分界点为134.0×109/L)和血小板比容(AUC为0.874,95%CI为0.812~0.936,敏感度为0.77,特异度为0.83,最佳诊断分界点为0.002 5)的诊断准确性均较高。结论早产儿晚发型败血症早期真菌性败血症比细菌性败血症的临床症状更为明显,更容易发生并发症,血小板相关参数的变化也更明显。血小板计数和血小板比容在真菌性败血症发病早期的诊断准确性均较高,可为早期诊断和治疗提供参考依据。

Objective To investigate the early clinical manifestations of late-onset bacterial sepsis versus fungal sepsis in neonate intensive care unit （NICU）. Methods A total of 103 preterm neonates with late-onset sepsis （case group） admitted to the NICU of Xinhua Hospital from January 2006 to December 2016 were enrolled in this retrospective matched case-control study. They were subdivided into bacterial group and fungal group according to the result of etiology. Meanwhile, 206 preterm neonates who had matched gestational age, birth weight, gender, onset time with the babies in the case group were assigned to control group. The clinical symptoms, complications, prognosis and laboratory test results were compared among groups. The early predictive factors of late-onset sepsis in the case group were analyzed by receiver operating characteristic （ROC） curve. Results There were 49 neonates with bacterial sepsis and 54 neonates with fungal sepsis. The average gestational age and birth weight of bacterial group were greater than those of fungal group （both P〈0. 01）, and the average gestational age of neonates with bacterial sepsis was greater than that in the control group （P 〈 0.01）. Poor response, abnormal temperature, tachycardia, apnea, cyanosis, abdominal distension and feeding intolerance were the more common in early stage in the case group than control group. The incidences of apnea, cyanosis, abdominal distension and feeding intolerance in bacterial and fungal groups were significantly higher than those in the control group （all P〈0. 01）. The incidences of tachycardia, apnea, cyanosis in fungal group were significantly higher than those in bacterial group （all P〈0. 01）. There were a variety of common complications, such as central infection, necrotizing enterocolitis of newborn （NEC）, bronchopulmonary dysplasia （BPD）, retinopathy of prematurity （ROP）, periventricular-intraventricular hemorrhage （PIVH） and periventricular leukomalacia （PVL）. The incidence of NEC in bacterial and fungal group were significantly higher than that in the control group （both P〈0. 01 ）. The incidences of BPD, PIVH and PVL in fungal group were significantly higher than those in the control group （all P〈0. 01）. The incidences of BPD, PIVH and PVL and poor prognosis ratio （including death and treatment abandoning） in fungal group were significantly higher than those in bacterial group （P〈0.01 or P 〈0.05）, The hemoglobin, piatelet count and plateletcrit in bacterial and fungal group were significantly lower than those in the control group （all P〈0. 01）. The hematocrit value in fungal group was significantly lower than that in the control group （P〈0. 05）, while the mean platelet volume in fungal group was greater than that in the control group （P 〈 0. 01）. The platelet count and plateletcrit in fungal group were significantly lower than those in bacterial group （both P〈0. 01）, while the mean platelet volume in fungal group was greater than that in the bacterial group （P〈0. 01）. No highly accurate index was found for the diagnosis of bacterial sepsis, while the platelet count （are aunder concentration-time curve[AUC] = 0. 930, 95% CI ： 0. 896-0. 964, sensitivity= 0.74, specificity= 0.91, cut-off： 134.0 × 10^9/L） and plateletcrit （AUC = 0. 874, 95% CI： 0.812 - 0. 936, sensitivity = 0.77, specificity = 0.83, cut-off：0. 002 5） had high accuracy for predicting fungal sepsis. Conclusion Late-onset fungal sepsis is more severe and has more complications and more obvious changes of platelet parameters than late-onset bacteria sepsis in preterm neonates. The platelet count and plateletcrit have high diagnostic accuracy for late-onset fungal sepsis in preterm neonates, and can be used as predictive factors of the disease.