BIOMARKER PROFILES FOR EARLY DIAGNOSIS OF SEPSIS IN NEONATES

用于新生儿脓毒症早期诊断的生物标志物谱

• 批准号: 8356735
• 负责人: MOHAN VENKATESH
• 金额: $ 4.38万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356735
• 关键词: Antibiotic Resistance; Antibiotics; Biological Markers; Birth; Blood; Blood Volume; Blood specimen; Clinical; Clinical Data; Clinical Research; Cohort Studies; Data; Diagnosis; Drops; Early Diagnosis; Early treatment; Enrollment; Evaluation; Funding; Gestational Age; Grant; Infant; Infection; Inflammation Mediators; Inflammatory; Informed Consent; Laboratories; Lead; Life; Measures; Medicine; Methods; Monitor; Morbidity - disease rate; National Center for Research Resources; Neonatal; Outcome; Pattern; Principal Investigator; Recovery; Reporting; Research; Research Infrastructure; Resources; Sample Size; Sampling; Sepsis; Source; United States National Institutes of Health; base; chemokine; clinically significant; cost; cytokine; improved; infant monitoring; inflammatory marker; mortality; neonatal sepsis; neonate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT Background: Neonatal sepsis is a major cause for mortality and morbidity. Diagnosis of sepsis is hampered by 48-72 hr delay in reporting and lack of sensitivity of blood cultures. Antepartum antibiotics and small volumes of blood available for culture further complicate diagnosis. Evaluation of inflammatory biomarkers (e.g. CRP, cytokines and chemokines) is a promising strategy. Correlation of inflammatory biomarker patterns with clinical data may lead us to a rapid and a sensitive method for diagnosis of sepsis and monitor recovery. Hypothesis: The profile of inflammatory mediators measured in neonates will be altered prior to, with the onset and with recovery from sepsis. Methods: This study is an observational cohort study. Infants who weigh =1,500 grams at birth and =32 weeks estimated gestational age admitted to the NICU at TCH are eligible. Infants will be enrolled in the first 10 days of life, after informed consent. Our estimated sample size is 200 infants (600 in total from other centers). Research data that will be collected are blood samples and clinical and laboratory data. An extra drop of blood during routine clinical monitoring of these infants will be used to measure inflammatory biomarker profile by Rules Based Medicine (RBM). No blood draws will be done solely for research purposes. After recruitment of the sample size, 100 infected and 100 non-infected matched controls will be identified. Samples surrounding the infection episode will be analyzed by RBM (7 samples/infant), for a total of 1400 samples. Anticipated results and significance: Clinical and other laboratory data will be correlated to blood inflammatory marker profiles. Analyses of temporal changes in the analyte profile and clinical data in infected and uninfected infants will identify a composite set of markers for rapid identification and monitor recovery from neonatal sepsis. Early diagnosis and therapy of neonatal sepsis will improve neonatal outcomes. Correctly identifying sepsis will avoid excessive antibiotic use and the emergence of antibiotic resistance. I. HYPOTHESES The profile of inflammatory mediators measured in neonates will be altered a) With the onset of sepsis. b) With recovery from sepsis c) Prior to the onset of infection. II. SPECIFIC AIMS 1. To measure inflammatory biomarkers of infection in serial blood samples obtained from 200 eligible infants (=1,500 g at birth and =32 weeks gestational age), 100 with culture proven sepsis and 100 without. 2. Obtain daily clinical and other laboratory data from enrolled infants. 3. Correlate the inflammatory biomarker profile with clinical and other laboratory data to compile baseline values. 4. Compare baseline values between culture-proven infection and those without.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 摘要 背景：新生儿败血症是新生儿死亡和发病的主要原因。脓毒症的诊断因报告延迟48-72小时以及血培养缺乏敏感性而受到阻碍。产前抗生素和少量可供培养的血液使诊断进一步复杂化。评价炎症生物标志物(如：C反应蛋白、细胞因子和趋化因子)是一种很有前途的策略。炎性生物标志物模式与临床数据的相关性可能会引导我们找到一种快速而敏感的方法来诊断脓毒症并监测康复情况。 假设：新生儿的炎性介质在败血症发生前、发病后和痊愈后都会发生改变。 方法：本研究为观察性队列研究。出生时体重=1,500克，估计胎龄=32周的婴儿进入TCH的NICU是符合条件的。在知情同意后，婴儿将在出生后的头10天进行登记。我们估计样本大小为200名婴儿(来自其他中心的样本总数为600名)。将收集的研究数据包括血液样本以及临床和实验室数据。在这些婴儿的常规临床监测中，额外的一滴血将被用于通过基于规则的医学(RBM)来测量炎症生物标记物的概况。不会只为研究目的而抽血。在招募样本大小后，将确定100名感染和100名未感染的匹配对照。感染事件周围的样本将用RBM(7个样本/婴儿)进行分析，总共1400个样本。 预期结果和意义：临床和其他实验室数据将与血液炎症标志物图谱相关。对感染和未感染婴儿的分析物图谱和临床数据的时间变化的分析将确定一组复合的标志物，用于快速识别和监测新生儿败血症的恢复情况。新生儿败血症的早期诊断和治疗将改善新生儿预后。正确识别脓毒症将避免过度使用抗生素和出现抗生素耐药性。 一、假设 新生儿体内测量的炎性介质的分布将发生改变。 A)出现败血症。 B)败血症康复 C)在感染开始之前。 二、具体目标 1.从200名符合条件的婴儿(出生时=1500克，胎龄=32周)，100名培养证实为脓毒症的婴儿和100名非脓毒症婴儿的连续血液样本中检测感染的炎性生物标志物。 2.获取登记婴儿的每日临床和其他实验室数据。 3.将炎性生物标志物概况与临床和其他实验室数据相关联，以编制基线值。 4.比较培养证实的感染和未感染患者的基线值。