Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger
Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger
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DOI：
10.1001/jama.2016.9207
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发表时间：
2016-08-23
影响因子：
120.7
通讯作者：
Ramilo, Octavio
中科院分区：
文献类型：
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作者：
Mahajan, Prashant;Kuppermann, Nathan;Ramilo, Octavio
年幼的发热婴儿面临严重细菌感染的重大风险；然而，目前基于培养的诊断存在局限性。分析宿主对感染的表达模式（“RNA生物特征”）可能提供另一种诊断方法。目的评估RNA生物标记是否可以区分60天及以下发热婴儿有无严重细菌感染。设计、环境和参与者：前瞻性观察性研究，纳入2008年12月至2010年12月22个急诊科60天或60天以下发热婴儿的便利样本，这些婴儿接受了包括血液培养在内的实验室评估。随机选择有和没有细菌感染的婴儿样本进行RNA生物标记分析。发烧的健康婴儿作为对照。采集血样进行培养和RNA生物标记。应用生物信息学工具定义RNA生物特征，按感染类型对发热婴儿进行分类。暴露RNA生物特征与培养物的比较，用于区分有无细菌感染的发热婴儿以及有无细菌感染的菌血症婴儿。主要结果和测量方法：细菌感染经培养证实。比较常规实验室筛选试验和耶鲁观察量表（YOS）评分的RNA生物标记性能。结果：在1883例发热婴儿（中位年龄37天，55.7%为男孩）中，279例随机选择的婴儿（89例细菌感染，包括32例菌血症和15例尿路感染，190例无细菌感染）和19例发热健康婴儿的RNA生物特征被测量。鉴定出66个分类器基因，以87%（95% CI, 73%-95%）的敏感性和89%（95% CI, 81%-93%）的特异性来区分测试集中是否有细菌感染的婴儿。10个分类基因以94%（95% CI, 70%-100%）的敏感性和95%（95% CI, 88%-98%）的特异性区分了测试集中有菌血症的婴儿和没有细菌感染的婴儿。RNA生物特征在YOS评分上的增量C统计量为0.37 （95% CI, 0.30-0.43）。结论和相关性在这项初步研究中，定义了RNA生物标记来区分60天或以下的发热婴儿是否有细菌感染。需要在更大的人群中进行进一步的研究，以完善和验证测试准确性的估计，并评估RNA生物标记在实践中的临床应用。
IMPORTANCE Young febrile infants are at substantial risk of serious bacterial infections; however, the current culture-based diagnosis has limitations. Analysis of host expression patterns ("RNA biosignatures") in response to infections may provide an alternative diagnostic approach.OBJECTIVE To assess whether RNA biosignatures can distinguish febrile infants aged 60 days or younger with and without serious bacterial infections.DESIGN, SETTING, AND PARTICIPANTS Prospective observational study involving a convenience sample of febrile infants 60 days or younger evaluated for fever (temperature > 38 degrees C) in 22 emergency departments from December 2008 to December 2010 who underwent laboratory evaluations including blood cultures. A random sample of infants with and without bacterial infections was selected for RNA biosignature analysis. Afebrile healthy infants served as controls. Blood samples were collected for cultures and RNA biosignatures. Bioinformatics tools were applied to define RNA biosignatures to classify febrile infants by infection type.EXPOSURE RNA biosignatures compared with cultures for discriminating febrile infants with and without bacterial infections and infants with bacteremia from those without bacterial infections.MAIN OUTCOMES AND MEASURES Bacterial infection confirmed by culture. Performance of RNA biosignatures was compared with routine laboratory screening tests and Yale Observation Scale (YOS) scores.RESULTS Of 1883 febrile infants (median age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly selected infants (89 with bacterial infections-including 32 with bacteremia and 15 with urinary tract infections-and 190 without bacterial infections), and 19 afebrile healthy infants. Sixty-six classifier genes were identified that distinguished infants with and without bacterial infections in the test set with 87%(95% CI, 73%-95%) sensitivity and 89%(95% CI, 81%-93%) specificity. Ten classifier genes distinguished infants with bacteremia from those without bacterial infections in the test set with 94%(95% CI, 70%-100%) sensitivity and 95%(95% CI, 88%-98%) specificity. The incremental C statistic for the RNA biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43).CONCLUSIONS AND RELEVANCE In this preliminary study, RNA biosignatures were defined to distinguish febrile infants aged 60 days or younger with vs without bacterial infections. Further research with larger populations is needed to refine and validate the estimates of test accuracy and to assess the clinical utility of RNA biosignatures in practice.