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一种用于检测早产儿细菌感染的新方法:联合使用血液和唾液中的炎症标志物。

A novel method to detect bacterial infection in premature infants: Using a combination of inflammatory markers in blood and saliva.

机构信息

Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang, Gung University College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang, Gung University College of Medicine, Kaohsiung, Taiwan.

出版信息

J Microbiol Immunol Infect. 2020 Dec;53(6):892-899. doi: 10.1016/j.jmii.2019.11.002. Epub 2019 Dec 14.

Abstract

BACKGROUND

Opportunistic infection leads to high morbidity and mortality in premature babies due to their immature immune system. Biomarkers in blood have been reported to detect bacterial infection in neonates. However, serial blood exams pose iatrogenic anemia in premature babies. Thus, this study aimed to identify cytokines in saliva, which can help to diagnose bacterial infection in premature babies via a non-invasive method.

METHODS

Premature neonates were enrolled from Aug. 2012 to Feb. 2015 after completing informed consent. Babies with congenital anomalies, bronchopulmonary dysplasia, necrotizing enterocolitis and any surgical indicated diseases were excluded. Salivary samples collection and septic work-up were performed when bacterial infection was clinically suspected, as well as one week after antimicrobial treatment. The level of salivary cytokines was detected by MILLPLEX® MAP and analyzed by Mann-Whitney U test.

RESULTS

There were 16 episodes of bacterial infection in 10 cases. Culture-positive group had significantly higher levels of salivary Interleukin (IL) 6, IL-8, macrophage inflammatory protein (MIP)1α, MIP-1β and tumor necrosis factor (TNF)-α than that in the culture-negative group (p = 0.002, 0.006, 0.001, <0.001, 0.009), and blood C-reactive protein and sugar as well (p < 0.001, 0.026). After adjusting postmenstrual age by logistic regression, blood sugar level was the most significant biomarker (p = 0.019). In combination of blood and salivary biomarkers, blood sugar higher than 67 mg/dL and salivary IL-6 higher than 367.25 pg/mL concurrently, would accurately detect bacterial infection in premature babies.

CONCLUSION

This non-invasive method might help us to accurately diagnose bacterial infection in premature babies.

摘要

背景

机会性感染会导致早产儿发病率和死亡率升高,这是由于他们的免疫系统尚未成熟。已有研究报道血液生物标志物可用于检测新生儿的细菌感染。然而,频繁的血液检查会导致早产儿医源性贫血。因此,本研究旨在寻找唾液中的细胞因子,通过非侵入性方法帮助诊断早产儿的细菌感染。

方法

本研究于 2012 年 8 月至 2015 年 2 月完成知情同意后,纳入早产儿。排除患有先天畸形、支气管肺发育不良、坏死性小肠结肠炎和任何需要手术的疾病的婴儿。当临床怀疑有细菌感染时,以及在抗菌治疗后一周,进行唾液样本采集和脓毒症检查。通过 MILLPLEX®MAP 检测唾液细胞因子水平,并采用 Mann-Whitney U 检验进行分析。

结果

10 例患儿中共有 16 例发生细菌感染。培养阳性组的唾液白细胞介素(IL)6、IL-8、巨噬细胞炎症蛋白(MIP)1α、MIP-1β和肿瘤坏死因子(TNF)-α水平明显高于培养阴性组(p=0.002、0.006、0.001、<0.001、0.009),且血液 C 反应蛋白和血糖水平也明显高于培养阴性组(p<0.001、0.026)。通过逻辑回归调整胎龄后,血糖水平是最显著的生物标志物(p=0.019)。联合血液和唾液生物标志物,当血糖高于 67mg/dL 且唾液 IL-6 高于 367.25pg/mL 时,可准确检测早产儿的细菌感染。

结论

这种非侵入性方法可能有助于我们准确诊断早产儿的细菌感染。

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