岩藻糖基化人乳低聚糖在新生儿无乳链球菌肺炎治疗中的作用

The role of fucosylated human milk oligosaccharide in the treatment of neonatal Streptococcus agalactiae pneumonia

目的探讨岩藻糖基化人乳低聚糖在新生儿无乳链球菌肺炎中的治疗作用。方法收集本院2015年7月至2017年2月痰培养阳性新生儿无乳链球菌、大肠埃希菌和肺炎克雷伯菌感染性肺炎病例,分析不同喂养方式、不同病原类别肺炎在住院时间、炎症、并发症等指标差异,探讨岩藻糖基化人乳低聚糖对无乳链球菌感染的独特治疗作用;使用含有不同浓度岩藻糖基化人乳低聚糖的培养基对无乳链球菌进行培养,研究岩藻糖基化人乳低聚糖抑制无乳链球菌的最佳浓度;分别使用岩藻糖基化人乳低聚糖或酸性人乳低聚糖加入培养基中对无乳链球菌、大肠埃希菌、肺炎克雷伯菌进行培养,进一步探讨岩藻糖基化人乳低聚糖对无乳链球菌的独特抑制作用。结果无乳链球菌肺炎患儿,母乳喂养组的住院时间较人工喂养组住院时间减少[(8.35±0.77)d vs(10.91±0.54)d,t=1.557 676,P<0.05)],PCT值较人工喂养组低[(2.38±0.63)ng/mL vs(8.69±2.23)ng/mL,t=1.419 964,P<0.05],白细胞计数较人工喂养组低[(13.28±1.08)×10^9/L vs(16.16±0.98)×10^9/L,t=1.878 447,P<0.05],脑膜炎发生率较人工喂养组低(5%vs 35%,χ^2=5.601 353,P<0.05),呼吸机使用率较人工喂养组低(10.0%vs 36.4%,χ^2=4.005 042,P<0.05);大肠埃希菌肺炎患儿、肺炎克雷伯菌肺炎患儿,母乳喂养组与人工喂养组比较,住院时间稍减少,PCT值、白细胞计数、脑膜炎发生率和呼吸机使用率均有所降低,差异无统计学意义;细菌培养实验发现岩藻糖基化人乳低聚糖在2.5 mg/L浓度的时候可以明显抑制无乳链球菌的生长,对大肠埃希菌和肺炎克雷伯菌无明显抑制作用,酸性人乳低聚糖对3种细菌均无抑制作用。结论岩藻糖基化人乳低聚糖可以明显抑制无乳链球菌的生长,可能成为未来无乳链球菌感染性肺炎治疗中新的靶点,值得深入研究。

Objective To investigate the efficacy of fucosylated human milk oligosaccharides(FHMOs) in neonatal Streptococcus agalactiae pneumonia. Methods The cases of neonatal pneumonia caused by Streptococcus agalactiae, Escherichia coli and Klebsiella pneumoniae with positive sputum culturing results in our hospital from July 2015 to February 2017 were collected. The differences in hospital stay, inflammation indexes and complications among different feeding methods were analyzed to explore the unique therapeutic effect of FHMOs on Streptococcus agalactiae infection. Streptococcus agalactiae was cultured in a medium containing different concentrations of FHMOs to determine the optimal inhibitory concentration of FHMOs. Streptococcus agalactiae, Escherichia coli and Klebsiella pneumoniae were cultured in the medium containing FHMOs or acidic human milk oligosaccharide to determine the unique inhibitory effect of FHMOs on Streptococcus agalactiae. Results In children with Streptococcus agalactiae infection, the length of hospital stay in the breast-feeding group was lower than that in the artificial-feeding group(8.35±0.77 days vs 10.91±0.54 days, t=1.557 676, P<0.05);the PCT value in the breast-feeding group was lower than that in the artificial-feeding group(2.38±0.63 ng/mL vs 8.69±2.23 ng/mL, t=1.419 964, P<0.05);the white blood cell count in breast-feeding group was lower than that in artificial feeding group [(13.28±1.08)×10^9/L vs(16.16±0.98)×10^9/L, t=1.878 447, P<0.05];the incidence of meningitis in the breast-feeding group was lower than that in the artificial-feeding group(5% vs 35%, χ^2=5.601 353, P<0.05);and the rate of ventilator use in the breast-feeding group was lower than that in the artificial-feeding group(10.0% vs 36.4%, χ^2=4.005 042, P<0.05). In the children with Escherichia coli pneumonia or Klebsiella pneumoniae infection, compared with the artificial feeding group, the duration of hospitalization in breast-feeding group slightly reduced;the PCT value, white blood cell count, incidence of meningitis and ventilator use reduced, but there were no statistical differences between groups. Bacterial culture showed that FHMOs at the concentration of 2.5 mg/L significantly inhibited the growth of Streptococcus agalactiae, but had no significant inhibitory effect on Escherichia coli and Klebsiella pneumoniae, while acidic human lactooligosaccharides had no inhibitory effect on the three bacteria. Conclusion FHMOs can significantly inhibit the growth of Streptococcus agalactiae, and may become a new option for the treatment of Streptococcus agalactiae infection in the future.