早产极低出生体重儿肠道克雷伯菌属定植与肺炎克雷伯菌感染的相关性研究

The relationship of intestinal Klebsiella colonization and Klebsiella pneumoniae infection in very low birth weight infants

目的探讨早产极低出生体重儿(very low birth weight infant,VLBWI)肠道克雷伯菌属定植与肺炎克雷伯菌感染的相关性。方法采用前瞻性巢式病例对照研究,选择2015年1~12月收入深圳市宝安区妇幼保健院新生儿重症监护室的VLBWI为研究对象,收集生后第1、7、14、28、180天的粪便样本,采用Illumina MiSeq平台双端测序模式对粪便样本细菌DNA进行16S rRNA基因高通量测序及生物信息分析。同时记录临床信息,根据患儿住院期间是否发生肺炎克雷伯菌感染分为感染组与对照组,比较两组肠道菌群多样性及克雷伯菌属相对丰度。结果共纳入53例VLBWI,其中感染组13例(肺炎克雷伯菌败血症8例、肺炎5例),对照组40例,感染发生时间为生后(19.8±1.6)d,95%CI 16.5~23.0。两组VLBWI生后第7、14、28天肠道克雷伯菌属丰度均高于第1、180天(P<0.05)。生后第14天时感染组肠道克雷伯菌属相对丰度高于对照组(0.66±0.38比0.37±0.40,P=0.040),其余时间点两组差异无统计学意义(P>0.05)。感染组气管插管机械通气比例高于对照组(84.6%比37.5%,P<0.05),其他临床资料两组间差异无统计学意义(P>0.05)。两组各时间点多样性指数比较差异无统计学意义(P>0.05)。结论在肺炎克雷伯菌临床感染发生前VLBWI肠道克雷伯菌属丰度已明显增加,减少克雷伯菌属在肠道的定植可能有助于降低肺炎克雷伯菌临床感染。

Objective To study the relationship between the intestinal Klebsiella colonization and Klebsiella pneumoniae infection in very low birth weight infant(VLBWI).Method From January to December 2015,VLBWI admitted to the NICU of our hospital were enrolled in a prospective nested case-control study.Their stool samples were collected on 1,7,14,28 and 180 d.Bacterial DNA in stool samples were examined using the Illumina MiSeq platform double-end sequencing mode for 16S rRNA gene high-throughput sequencing and biological information analysis.The infants were assigned into the infection group and the control group according to whether Klebsiella pneumoniae infection occurred during their hospital stay.The intestinal flora diversity and Klebsiella relative abundance between the two groups were compared.Result A total of 53 cases of VLBWI were included,including 13 cases in the infection group(8 cases of Klebsiella pneumoniae sepsis and 5 cases of pneumonia)and 40 cases in the control group.The infection occurred at postnatal(19.8±1.6)d(95%CI 16.5~23.0).The relative abundances of Klebsiella on 7 d,14 d and 28 d were higher than 1d and 180 d in both groups(P<0.05).The relative abundance of Klebsiella in the infected group was higher than the control group on the 14 d(0.66±0.38 vs.0.37±0.40,P=0.040),and no significant differences existed between the two groups at all the other days(P>0.05).The incidence of mechanical ventilation in the infected group was higher than the control group(84.6%vs.37.5%,P<0.05).No statistically significant differences existed in other clinical data between the two groups(P>0.05).No significant differences existed in the intestinal flora diversity index at each time point between the two groups(P>0.05).Conclusion Before the occurrence of Klebsiella pneumoniae infection,the relative abundance of Klebsiella in the intestines of VLBWI has increased significantly.Reducing Klebsiella colonization in the intestines may help reduce the clinical infection of Klebsiella pneumoniae.