1 上海交通大学附属第六人民医院儿科，上海 201306
|| 上海市浦东新区科技发展基金 (PKJ2017-Y09)。
目的：研究发生宫外发育迟缓(extrauterine growth retardation，EUGR)的早产儿大便菌群中抗生素耐药基因的携带情况，探讨其临床意义。方法：选择2016年1月至2019年12月73例在上海市第六人民医院住院的胎龄≤34周或体重≤2 kg的早产儿为研究对象，其中50例发生EUGR，作为EUGR组，余下23例未发生EUGR作为对照组。采用宏基因功能测序的方法，对两组早产儿大便菌群中抗生素耐药基因的携带情况进行比较分析，并将其与肠道菌群作相关性分析。结果：两组间出生体重、平均胎龄、性别、剖宫产率的比较，差异无统计学意义(P>0.05)；EUGR组较对照组抗生素使用时间长、多种抗生素联用率高、有创机械通气率高、静脉营养时间长、住院时间长(均P<0.05)；EUGR组携带耐药基因277种，高于对照组(P<0.05)，并检测到8个差异性耐药基因(P<0.05)；耐药基因与菌群存在相关性，其中肺炎克雷伯杆菌、大肠杆菌、屎肠球菌丰度存在与其成显著正相关及负相关的耐药基因(P<0.05)；产气肠杆菌与耐药基因间的相关性分析中，只检测到与其呈负相关的耐药基因具有统计学差异(P<0.05)。结论：早产儿的EUGR发生率高，发生EUGR的早产儿携带的耐药基因种类也增多，且与部分肠道菌群呈显著的正相关或负相关，而这些早产儿住院期间抗生素的使用种类多、时间长等都可能与耐药基因的携带丰度增高有关，但是否对于早产儿后期生长发育等造成影响还需要进一步研究。
Analysis of antibiotic resistance genes in intestinal flora of premature infants with extrauterine growth retardation
CorrespondingAuthor: ZHANG Jinping
This work was supported by Shanghai Pudong New Area Science and Technology Development Fund, China (PKJ2017-Y09).
Objective: To investigate the clinical significance of carrying the antibiotic resistance genes in fecal flora of premature infants with extrauterine growth retardation. Methods: From January 2016 to December 2019, 73 premature infants with gestational age less than or equal to 34 weeks or weight less than or equal to 2 kg hospitalized in Shanghai Sixth People’s hospital were selected as the research objects, 50 cases of which developed EUGR as the EUGR group, and the remaining 23 cases of which as the control group. Macrogene functional sequencing was used to analyze the carrying status of antibiotic resistance genes in fecal flora and the correlation between the resistance genes and intestinal flora of two groups. Results: There was no significant difference in birth weight, average gestational age, gender and cesarean section rate between the two groups (P>0.05). Compared with the control group, EUGR group had longer antibiotic use time, higher combination rate of multiple antibiotics, higher invasive mechanical ventilation rate, longer intravenous nutrition time and longer hospital stay (P<0.05). The EUGR group carried 277 drug resistance genes, which were higher than those in the control group (P<0.05), and 8 differential drug resistance genes were detected (P<0.05). The abundance of Klebsiella pneumoniae, Escherichia coli and Enterococcus faecium had significant positive and negative correlation with drug resistance genes (P<0.05). In the correlation between Enterobacter aerogenes and drug resistance genes, only negative correlation genes were detected with statistical difference (P<0.05). Conclusion: The incidence of EUGR in premature infants is high, and the types of drug resistance genes in premature infants with EUGR are also increased, and there is a significant positive or negative correlation with some intestinal microflora. The types of antibiotics used for a long time in these premature infants during hospitalization may be related to the increased abundance of drug resistance genes. However, whether it affects the growth and development of premature infants in the later period needs further study.
extrauterine growth retardation; premature infants; intestinal flora; drug resistance genes