早产儿肠道产超广谱β-内酰胺酶耐药菌定植及其与医院感染脓毒症的符合情况

Gut colonization of extended - spectrum β - lactamase - producing antibiotic - resistant bacteria in premature infants and its concordance with nosocomial sepsis

目的掌握早产儿肠道产超广谱β－内酰胺酶（ESBLs）耐药菌定植特点及影响因素，探讨其与医院感染脓毒症的符合情况。方法应用前瞻性研究方法，选取2013年5月至2014年5月入住福建省妇幼保健院新生儿科胎龄〈36周、入院年龄≤24 h、住院时间≥14 d的早产儿，出生第1、3、7天采集直肠拭子行产ESBLs耐药菌培养，之后每7 d采集1次，至出生第28天或出院，同时收集临床资料及血培养结果，进行统计学分析。结果共有300例早产儿纳入研究，221例（73.7%）早产儿肠道定植产ESBLs耐药菌。以产ESBLs肺炎克雷伯菌最常见。出生第1天肠道均无产ESBLs耐药菌定植，肠道耐药菌开始定植的时间出现在出生前2周。多因素Logistic逐步回归分析得出不同日龄出现肠道产ESBLs耐药菌定植的独立危险因素不同：出生第3天为母亲产前使用抗生素（OR＝2.091，95%CI：1.089～4.014）；第7天为出生后胃肠道喂养开始时间≥72 h（OR＝3.356，95%CI：1.540～7.312）；第14天为出生胎龄〈34周（OR＝4.011，95%CI：1.864～8.629）、出生体质量≤1 500 g（OR＝7.271，95%CI：3.301～16.016）、入住新生儿重症监护病房（OR＝2.675，95%CI：1.135～6.303）；第21天为出生体质量≤1 500 g（OR＝58.371，95%CI：6.517～522.854）；第28天为使用第3代头孢菌素治疗（OR＝48.000，95%CI：2.404～958.237）。使用青霉素类抗生素治疗（OR＝0.150，95%CI：0.059～0.386）是出生第7天的保护因素，口服益生菌治疗是第14天（OR＝0.221，95%CI：0.106～0.461）和第21天（OR＝0.061，95%CI：0.007～0.539）的保护因素（P均〈0.05）。肠道产ESBLs耐药菌定植的早产儿医院感染脓毒症发生率较肠道无产ESBLs耐药菌定植的明显升高（χ2＝25.155，P＝0.000）。医院感染脓毒症血培养产ESBLs耐药菌阳性病例中，80%直肠拭子培养出抗菌谱相同的同种耐药菌。结论早产儿肠道容易定植产ESBLs耐药菌，肠道产ESBLs耐药菌定植的早产儿发生医院感染脓毒症的风险增高，病原菌有明显的一致性，通过肠道耐药菌定植主动监测，可指导抗生素的正确选用，减少耐药菌传播。应针对危险因素采取措施以减少肠道耐药菌定植。

Objective To investigate the characteristics and risk factors of extended - spectrum β - lactamase （ESBLs） - producing antibiotic- resistant bacterial gut colonization in premature infants and to explore its concordance with nosocomial sepsis. Methods A prospective surveillance was performed in Fujian Provincial Maternity and Children＇s Health Hospital from May 2013 to May 2014. Preterm infants（ gestational age 〈 36 weeks ,admission within 24 h of birth and hospitalization time 〉t 14 d）were enrolled, and rectal swabs were collected for ESBLs -producing antibiotic - resistant bacteria culture, on the 1st ,3ra ,7 th day after birth, and every 7 days until the 28th day or discharge. The clinical data and the results of blood culture were collected, and statistical analysis was performed. Results A total of 300 patients were enrolled in this study, of whom 221 patients （73.7%） were identified as gut colonization with ES- BLs - producing bacteria, but the most common was ESBLs - producing klebsiella pneumoniae. No ESBLs - producing bacteria colonized in the gut on the first day after birth, and ESBLs - producing bacteria gut colonization mainly ap- peared in the first 2 weeks after birth. Multivariate Logistic regression indentified ：the use of antenatal antibiotics（ OR = 2.091,95 % CI：I. 089 -4. 014 ）was the independent risk factor for ESBLs - producing bacterial gut colonization in pre-mature infants on the 3rd day after birth, the age of first enteral feeding after birth t〉 72 h （ OR = 3. 356,95% CI： 1. 540 - 7.312 ） was the independent risk factor on the 7th day, gestational age 〈 34 weeks （ OR = 4.011,95 % CI： 1. 864 - 8. 629 ） , birth weight ≤1 500 g （ OR = 7.271,95 % CI：3. 301 - 16.016 ） and hospitalization in neonatal intensive care unit （NICU） after birth（ OR = 2. 675,95% CI：1. 135 -6. 303）were the independent risk factors on the 14th day, birthweight ≤1 500 g（ OR =58. 371,95% C1：6. 517 -522. 854）was the independent risk factor on the 21＇h day,using of the third generation cephalosporin（ OR =48. 000,95% CI：2. 404 -958. 237 ）was the independent risk factor on the 28th day. Application of penicillin antibiotics （ OR = 0. 150,95 % CI： 0.059 - 0.386 ） was the protective factor in reducing gut colonization with ESBLs - producing bacteria on the 7th day after birth,while application of probiotics was the pro-tective factor on the 14th day （ OR = 0. 221,95% CI： O. 106 - 0. 461 ） and 21th day （ OR =0. 061,95% CI： 0. 007 - 0. 539 ） （ all P 〈 0.05 ）. The premature infants with ESBLs - producing bacteria in the gut had higher incidence of clini- cal sepsis than those without ESBLs -producing bacteria in the gut （X^2 =25, 155,P = 0.000）. Among the cases the blood cultures were positive ,80% had the same species of ESBLs - producing bacteria and antibiognlm matched in the rectal swabs cultures. Conclusions The premature infants were more at risk of colonization with ESBLs - producing bacteria. The premature infants with ESBLs - producing bacteria in the gut had higher incidence of clinical sepsis. Colonization surveillance showed significant concordance with infection pathogens, and surveillance strategy for ESBLs - pro- ducing bacterial gut colonization can serve as an effective aid to empiric therapy, and reduce the spread of resistant organism. Taking measures to control risk factors can reduce the gut colonization with ESBLs - producing bacteria.