肠道定植耐碳青霉烯肠杆菌科细菌(CRE)与感染病原菌关系

The relationship between carbapenem-resistant Enterobacteriaceae(CRE)colonized in intestinal tract and pathogenic bacteria of infection

目的以肠道定植碳青霉烯类耐药肠杆菌科细菌(carbapenem resistance Enterobacteriaceae,CRE)与同一患者后期感染细菌的关系为出发点,同源性检测和耐药基因筛查为中心,从重症医学科(intensive care unit,ICU)患者肠道CRE的定植情况、CRE肠道定植与后期感染的关系层次上,进行CRE防治的应用基础研究,从而为临床及时有效的抗感染治疗提供一定指导。方法收集2018—2019年来自ICU病房及由其他科室转入ICU的共11位患者的临床资料,分别分离同一患者肠道定植CRE菌株和后期其他感染部位的菌株,对所有菌株进行药物敏感性试验和耐药基因携带情况检测,采用多位点序列分析(MLST)、脉冲场凝胶电泳(PAGE)试验的方法对定植CRE菌株和后期其他感染部位的菌株进行同源性分析。结果95位ICU患者中有19位患者肠道CRE筛查阳性,定植率为20.00%。其中发生后期其他部位感染的患者11位,目标菌株耐碳青霉烯酶基因检测结果显示22株菌株中有21株检出耐药基因,占95.45%(21/22)。其中19株检出KPC-2耐药基因,阳性率为86.36%(19/22);2株检出NDM-1耐药基因,阳性率为9.09%(2/22)。其他碳青霉烯酶基因检测均为阴性。22株目标菌的MLST分型共分为3个型,主要为ST11型,11位患者中除了1位患者的后期感染菌株与定植菌株差异明显外,其余患者的肠道定植菌株与后期感染菌株均为相同的ST型;PAGE检出22株菌的分型可分为A群和B群,共7个型别,其中7位患者的肠道定植菌株与后期感染菌株之间条带位置与数目相同,视为同一克隆型,3位患者的肠道定植菌株与后期感染菌株条带有2~3个差异,同源性极高,视为高度相关菌株;1位患者的肠道定植菌株与后期感染菌株的条带异超过7条,视为不相关菌株。结论ICU患者定植率高,应加强入院CRE定植筛查;ICU患者部位检出的定植及感染CRE菌株MIC值高,为高耐药性菌株;ICU患者发生CRE感染的菌株与自身定植的菌株有极高的同源性。

Objective Starting from the relationship between intestinal colonized carbapenem-resistant Enterobacteriaceae(CRE)and later infected bacteria in the same patient,our study focused on homology detection and drug resistant gene screening.From the level of intestinal CRE colonization in Intensive Care Unit(ICU)patients and the relationship between intestinal CRE colonization and late infection,basic applied research on the prevention and treatment of CRE was carried out,so as to provide certain guidance for timely and effective clinical anti-infection treatment.Methods A total of 11 patients in ICU between 2018 and 2019 were retrospectively included.CRE colonized in intestinal tracts of ICU patients and bacterial strains in other sites of later infections were isolated to test the homology,drug sensitivity,and drug-resistant genes using multi locus sequence analysis(MLST)and pulsed field gel electrophoresis(PAGE).Results Positive intestinal CRE was identified in 19/95(20.00%)ICU patients.Among 19 patients,11 had later infections of other sites.A total of 22 strains were isolated from the 19 patients.Carbapenemresistant genes were detected in 21/22(95.45%)strains,including KPC-2-resistant gene detected in 19/22(86.36%)strains and NDM-1 resistant gene detected in 2/22(9.09%)strains.Other carbapenem-resistant genes were negative.According to the MLST typing,22 target strains were divided into three types,and they mainly belonged to the ST11 type.Among the 11 patients,the intestinal colonization and colonization strains all belonged to the same ST type,except for one patient where obvious difference between the late infection strains and colonization strains was found.According to the PAGE results,22 strains could be divided into group A and B.There were seven types in group A and group B.Among them,seven strains of colonization in intestinal tracts and late infections in ICU patients with the same number of stripe locations were viewed as the same cloning.Three strains of colonization in intestinal tracts of ICU patients with late infections with two or three different stripe locations,showing an extremely high homology,were treated as highly related strains.The intestinal colonization strains of one patient,which differed from the late infection strains by more than 7 bands,were irrelevant strains.Conclusion The colonization rate of ICU patients is high,and the screening of CRE in admission should be highlighted.The MIC values of colonized and infected CRE strains detected in ICU patients are high,indicating high risk of drug resistance.The strains of CRE infection in ICU patients are highly homologous to the self-colonized strains.