艰难梭菌感染的临床特征、分子流行病学及肠道菌群研究

发布时间：2018-07-09 23:23

本文选题：艰难梭菌感染 + 无症状定植　；参考：《上海交通大学》2015年硕士论文

【摘要】：目的:本课题旨在分析老年住院患者艰难梭菌感染(Clostridium difficile infection,CDI)的临床特征并评估其相关的危险因素,寻找临床与社区分离的艰难梭菌在毒素型、基因分型和耐药性上的差异,以及探究艰难梭菌感染患者和无症状艰难梭菌定植者肠道菌群的改变,为艰难梭菌相关性疾病的预防、治疗和监控提供参考和依据。方法:第一部分,对2010年12月至2013年5月间上海某三甲医院大于60岁的202名老年住院患者的病史资料进行回顾性分析,其中包含52名CDI患者(病例组)和随机选取的150名非CDI患者(对照组)。采用适当的统计学方法比较病例组和对照组之间临床表现、实验室指标和治疗用药等方面的差异,并用logistic回归分析评估一系列与老年住院患者艰难梭菌感染相关的危险因素。第二部分,对来源于临床CDI患者的45株艰难梭菌和来源于社区无症状艰难梭菌定植者的12株艰难梭菌(共计57株)进行毒素基因检测,并通过多位点序列分型技术实现菌株的基因分型,同时采用琼脂稀释法分析菌株对8种抗菌药物(包括:克林霉素、四环素、头孢西丁、头孢噻肟、莫西沙星、亚胺培南、甲硝唑和万古霉素)的敏感性。第三部分,我们收集8名CDI患者、8名无症状艰难梭菌定植者和9名健康受试者的新鲜粪便样本,采用16S r RNA基因高通量焦磷酸测序法对三组样本进行肠道菌群分析,并借助生物信息学技术,从细菌“门”和“属”水平比较CDI患者、无症状艰难梭菌定植者和健康受试者间肠道菌群组成的差异。结果:在老年住院患者中,CDI患者相比非CDI患者表现出白细胞计数升高、血清白蛋白含量降低、住院时间延长、死亡率上升等特征。多变量分析表明,老年住院患者艰难梭菌感染与血清肌酐水平(OR 1.004;95%CI 1.001-1.008)、共病数量(OR2.573;95%CI 1.353-4.892)、外科手术史(OR 6.132;95%CI 2.594-14.493)、胃肠道疾病(OR 4.670;95%CI 2.002-10.895)和抗生素使用(OR 6.718;95%CI 2.846-15.859)密切相关。临床分离的艰难梭菌菌株均产毒素,毒素型以A+B+型为主,ST-37型为流行克隆,占33.3%;而社区分离菌株中含无毒株,且存在某些与临床分离菌株相同的ST型。此外,临床分离菌株的多重耐药率高于社区分离菌株,尤其对氟喹诺酮类药物的耐药率明显上升。CDI患者和无症状艰难梭菌定植者存在不同程度的肠道菌群失调,与健康人相比,他们的肠道微生物丰度和多样性均明显降低,肠道菌群组成中拟杆菌门和厚壁菌门的比例下降、变形菌门的比例升高,且缺失某些产丁酸盐的肠道正常共生菌。主坐标分析显示,CDI患者与无症状艰难梭菌定植者之间的肠道菌群结构也存在明显差异。结论:血清肌酐水平升高、共病数量增加、外科手术史、胃肠道疾病和抗生素使用是老年住院患者艰难梭菌感染的危险因素。多重耐药性可能是导致CDI流行传播的重要原因之一,而社区无症状艰难梭菌定植者很可能成为临床艰难梭菌感染的潜在来源。肠道菌群的改变不仅影响CDI的发生,还对艰难梭菌相关性疾病状态具有一定的指示作用。
[Abstract]:Objective: to analyze the clinical characteristics of Clostridium difficile infection (CDI) in elderly hospitalized patients and evaluate the related risk factors, and to find out the differences in the toxin type, genotyping and drug resistance of Clostridium difficile isolated from clinical and community, as well as to explore the patients with Clostridium difficile and the asymptomatic difficult shuttle. The changes in intestinal microflora of bacterial colonies were provided for the prevention, treatment and monitoring of Clostridium difficile related diseases. Methods: the first part was a retrospective analysis of the medical history data of 202 elderly hospitalized patients older than 60 years old in a three a hospital in Shanghai, Shanghai, from December 2010 to May 2013, including 52 patients (case groups) and 52 patients. A random selection of 150 non CDI patients (control group) was used to compare the clinical manifestations, laboratory indicators, and drug use differences between the case group and the control group, and to evaluate the risk factors associated with the infection of Clostridium difficile in elderly hospitalized patients by logistic regression analysis. 45 strains of Clostridium difficile and 12 Clostridium difficile (57 strains) of Clostridium difficile from community asymptomatic Clostridium difficile colonization were detected in clinical CDI patients, and gene typing was realized by multipoint sequence typing, and the agar dilution method was used to analyze 8 kinds of antimicrobial agents (including clindamycin, tetracycline, head). The sensitivity of Sidin, cefotaxime, moxifloxacin, imipenem, metronidazole and vancomycin. Third, 8 CDI patients, 8 asymptomatic Clostridium difficile coloner and 9 healthy subjects were collected, and three groups of samples were analyzed by 16S R RNA gene high pyrosequencing method. Bioinformatics technology, the difference in the intestinal flora composition of CDI patients, asymptomatic Clostridium difficile colonization and healthy subjects. Results: in elderly hospitalized patients, CDI patients showed higher leukocyte count, lower serum albumin content, longer hospitalization time and death than non CDI patients. Multivariable analysis showed that the prevalence of Clostridium difficile infection and serum creatinine level (OR 1.004; 95%CI 1.001-1.008), the total number of diseases (OR2.573; 95%CI 1.353-4.892), the history of surgical operation (OR 6.132; 95%CI 2.594-14.493), gastrointestinal diseases (OR 4.670; 95%CI 2.002-10.895) and antibiotic use (6.718; 859) closely related. Clinical isolates of Clostridium difficile strains produce toxin, toxin type is A+B+ type, ST-37 type is popular clones, accounting for 33.3%, and community isolates contain nontoxic strains, and there are some ST types that are the same as clinical isolates. In addition, the multidrug resistance rate of clinical isolates is higher than that of community isolated strains, especially fluoroquinolones. The drug resistance rate of the drugs increased significantly in the.CDI patients and the asymptomatic Clostridium difficile coloner in different degrees of intestinal flora imbalance. Compared with the healthy people, their intestinal microflora and diversity were significantly decreased, the ratio of the bacteriobacteria and the thick wall bacteria in the intestinal flora decreased, the proportion of the deformable bacteria door increased, and a certain lack of bacteria was found. The main coordinate analysis showed that the intestinal flora structure between the CDI patients and the asymptomatic Clostridium difficile colonization was also significantly different. Conclusion: the level of serum creatinine increased, the number of CO diseases increased, the surgical history, the gastrointestinal disease and the use of antibiotics were the risk of Clostridium difficile infection in elderly hospitalized patients. Risk factors. Multiple drug resistance may be one of the important causes of the epidemic of CDI, and the community asymptomatic Clostridium difficile coloner is likely to be a potential source of Clostridium difficile infection. The changes in intestinal flora not only affect the occurrence of CDI, but also have a certain indication of the disease state of Clostridium difficile.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R446.5

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