本文選題：艱難梭菌感染 + 無癥狀定植�。� 參考：《上海交通大學》2015年碩士論文

【摘要】：目的:本課題旨在分析老年住院患者艱難梭菌感染(Clostridium difficile infection,CDI)的臨床特征并評估其相關(guān)的危險因素,尋找臨床與社區(qū)分離的艱難梭菌在毒素型、基因分型和耐藥性上的差異,以及探究艱難梭菌感染患者和無癥狀艱難梭菌定植者腸道菌群的改變,為艱難梭菌相關(guān)性疾病的預防、治療和監(jiān)控提供參考和依據(jù)。方法:第一部分,對2010年12月至2013年5月間上海某三甲醫(yī)院大于60歲的202名老年住院患者的病史資料進行回顧性分析,其中包含52名CDI患者(病例組)和隨機選取的150名非CDI患者(對照組)。采用適當?shù)慕y(tǒng)計學方法比較病例組和對照組之間臨床表現(xiàn)、實驗室指標和治療用藥等方面的差異,并用logistic回歸分析評估一系列與老年住院患者艱難梭菌感染相關(guān)的危險因素。第二部分,對來源于臨床CDI患者的45株艱難梭菌和來源于社區(qū)無癥狀艱難梭菌定植者的12株艱難梭菌(共計57株)進行毒素基因檢測,并通過多位點序列分型技術(shù)實現(xiàn)菌株的基因分型,同時采用瓊脂稀釋法分析菌株對8種抗菌藥物(包括:克林霉素、四環(huán)素、頭孢西丁、頭孢噻肟、莫西沙星、亞胺培南、甲硝唑和萬古霉素)的敏感性。第三部分,我們收集8名CDI患者、8名無癥狀艱難梭菌定植者和9名健康受試者的新鮮糞便樣本,采用16S r RNA基因高通量焦磷酸測序法對三組樣本進行腸道菌群分析,并借助生物信息學技術(shù),從細菌“門”和“屬”水平比較CDI患者、無癥狀艱難梭菌定植者和健康受試者間腸道菌群組成的差異。結(jié)果:在老年住院患者中,CDI患者相比非CDI患者表現(xiàn)出白細胞計數(shù)升高、血清白蛋白含量降低、住院時間延長、死亡率上升等特征。多變量分析表明,老年住院患者艱難梭菌感染與血清肌酐水平(OR 1.004;95%CI 1.001-1.008)、共病數(shù)量(OR2.573;95%CI 1.353-4.892)、外科手術(shù)史(OR 6.132;95%CI 2.594-14.493)、胃腸道疾病(OR 4.670;95%CI 2.002-10.895)和抗生素使用(OR 6.718;95%CI 2.846-15.859)密切相關(guān)。臨床分離的艱難梭菌菌株均產(chǎn)毒素,毒素型以A+B+型為主,ST-37型為流行克隆,占33.3%;而社區(qū)分離菌株中含無毒株,且存在某些與臨床分離菌株相同的ST型。此外,臨床分離菌株的多重耐藥率高于社區(qū)分離菌株,尤其對氟喹諾酮類藥物的耐藥率明顯上升。CDI患者和無癥狀艱難梭菌定植者存在不同程度的腸道菌群失調(diào),與健康人相比,他們的腸道微生物豐度和多樣性均明顯降低,腸道菌群組成中擬桿菌門和厚壁菌門的比例下降、變形菌門的比例升高,且缺失某些產(chǎn)丁酸鹽的腸道正常共生菌。主坐標分析顯示,CDI患者與無癥狀艱難梭菌定植者之間的腸道菌群結(jié)構(gòu)也存在明顯差異。結(jié)論:血清肌酐水平升高、共病數(shù)量增加、外科手術(shù)史、胃腸道疾病和抗生素使用是老年住院患者艱難梭菌感染的危險因素。多重耐藥性可能是導致CDI流行傳播的重要原因之一,而社區(qū)無癥狀艱難梭菌定植者很可能成為臨床艱難梭菌感染的潛在來源。腸道菌群的改變不僅影響CDI的發(fā)生,還對艱難梭菌相關(guān)性疾病狀態(tài)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.
【學位授予單位】：上海交通大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R446.5

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