碳青霉烯类耐药肺炎克雷伯菌耐药机制及同源性研究
发布时间:2018-01-10 07:16
本文关键词:碳青霉烯类耐药肺炎克雷伯菌耐药机制及同源性研究 出处:《浙江大学》2015年硕士论文 论文类型:学位论文
更多相关文章: 碳青霉烯类 肺炎克雷伯菌 耐药 碳青霉烯酶 脉冲场凝胶电泳 多位点序列分型 全基因组测序 同源性
【摘要】:肺炎克雷伯菌是院内获得性感染中最为常见的致病菌之一,主要引起肺炎、败血症、尿路感染、肝脓肿及腹膜炎等。随着抗菌药物的广泛使用,尤其是碳青霉烯类抗生素的大量或不合理使用,碳青霉烯类耐药肺炎克雷伯菌(Carbapenem-resistant Klebsiella pneumonia, CRKP)呈现全球播散趋势,在我国分离率逐年攀升,对临床治疗带来极大挑战。本研究旨在探讨本院CRKP院内感染相关危险因素和耐药机制,并分析其同源性和院内感染流行现状,为CR KP的防控提供科学的理论依据。 本研究收集了来自本院8个临床科室的30株CRKP,制定统一调查表收集临床资料并进行分析。采用纸片扩散法进行常见药物的体外敏感性实验,并用改良Hodge试验检测所有菌株是否产碳青霉烯酶。所有菌株均利用脉冲场凝胶电泳(Pulsed field gel electrophoresis, PFGE)和多位点序列分型(Multilocus sequencetyping,MLST)两种技术进行同源性分析,部分菌株进行全基因组测序(Whole genome sequencing, WGS)分析亲缘关系远近。 临床资料显示30位感染患者的平均年龄较高(72±15岁),各项病情评分指标均显示病情严重。基础疾病中神经系统疾病、糖尿病和心力衰竭患者占了前三位。而有90%的患者在三个月内使用过p-内酰胺酶抑制剂合剂,50%多的患者使用过碳青霉烯类。近三个月内绝大多数患者曾留置导管,例如导尿管、深静脉导管和气管导管等。体外药物敏感性实验显示所有菌株对美罗培南和厄他培南耐药,除一株对亚胺培南为中介外其余也全部耐药。对三、四代头孢、复合制剂所有菌株均耐药。而对环丙沙星、庆大霉素和阿米卡星的耐药率分别是90.0%、97.0%和87.0%。所有菌株对多粘菌素E和替加环素均无耐药。耐药酶基因检测结果提示30株肺炎克雷伯菌在携带blaKPC-2的同时均带有blasHV。此外,有部分菌株还同时带有blacTX-M和blaTEM。PFGE将所有菌株分为A-H8个克隆群,主要有2个克隆群出现院内播散,分别是A和C克隆群。MLST分析得到5种序列型(Sequence type, ST),其中23株属于ST11,3株属于ST437,2株属于ST290,另外两株分别为ST133和ST15。5株A克隆(ST11)菌株的全基因组测序将5株细菌分为3个不同的群组(2株:2株:1株),同一群组的菌株为一簇,亲缘关系密切,单独的那株自成一簇,与前两簇关系疏远。因此,WGS较PFGE和MLST更深入的揭示了菌株的遗传背景,更利于菌株的溯源追踪。 综上所述,CRKP感染患者具有多种危险因素,患者预后情况与多种危险因素和治疗相关。初始经验性抗感染治疗应根据感染危险因素进行选择,并及时综合分析患者病情,结合药敏结果进行目标治疗。产肺炎克雷伯菌碳青霉烯酶(Klebsiella pneumoniae carbapenemase, KPC)2型是本院CRKP耐药的重要原因,多种耐药基因的共同携带导致其多重耐药表型。ST11型克隆播散是本院感染流行的重要原因,应加强医院感染监控力度。
[Abstract]:Klebsiella pneumoniae is one of the most common pathogens in nosocomial infection, which mainly causes pneumonia, sepsis, urinary tract infection, liver abscess and peritonitis. In particular, a large number of carbapenem antibiotics or unreasonable use. Carbapenem resistant Klebsiella pneumonia. CRKP) presents a global spread trend, and the isolation rate in China is increasing year by year, which brings great challenge to clinical treatment. This study aims to explore the risk factors and drug resistance mechanism of hospital CRKP nosocomial infection. The homology of CR KP and the prevalence of nosocomial infection were analyzed in order to provide a scientific theoretical basis for the prevention and control of CR KP. In this study, 30 CRKPs from 8 clinical departments were collected, and a unified questionnaire was developed to collect and analyze the clinical data. In vitro sensitivity tests of common drugs were carried out by disk diffusion method. The improved Hodge test was used to detect whether all strains produced carbapenem. All strains were detected by pulsed field gel electrophoresis (PGE). Pulsed field gel electrophoresis. PFGE and multilocus sequencing typing (MLST) were used for homology analysis. Some strains were analyzed by whole genome sequencing (WGS). Clinical data showed that the average age of 30 infected patients was higher than 72 卤15 years old. Diabetes and heart failure accounted for the top three. 90% of the patients had used plactamase inhibitors within three months. More than 50% patients have used carbapenems. The vast majority of patients have had catheters, such as catheters, in the last three months. In vitro drug sensitivity tests showed that all the strains were resistant to meropenem and ertapenem, except one for imipenem. All strains of compound preparation were resistant to ciprofloxacin, gentamicin and amikacin, respectively. The resistance rates of ciprofloxacin, gentamicin and amikacin were 90.0%. 97.0% and 87.0. All strains were not resistant to polymyxin E and tegacyclin. The results of enzyme resistance gene analysis showed that all 30 strains of Klebsiella pneumoniae carried blaKPC-2 with b. LasHV. in addition. Some strains also carry blacTX-M and blaTEM.PFGE to divide all strains into A-H 8 clone groups, mainly 2 clones spread in the hospital. According to the analysis of A and C clones. MLST, 5 kinds of sequence type and STN were obtained, of which 23 belonged to ST11N, 3 of which belonged to ST437. Two strains belong to ST290. The other two strains, ST133 and ST15.5 strain A clone ST11, were sequenced and divided into three different groups: 2 strains: 2 strains: 1 strain). The strains of the same group are a cluster, closely related to each other, and the single strain is isolated from the first two clusters. Therefore, the genetic background of the strain is revealed more deeply by WGS than by PFGE and MLST. More conducive to traceability of the strain tracking. In conclusion, there are many risk factors in patients with CRKP infection, and the prognosis of patients is related to many risk factors and treatment. The initial empirical anti-infection therapy should be based on the risk factors of infection. And timely comprehensive analysis of the patient's condition. Combined with the results of drug sensitivity, Klebsiella pneumoniae carbapenemase was produced by Klebsiella pneumoniae carbapenemase, Klebsiella pneumoniae carbapenemase was produced by Klebsiella pneumoniae. KPC)2 type is an important cause of CRKP resistance in our hospital. The common carrying of multidrug resistance genes leads to the spread of multidrug resistance phenotype. ST11 is an important reason for the prevalence of infection in our hospital. Hospital infection monitoring should be strengthened.
【学位授予单位】:浙江大学
【学位级别】:硕士
【学位授予年份】:2015
【分类号】:R446.5
【参考文献】
相关期刊论文 前2条
1 卓超;苏丹虹;朱德妹;胡付品;汪复;阮斐怡;孙自镛;简翠;徐英春;孙宏莉;倪语星;孙景勇;俞云松;杨青;王传清;薛建昌;张泓;李万华;胡云健;艾效曼;贾蓓;黄文祥;魏莲花;吴玲;张朝霞;季萍;;2007年CHINET大肠埃希菌和克雷伯菌属耐药性监测[J];中国感染与化疗杂志;2009年03期
2 徐英春;肖永红;卓超;郑波;王辉;杨启文;;中国碳青霉烯类耐药肠杆菌科细菌的流行病学和防控策略[J];中国执业药师;2013年04期
,本文编号:1404329
本文链接:https://www.wllwen.com/huliyixuelunwen/1404329.html
最近更新
教材专著