【作者】 王杰；

【导师】 周建英；

【作者基本信息】 浙江大学 ， 内科学， 2004， 硕士

【摘要】 一、课题背景 铜绿假单胞菌（Pseudomonas aeruginosa），又称绿脓杆菌，是常见的医院感染致病菌。广泛存在于自然环境中、人体皮肤、呼吸道、肠道及医疗器械上。是一种条件致病菌，易发生在免疫力受损的患者身上，尤其在气管插管、气管切开，使用机械通气的病人。主要引起医院获得性肺炎。由于铜绿假单胞菌能通过不同的机制产生对抗菌药物的耐药，导致临床治疗的失败。近年来β-内酰胺类抗生素、免疫抑制剂、抗肿瘤化疗药物的广泛应用，该菌引起的耐药性越来越严重。 铜绿假单胞菌耐药机制主要有：β-内酰胺酶的产生；外膜通透性下降；外膜蛋白OprD₂的缺失引起对亚胺培南的耐药；外膜上存在着特异的药物主动外排系统；氨基糖苷类钝化酶的产生；靶位改变；细菌生物被膜形成。其中产生β-内酰胺酶是铜绿假单胞菌对β-内酰胺类抗生素耐药的主要原因。随着新的β-内酰胺类抗生素应用于临床，细菌也产生了多种β-内酰胺酶，如超广谱β-内酰胺酶（ESBLs），质粒介导的AmpC酶，碳青霉烯酶等。其中β-内酰胺酶的产生是临床常见的细菌耐药的主要原因。 为了解铜绿假单胞菌引起的医院感染特点、所产β-内酰胺酶的类型及耐药情浙江大学2004届硕士学位论文况本实验收集分析了53株铜绿假单胞菌，对这53例铜绿假单胞菌进行耐药性分析并对相关病历进行回顾性分析，对临床铜绿假单胞菌感染及耐药性进行了初步研究。二、材料与方法攻集浙江大学医学院附属第一医院（浙一医院）2003年了月一2003年12月临床标本分离的铜绿假单胞菌53株。采用Kirb丫一Bauer纸片法进行药敏检测;超声破碎法提取p一内酞胺酶;改良三维试验法确定p一内酞胺酶表型;用sPsslo.。软件对资料进行统计处理。三、结果1药敏结果53株铜绿假单胞菌对头抱毗肠和美罗培南敏感性最高，均为79.2%;其次为头抱呱酮/舒巴坦、头抱他陡、阿米卡星、亚胺培南、呱拉西林/三哇巴坦、替卡西林/克拉维酸，敏感率在70%以上;而对喳诺酮类（环丙沙星、左氧氟沙星、莫西沙星），单环内酞胺类（氨曲南），头霉素（拉氧头抱）的耐药及中介率达到了35.8%一77.4%。2.三维试验结果53株铜绿假单胞菌中产碳青霉烯酶8株，占15.1%，产肠pC酶6株，占n.3ryo，有l株可能同时产AmpC酶和ESBLs。3.SPSSIO.0分析产酶组与不产酶组敏感率差异14株产酶细菌同其余39株不产酶细菌的药物敏感率结果显示产酶组细菌的敏感率均低于不产酶组，有H种药物具有显著性差异。表明铜绿假单胞菌中由于碳青霉烯酶和AmpC酶的产生，使得产酶组的细菌耐药性大大增加。浙江大学2004届硕士学位论文四、结论铜绿假单胞菌在医院引起的感染以呼吸道感染为主。，铜绿假单胞菌对喳诺酮类、单环内酞胺类、头霉素类抗生素耐药性较高;对头抱毗肪和美罗培南敏感性最高，可作为临床治疗铜绿假单胞菌感染的选择用药。53株铜绿假单胞菌中所产卜内酞胺酶主要是碳青霉烯酶和AmpC酶。更多还原

【Abstract】 1. BackgroundPseudomonas aeruginosa,also called "pseudomonas pyocyanea",is a common pathogen of nosocomial infection .It can be found in natural enviroment,skin of human body, respiratory tract, intestinal tract and medical instrumentations.It is an important opportunistic nosocomial pathogen and particularly important in hospital acquired pneumoniae,especially in immune-compromised patients and those with tracheal cannula,tracheotomy or mechanical ventilation.With the drug resistance by different mechanisms,it often caused the failure of the clinical treatment.However, the situations of resistance caused by P.aeruginosa become more serious as -lactams, immuno-suppressive drugs and anti-neoplasm drugs are used widely in clinical oractice.Mechanisms of P.aeruginosa drug resistance includerproduction of -lactamases;imipenem resistant by the loss of outer membran porin OprD2;active efflux pumps in outer membran;productions of aminoglycoside-modifying enzymes; the change of target positions;biofilm formation.The production of -lactamases is the main reasoncaused the (3-lactams resistance. The (3-lactamases emerged such as ESBLs. plasmid-induced AmpC,cabapenemases with the new p-lactams in practice.We carried out this study to demonstrate the resistance pattern,the types of P-lactamases and drug resistance of P.aeruginosa. Meanwhile.analyze the cases by-retrospective studies. 2.Materials and methodsThe 53 P.aeruginosa collected from clinical specimens in the Fisrt Affliated Hospital,College of Medicine, Zhejiang University from July to December in 2003. .Antimicrobial activity to the strains were determined by K-B test;extract the p-lactamases by ultrasound; (3-lactamases produced by these strains were characterized by three-dimensional test;SPSS10.0 analyze the data. 3.ResuItsThe most active agents against these strains were cefepime and meropenem with the susceptibility rate of 79.2%;cefoperazone/sulbactam,ceftazidime,amikacin,imipenem,ti-carcillin/clavulanic acid with the susceptibility rate above 70%.The intermediate and resistance rate of quinolones(ciprofloxacin, Levofloxacin,moxifloxin),monobactam(aztreo-nam) and cephamycin(latamoxef) is 35.8-77.4%.Three-dimensional test detected 8 strains with production of carbapenemases and 6 strains with AmpC,l strain probably both ESBLs and AmpC.With SPSS 10.0 to analyze the lactamase-producing strains between non lactainase-producing strains,we found the notable significance in 11 drugs.4.conclusion(1).The infections caused by P.aeruginosa in hospital usually occurred in respiratory-tract.(2).These strains were resistant to quinolones,monobactam and cephamycin;but more susceptible to cefepime and meropenem which can be used in clinical treatment.(3).The main types of 3-lactamases produced by the strains were carbapenemases and AmpC.更多还原