院内获得性感染诊治(剪辑后)讲座课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,院内获得性感染的诊治,上海交通大学医学院附属医院,内 容,医院内感染的病原菌及其药敏情况,耐药菌产生的因素,耐药菌感染的治疗,今天不采取行动,明天将无药可用,细菌耐药性,Bad Bugs: ESKAPE,E,nterococcus faecium;,S,taphylococcus aureus;,K,lebsiella;,A,cinetobacter;,P,seudomonas;,E,nterobacter,中国,: ESBL,的发生率,year,2010,年,CHINET,耐药监测革兰阴性菌菌种分布,细菌,株数,细菌,株数,大肠埃希菌,9225,26.91,摩根菌属,195,0.57,克雷伯菌属,5529,16.13,产碱杆菌,107,0.31,不动杆菌属,5523,16.11,少动鞘氨醇单胞菌,94,0.27,铜绿假单胞菌,5080,14.82,金杆菌属,92,0.27,肠杆菌属,1961,5.72,罗尔斯顿菌属,74,0.22,嗜麦芽窄食单胞菌,1661,4.85,气单胞菌属,76,0.22,变形杆菌属,907,2.65,多源菌属,53,0.15,流感嗜血杆菌,734,2.14,普罗威登菌属,46,0.13,沙雷菌属,437,1.27,志贺菌属,149,0.43,其他假单胞菌,420,1.23,丛毛单胞菌,14,0.04,其他嗜血杆菌,395,1.15,奈瑟菌属,11,0.03,沙门菌属,355,1.04,博特菌属,13,0.04,柠檬酸杆菌属,350,1.02,黄杆菌属,16,0.05,伯克霍尔德菌属,320,0.93,其他,218,0.64,莫拉菌属,227,0.66,合计,34282,100.0,院内常见,G,-,菌耐药率排名,2010 CHINET,头孢哌酮,/,舒巴坦,亚胺培南,美罗培南,哌拉西林,/,他唑巴坦,头孢吡肟,头孢他啶,大肠埃希菌属,6.5,1.6,1.4,5.9,25.7,30.7,克雷伯克菌属,14.8,8.8,8.9,16.6,23.8,35.4,柠檬杆菌属,16.7,8.7,7,20.6,17.2,42,变形杆菌属,1.9,5.2,1.6,4.3,4.3,5.7,铜绿假单胞菌,17.9,3,0,.,8,25.8,24.1,19.3,21.6,不动杆菌,30.7,57.1,58.3,64.6,64.1,64.2,嗜麦芽窄食单胞菌,13.8,无抗菌谱,无抗菌谱,无抗菌谱,无抗菌谱,无抗菌谱,肠杆菌科,9.1,4.6,4.2,10.4,22.0,31.0,非发酵菌,23.5,48.7,45.6,42.9,41.6,42.6,绿色表示耐药率,30%,2010,年,14,家医院,9225,株大肠埃希菌耐药率（,%,）,2010,年,14,家医院,5529,株克雷伯菌属耐药率（,%,）,2010,年,14,家医院,13751,株非发酵菌耐药率,（,%,）,抗菌药物,耐药,敏感,头孢哌酮,/,舒巴坦,23.5,54.4,美罗培南,45.6,51.7,阿米卡星,38.1,58.4,头孢他啶,42.6,52.6,头孢吡肟,41.6,52.5,哌拉西林,/,他唑巴坦,42.9,52.8,亚胺培南,48.7,48.4,环丙沙星,43.4,50.5,2010,年,14,家医院,5080,株铜绿假单胞菌耐药率（,%,）,2010,年,14,家医院,5523,株不动杆菌属,(,鲍曼不动,89.6%),细菌的耐药率（,%,）,除头孢哌酮,/,舒巴坦、米诺环素外，其余抗菌药的耐药率均,50%,亚胺培南和美罗培南的耐药率接近,60%,2010,年,14,家医院嗜麦芽窄食单胞菌和伯克霍尔德菌属的耐药率（,%,）,抗菌药物,嗜麦芽窄食单胞菌（,1661,株）,抗菌药物,伯克霍尔德菌属（,320,株）,耐药,敏感,耐药,敏感,头孢哌酮,/,舒巴坦,13.8,65.2,哌拉西林,/,他唑巴坦,22.1,70.4,左氧氟沙星,10.7,86.1,头孢他啶,21.8,72.8,复方磺胺甲噁唑,11.2,86.7,美罗培南,19.7,70.3,米诺环素,3.4,82.1,复方磺胺甲噁唑,27.6,64.0,米诺环素,17.6,68.1,CHINET,各医院,不动杆菌属,对亚胺培南和美罗培南的耐药率,医院,株数,亚胺培南,美罗培南,耐药,敏感,耐药,敏感,上海儿童医院,100,50.0,48.0,48.0,52.0,广州医大一附院,243,33.3,62.9,39.5,58.9,重庆医大一附院,377,63.1,35.8,63.3,35.5,上海儿科医院,186,47.0,43.8,58.9,37.8,卫生部北京医院,247,61.9,38.1,61.5,37.7,上海华山医院,532,62.7,36.7,63.8,36.0,北京协和医院,706,67.5,32.1,68.0,31.7,甘肃省人民医院,244,12.3,87.7,13.2,86.4,上海瑞金医院,503,46.8,53.0,46.1,53.3,湖北同济医院,595,54.8,43.4,57.6,42.1,浙医一附院,782,74.6,24.6,75.7,23.8,新疆医大一附院,294,35.8,61.8,32.2,65.3,安徽医大一附院,422,54.0,43.6,58.4,40.4,昆明医大一附院,292,72.4,24.0,70.4,29.6,ESBLs,（,+,）和,ESBLs,（,-,）肠杆菌科细菌对抗菌药物敏感率和耐药率（上海,2008,）,不发酵革兰阴性杆菌对抗菌药物的敏感率和耐药率（上海,2008,）,肠杆菌科细菌和不发酵革兰阴性杆菌对,9,种抗菌药物的敏感率和耐药率（上海,2008,）,各医院分离的泛耐药革兰阴性杆菌的检出率（上海,2008,）,19,上海地区不动杆菌属的耐药性变迁,耐药率,%,嗜麦芽窄食单胞菌临床分离率逐年上升,(,上海,),Wang F, et al. Chin J Infect Chemother.2008.3(2):65-70,MDR,：通常把对常用的,7,种抗假单胞菌的抗生素（包括抗假单胞菌的青霉素类、头孢菌素类、氨基糖苷类、喹诺酮类、碳青霉烯类、四环素类、磺胺类）中的至少,3,类耐药的,AB,菌株称之为多重耐药菌,PDR,：对上述,7,类抗生素全耐药的细菌菌株称之为泛耐药菌。,MDR,或,PDR,引起医院感染影响因素,抗生素压力,携带耐药菌患者的流动,长期住院,机械通气,近期手术,入住,ICU,疾病严重程度,感染控制措施不到位,产,ESBL,的危险因素,Risk factor,OR,95% CI OR,P value,机械通气天数,1.1,1.06-1.15,0.001,三代头孢菌素,7.17,2.59-19.8,0.001,氨基糖苷类,2.65,1.15- 6.09,0.02,SXT,8.84,3.07-25.5,0.001,ARDS,3.1,1.0-9.7,0.05,23,Journal of Antimicrobial Chemotherapy 2005 56(1):139-145,Figure 1.,Annual consumption (g/patient-day x 1,000) of carbapenems, extended-spectrum cephalosporins, ciprofloxacin, aminoglycosides and % of isolates of imipenem-resistant and PDRAB at the National Taiwan University Hospital, 19932000.,Hsueh PR,et al. Emerg Infect Dis. 2002 8(8):827-832.,产,ESBLs,菌株,产生,与,三代头孢,相关,三代头孢菌素与,ESBLs,菌株产生增加具有明显相关性,，在中国绝大多是为,CTX-M,型，主要以头孢曲松以及头孢噻肟的过度使用有关,Paterson DL,et al. Ann Intern Med. 2004 Jan 6;140(1):26-32.,三代,头孢菌素,产,ESBLs,菌株,(n=78),非产,ESBLs,菌株,(n=175),风险率,头孢噻肟,33.3,66.7,1.1,头孢曲松,85.7,14.3,3.31,头孢他啶,66.7,33.3,2.26,任何三代头孢,75.2,25.8,2.99,亚胺培南与,MDR,铜绿假单胞菌（,MDRP,）的相关性,P,值,OR,值,OR,的,95%,可信区间,年龄（岁）,0.374,1.010,0.981.05,ICU/RCU,0.56,0.657,0.162.70,COPD/,支扩,0.182,2.96,0.60214.56,APACHE II,0.977,1.001,0.9161.095,机械通气,0.010,8.19,1.6540.7,HAP,0.731,1.292,0.35.56,混合感染,0.306,2.035,0.5222.936,氟喹喏酮,0.188,2.749,0.6112.4,亚胺培南,/,美罗培南,0.0001,44,8,9,16219,曹彬 王辉 朱元珏 陈民钧,.,中华呼吸结核杂志，,2004,年,1,月底,27,卷第,1,期，,P31-35.,采用病例对照研究方法，收集北京协和医院,1999,年,1,月,-2002,年,12,月,MDRP,引起的院内感染,44,例，并随机选择同时期敏感铜绿假单胞菌院内感染,68,例作为对照，采用单因素及多因素,logistic,回归进行分析,独立危险因素,亚胺培南消耗量与铜绿假单胞菌耐药的相关性,Lepper PM, et al.,Antimicrob Agents Chemother,. 2002;46:2920-2925.,在头孢他啶，哌拉西林,/,他唑巴坦与亚胺培南三种药物中，唯有亚胺培南的使用与铜绿假单胞菌的耐药呈显著相关。,铜绿假单胞菌对亚胺培南耐药显著相关，同时与铜绿假单胞菌对头孢他啶和哌拉西林,/,他唑巴坦耐药呈显著相关。,结论：,-,内酰胺酶复合制剂替换三代头孢菌素和亚胺培南,可降低产,ESBLs,菌株的检出率,Pena, et al. Antimocrob Agents Chemother 1998; 42:53-8,注：,93,年,9,月减少三代头孢菌素使用增加亚胺培南的使用,94,年,1,月哌拉西林,/,他唑巴坦加入干预，与亚胺培南同时使用,94,年,5,月开始增加哌拉西林,/,他唑巴坦用量，同时减少亚胺培南和三代头孢菌素使用后，,ESBLs,发生率才开始明显下降,西班牙巴塞罗那,Bellvitge,医院的抗生素干预研究,- 200,- 150,- 100,- 50,- 0,DDD/1000,患者,-,天,93 93 93 94 94 94 95 95 95,1-4,月,5-8,月,9-12,月,1-4,月,5-8,月,9-12,月,1-4,月,5-8,月,9-12,月,事件发生例数,/1000,患者,-,天,10 -,8 -,6 -,4 -,2 -,0 -,不产,ESBLs-KP,产,ESBLs-KP,DDD,MDR,不动杆菌的产生与碳青霉烯类相关,随着碳青霉烯类药物应用的减少，鲍曼不动杆菌的检出率下降，但所检出的鲍曼不动杆菌绝大多数都对碳青霉烯类药物耐药,Xavier Corbella et al. J Clin Microbiol.,2000 November; 38(11): 40864095.,- 14,- 12,- 10,- 8,- 6,- 4,- 2,- 0,DDD,碳青霉烯类,/100ICU,患者,-,天,事件发生例数,/100ICU,患者,35 -,30 -,25 -,20 -,15 -,10 -,5 -,0 -,干预,CS-,鲍曼不动杆菌,CR-,鲍曼不动杆菌,碳青霉烯类使用,第一阶段,第二阶段,第三阶段,非发酵菌等细菌耐药性的生化机制,灭活酶或钝化酶的产生（如,内酰胺酶）,渗透屏障的作用：细菌细胞壁或细胞膜通透性的下降，使抗菌药无法进入细胞内,主动外排机制：细菌能依靠主动外排泵出机制来减少细菌内药物浓度,作用靶位改变,细菌生物膜的形成,有人发现,Acinetobacter baylyi,ADP1,拥有比大肠杆菌感受态细胞强大,100,倍的捕获外源,DNA,能力；错配修复系统,mutS,的缺失增加了部分不动杆菌的突变频率。,注：,Adams MD, Goglin K, Molyneaux N, er al.,Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii.,J Bacteriol. 2008 Dec;190(24):8053-64.,鲍曼不动杆菌治疗选择,含舒巴坦制剂（,头孢哌酮,/,舒巴坦、氨苄西林,/,舒巴坦,）,碳青霉烯类,氨基糖苷类,氟喹诺酮类（,环丙沙星,、,左氧氟沙星,）,四环素类（,米诺环素,、,多西环素,）,甘氨酰环素（,替加环素,）,多粘菌素,、,粘菌素,抗假单胞菌青霉素类,抗假单胞菌头孢菌素类,含舒巴坦制剂,舒巴坦直接作用于细菌的青霉素结合蛋白,PBP2,，从而显示出它对不动杆菌的独特杀菌作用。同时它可抑制细菌产生的多种,-,内酰胺酶（,TEM1,、,TEM2,、,SHV1,等）和多数超广谱,-,内酰胺（,ESBLs,），及多种水解酶。,体外试验证实舒巴坦可有效抑制外排机制，可使头孢哌酮对产,AmpC,酶和外排的铜绿假单胞的,MICs,下降,8,倍，可使细菌对头孢哌酮耐药转为敏感。,注：,Fass RJ, Gregory WW, Damato RF, et al. In vitro activities of cefoperazone and sulbactam singly and in combination against cefoperazone-resistant members of the family ecterobacteriaceae and nonfermenters. Antimicrobial agents and chemotherapy,1990,34(11): 2256-2259,舒普深,中的头孢哌酮可快速通过,3,种外膜通道蛋白，对抗细菌耐药,Satake S, Yoshihara E, Nakae T. Diffusion of beta-lactam antibiotics through liposome membranes reconstituted from purified porins of the outer membrane of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1990; 34(5): 685-90,研究中检测的菌株为铜绿假单胞菌,联合治疗,辅助治疗,对于耐药菌的治疗不能只考虑使用抗菌药物，要注意机体抵御感染的能力。,蔡挺等用舒普深联合胸腺肽,1,治疗多重耐药菌感染，取得了较好的疗效提示我们，对多重耐药菌的治疗，在抗感染的同时提高机体的免疫功能可能起到事半功倍的效果。胸腺肽可调节人体细胞免疫功能，,大剂量免疫球蛋白可使体内抗体滴度明显升高,注：蔡挺，陈琳，许小敏，等,.,重症监护病房鲍曼不动杆菌的耐药性及同源性,.,现代实用医学，,2006,，,18,（,4,）：,229-231.,疗程与预后,和敏感菌相比，耐药菌的毒力并不增加，故病死率不一定增加，基础疾病及本次疾病的严重程度将最终影响预后。,器官功能衰竭和白细胞计数增高是与败血症死亡率的独立相关因素。有时往往与细菌的清除和培养前机械通气时间，肺内为单一细菌感染和患者的意识状况有关。,细菌的清除与否并不完全反映临床疗效，避免为获得彻底清除而长期用药，减少因此而引发的更严重的耐药问题。,注：,Yu VL, Chiou CC, Feldman C, et al.,An international prospective study of pneumococcal bacteremia, correlation with in vitro resistance, antibiotics administered and clinical outbreakJ,Clin Infect Dis,2003,37(2):230-237,医院感染的预防,防治,MDR,或,PDR,感染,最好的办法是预防。,医院感染多重,/,泛耐药鲍曼不动杆菌的同源性分析,防止耐药菌在医院内传播的措施,手卫生,标准的预防措施,适当的隔离措施,器械和环境的清洁和消毒,耐药性监测,抗生素管理，必要时有计划地限制使用某一类抗生素,清除气道及伤口的定植菌,1 Segal-maurer US, Rahal JJ, Consideration in control and treatment of nosocomial infections due to multidrug reisistant Acinetobactor Baumanni. Clin Infect Dis,2003,36: 1268-74,2 Losifidis E, Antachopoulos C, Loannidou M. Colostin administration to pediatric and neonatal patients. Eur J Pediatr 2010,(1):1137-1141,