复杂性腹腔感染处理毛恩强

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,*,*,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,*,*,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,*,*,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,*,*,复杂性腹腔感染处理毛恩强,复杂性腹腔内感染,复杂性腹腔内感染,：腹腔内脏器或后腹膜的某一处感染扩散至一个或以上的生理腔隙内，并引起腹膜炎和,/,或脓肿,有原发的感染灶,发生扩散，继发,细菌种类复杂,出现在原发与继发,性腹膜炎治疗失败后的复发性腹膜炎,或持续性腹膜炎，即第三型腹膜炎,化脓性胆囊炎,ACST/,肝脓肿,肠瘘,腹膜炎,化脓性阑尾炎,腹腔多发脓肿,阴道直肠瘘,重症急性胰腺炎,常见疾病与状态,肝胆系统,ACST,：尤其是伴有胆漏,胆漏：胆道相关手术、,Child,手术、肝破裂、肝移植,胆囊坏疽或穿孔：,肝脓肿：腹腔渗液或血源性播散,胃肠道,食道漏：食道与胃或空肠的吻合口漏,胃漏：创伤或炎症引起,十二指肠漏：医源性或感染引起,小肠漏：造瘘口漏,结肠漏：感染或,IBD,阴道直肠瘘：手术损伤,肠间脓肿：引流不畅致残余感染期,胰腺相关感染,重症胰腺炎后腹膜后感染,坏死组织感染,消化道漏：胰漏、胆漏、肠漏、胃漏,残余感染,Clinical Infectious Diseases 2010; 50:13364,复杂性腹腔内感染常见微生物,病原菌,患者,%,（,n=1237,）,兼性需氧革兰阴性菌,大肠埃希菌,71,克雷伯菌属,14,铜绿假单胞菌,14,奇异变形杆菌,5,肠杆菌科,5,厌氧菌,脆弱拟杆菌,35,其他拟杆菌属,71,梭菌属,29,普雷沃登菌属,12,消化链球菌属,17,梭杆菌属,9,真杆菌属,17,革兰阳性需氧菌,链球菌属,38,粪肠球菌,12,屎肠球菌,3,肠球菌属,8,金黄色葡萄球菌,4,1237,例腹腔内微生物学确诊的感染,复杂腹腔感染的治疗,外科引流,抗生素,经验性,降阶梯,停止抗生素应用的指征,Sepsis,处理,外科引流,基础的治疗,原则上外科感染需行引流,(SAP,例外,),耐药菌源于引流推迟,引流,(Operation and/or MID),指征,消化道漏,难以控制的,Sepsis,强化治疗,48,小时仍不能控制的感染,抗生素广覆盖或目标性治疗：,G,-,、,G,+,、抗真菌,纠正贫血，,Hb80g/l,纠正低蛋白血症，,30g/l,负水平衡，消除第三间隙的液体,引流的方法选择,开腹引流：消化道漏、无法穿刺引流的感染灶,微创引流,包裹良好且具体表较近,残余感染难以施行手术,急性肾衰病人推迟手术,急诊或亚急诊外科引流感染灶,术前腹部增强,CT“,行军地图”,一旦怀疑外科感染，应积极诊断，果断处理,留置三腔或双腔引流管,主动引流,留置空肠营养途径，如空肠造瘘、鼻空肠管等,外科引流对脏器的影响,手术导致毒素扩散，大量吸收,中毒性休克,心肌损伤：心脏骤停,呼吸：,ARDS,肾脏：,Septic ARF,DIC,防止脏器损伤的措施,充分引流感染灶，但不过度,“无毒素”手术,“,DCS,”,手术理念,术中可给予糖皮质激素,抗生素的选择与应用策略,抗生素,宿主,细菌,临床转归,微生物学,(,原发疾病及状态,),细菌,耐药性,药代动力学,ADME,给药方案,药效学,抗菌谱,PK/PD,杀菌剂,/,抑菌剂,PAE(Postantibiotic Effects,),联合,临床疗效,细菌清除,患者依从性,耐受性,费用,/,效益,不良反应,宿主,免疫力,植入物,肝肾功能,初始治疗,手术,2004,年全球,IAI,s,病原菌监测,肠杆菌科占占整个革兰阴性杆菌的,86%,Rossi F, Baquero F, Hsueh PR, et al. In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends).J Antimicrob Chemother. 2006;58(1):205-10.,肠杆菌科是,IAIs,最常见的革兰阴性病原菌,n=6156,20022004,年亚太地区,IAIs,病原菌监测,Po-Ren Hsueh, Peter Michael Hawkey. Consensus statement on antimicrobial therapy of intra-abdominal infections in Asia. International Journal of Antimicrobial Agents 30 (2007) 129133.,肠杆菌科占整个分离菌的,82%,(983/1198),铜绿假单胞菌占,9%,(108/1198),与全球的分布趋势相似,肠杆菌科依然是,IAIs,最常见的感染病原菌,占分离菌的百分比,(%),复杂性腹腔内感染的常用抗生素,World Journal of Emergency Surgery 2013, 8:3,对金葡菌的体外抗菌活性比较,Diagnostic Microbiology and Infectious Disease 75 (2013) 331336,产,ESBL,大肠埃希菌,MIC (mg/L),比例,N,50,90,Range,S,I,R,阿米卡星,870,4,32,0.5 to 128,89.7,5.1,5.3,阿莫西林,/,克拉维酸,870,16,32,0.25 to 64,21.1,42.5,36.3,头孢吡肟,870,32,64,0.5 to 64,28.2,14.3,57.6,头孢他啶,870,16,64,1 to 64,-,-,65.5,头孢曲松,870,128,128,0.06 to 128,1.1,2.0,96.9,亚胺培南,143,0.25,0.5,0.06 to 8,97.9,0.7,1.4,左氧氟沙星,870,16,16,0.015 to 16,11.5,3.4,85.1,美罗培南,727,0.06,0.12,0.06 to 32,96.4,1.2,2.3,米诺环素,870,4,32,0.5 to 32,52.3,14.6,33.1,哌拉西林,/,他唑巴坦,870,8,64,0.06 to 256,73.9,16.1,10.0,替加环素,870,0.25,0.5,0.008 to 4,99.8,0.2,0.0,对产,ESBL,大肠埃希菌的体外抗菌活性比较,Ann Clin Microbiol Antimicrob. 2012; 11: 29,肠杆菌属,MIC (mg/L),比例,N,50,90,Range,S,I,R,阿米卡星,2804,2,32,0.5 to 128,89.2,4.4,6.5,阿莫西林,/,克拉维酸,2804,64,64,0.12 to 64,4.7,3.0,92.3,头孢吡肟,2804,0.5,64,0.5 to 64,81.4,4.6,14.1,头孢他啶,2804,8,64,1 to 64,-,-,40.5,头孢曲松,2804,1,128,0.06 to 128,51.9,2.6,45.5,亚胺培南,493,0.5,1,0.06 to 32,95.9,2.6,1.4,左氧氟沙星,2804,0.12,16,0.008 to 16,78.2,3.1,18.8,美罗培南,2311,0.06,0.5,0.06 to 32,94.3,1.9,3.8,米诺环素,2804,4,32,0.5 to 32,61.9,17.7,20.3,哌拉西林,/,他唑巴坦,2804,4,256,0.06 to 256,70.1,11.7,18.1,替加环素,2804,0.5,2,0.008 to 32,96.0,3.5,0.5,对肠杆菌属的体外抗菌活性比较,Ann Clin Microbiol Antimicrob. 2012; 11: 29,鲍曼不动杆菌,MIC (mg/L),比例,N,50,90,Range,S,I,R,阿米卡星,1806,64,128,0.5 to 128,30.4,12.0,57.6,头孢吡肟,1806,32,64,0.5 to 64,25.3,14.4,60.3,头孢他啶,1806,64,64,1 to 64,18.5,7.8,73.8,头孢噻肟,1806,128,128,0.06 to 128,10.5,11.1,78.4,亚胺培南,307,2,32,0.06 to 32,62.5,3.9,33.6,左氧氟沙星,1806,8,16,0.008 to 16,20.9,11.4,67.8,美罗培南,1499,32,32,0.06 to 32,33.9,5.5,60.6,米诺环素,1806,0.5,8,0.5 to 32,89.4,4.6,6.0,哌拉西林,/,他唑巴坦,1806,256,256,0.06 to 256,18.7,9.1,72.2,替加环素,1806,0.5,2,0.008 to 32,-,-,-,对鲍曼不动杆菌的体外抗菌活性比较,Ann Clin Microbiol Antimicrob. 2012; 11: 29,替加环素及对照药治疗不同感染的病死率,Diagnostic Microbiology and Infectious Disease 75 (2013) 331336,单药治疗的广谱或超广谱抗菌谱,抗生素,革兰阴性,革兰阳性,耐药革兰阴性,耐药革兰阳性,厌氧菌,铜绿假单胞菌,内酰胺类,/,内酰胺酶抑制剂合剂,3,代头孢,替加环素,糖肽类,碳青霉烯类,喹诺酮类,同一类中根据产物变化,具有体外活性,没有体外活性,替加环素治疗复杂性腹腔内感染的,PK/PD,独立变量,评价值,偏倚率,(95% CI),P,体重, 94 kg,1.849,6.35 (1.25, 32.4),0.026,基线培养未发现铜绿假单胞菌,2.317,10.1 (1.43, 72.0),0.021,APACHE II,评分, q12h,Vss = 639 L,明显的组织摄取,静脉用药物,80%,通过胆道排泄,.,稳态血药浓度,1,10,0,2,4,6,8,10,12,给药后时间,(hr),血药浓度,log,值,(g/mL),替加环素药代动力学特性,Tygacil package insert. Wyeth,Pharmaceuticals,; 2004.,多重耐药,(MDR),肠杆菌科泛滥！,在我国，,“,ESKAPE”,多重耐药菌株检出率高，,G,-,菌以产,ESBL,菌株为主,7,*,在,G,-,菌中的检出率,#,可分型万古霉素耐药肠球菌在粪肠球菌和屎肠球菌中的检出率,6723/42415,2011,年的世界卫生日主题,抵御耐药性,6,在全球范围内，,“,ESKAPE”,耐药已成为导致患者发病及死亡的重要原,因,5,7.,胡付品等,.,中国感染与化疗杂志,.2012;12(5):321-329.,多重耐药菌,检出率,(%),ESBL (+),大肠埃希菌,50.7,MRSA,50.6,ESBL (+),肺炎克雷伯菌,38.5,不动杆菌属,*,15.9,铜绿假单胞菌,14.2,万古霉素耐药肠球菌,#,1.4,KPC,：耐碳青霉烯类抗生素的肺炎克雷伯杆菌,复杂腹腔感染病人的抗生素应用,初始经验治疗,充分外科引流后,残余感染或引流不畅,停止指征,初始经验治疗,G,-,细菌更为多见：消化道穿孔、胆漏,G,+,细菌：除胆漏或胆道感染外，早期一般不选择,真菌不予考虑,重症胰腺炎：广谱,G,-,细菌、,G,+,细菌的抗生素,充分外科引流后,术后,3-5,天继续术前抗生素,抗生素调整,根据术中微生物依据尽快降低抗生素级别,无微生物依据的病人，经验性降低抗生素级别,残余感染或引流不畅,营养不良、广谱抗生素长期应用、免疫低下,MDR,和,PDR,细菌大量繁殖,非发酵，铜绿、鲍曼、嗜麦芽,发酵肠杆菌，肺克,特治星和替加环素首选,腹腔内感染治疗指南,患者情况,推荐的抗菌治疗,CA,胆道外,稳定,无,ESBL,（,+,）菌感染的危险因素,阿莫西林,/,克拉维酸，或环丙沙星,+,甲硝唑,CA,胆道外,稳定,存在,ESBL,（,+,）菌感染的危险因素,厄他培南或,替加环素,CA,胆道外,危重,无,ESBL,（,+,）菌感染的危险因素,哌拉西林,/,他唑巴坦,CA,胆道外,危重,存在,ESBL,（,+,）菌感染的危险因素,美罗培南或亚胺培南,+/-,氟喹诺酮类,CA,胆道,稳定,无,ESBL,（,+,）菌感染的危险因素,阿莫西林,/,克拉维酸，或环丙沙星,+,甲硝唑,CA,胆道,稳定,存在,ESBL,（,+,）菌感染的危险因素,替加环素,CA,胆道,危重,无,ESBL,（,+,）菌感染的危险因素,哌拉西林,/,他唑巴坦,CA,胆道,危重,存在,ESBL,（,+,）菌感染的危险因素,美罗培南或亚胺培南,+/-,氟喹诺酮类,稳定的医院获得性腹腔内感染,哌拉西林,+,替加环素,+,氟喹诺酮类,危重的医院获得性腹腔内感染,哌拉西林,+,替加环素,+,棘白菌素，或美罗培南或亚胺培 南或多利培南,+,替考拉宁,+,棘白菌素,World Journal of Emergency Surgery 2013, 8:3,2010 IDSA,复杂腹腔感染指南,12,2013 WSES,腹腔感染指南,1,12.,Solomkin JS, et al. Clinical Infectious Diseases. 2010; 50:13364.,1. Sartelli M, et al. World Journal of Emergency Surgery. 2013, 8:3.,国际腹腔感染指南建议,:,应基于严重度,和,/,或,MDR,感染危险因素分级治疗,碳青霉烯类,+,替加环素,替加环素,+SMZ,WBC,、,PCT,、,CRP,逐渐降至正常，,1,周时间,舒普深,+,替加环素,停止抗生素指征,SIRS,消失,【,必需具备,】,PCT+CRP+LPS,均恢复正常,有效外科引流和,/,或感染灶包裹完整,肠道营养恢复,同时满足,+,，最好满足,抗生素,细菌,宿主,耐药性,杀菌剂,感染,免疫,不良反应,药效学,Sepsis,的处理,体液分布,脏器功能保护,抗凝,机械通气,肠道与营养,肝、肾、心,THANKS,谢谢观赏,