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,1,重症感染的抗菌治疗,2,3,IDSA/ATS 2007,关于重症,CAP,的新标准,次要标准,R30bpm,PaO,2,/FiO,2,250,多肺叶浸润,意识模糊,/,定向障碍,BUN20,g/dl,白细胞降低,410,9,/l,血小板降低,10,万,/mm,3,低体温,36,低血压需要积极的液体复苏,主要标准,有创机械通气,脓毒休克需要血管加压素,诊断：符合,3,项次要标准,/1,项主要标准,Clin Infect Dis 2007;44(suppl):S27-72,5,确当,(appropriate),和足够,(adequate),的抗生素治疗可以降低,GNB,感染病死率,Bochud P-Y et al.Intensive Care Med 2001;27:S33-S48.,0.001,49%,(47-51%),28%,(22-32%),0.001,29%,(23-31%),10%,(0-13%),非致死,5,年,)33%,2,最终死亡,(1-5,年,),性疾病,30%,3,迅速致死性疾病,(1,年,)10%,Intensive Care Med 2004,30:580,7,延误恰当抗生素治疗时间,病死率,24,小时后才开始恰当治疗的患者死亡率最高,Marin H.Kollef,Lee E.Morrow,Michael S.Niederman,et al.,Chest 2006;129;1210-1218,小时,死亡率,8,治疗,铜绿假单胞菌,感染的,VAP,充分初始治疗率,单药治疗,联合治疗,p,值,接受治疗人数,67/183,（,36.7%,）,116/183,（,63.3%,）,APACHE II,积分,189.4,1910,=0.2,充分初始治疗率,38/67,（,56.7%,）,105/116,（,90.5%,）,0.0001,医院死亡率,34/67,（,50.7%,）,43/116,（,37.1%,）,=0.09,Jose Garnacho-Montero,Marcio Sa-Borges,et al.Crit Care Med 2007,35(8):1888-1895,(the rate of appropriate,initial antibiotic treatment),对于铜绿假单胞菌感染的,VAP,，联合抗生素治疗可以大大降低不恰当治疗率,10,严重脓毒症,/,脓毒症休克的抗菌治疗,覆盖,GNB,院内感染，粒减免疫抑制，,慢性器官衰竭,覆盖,GPC,MRS,高流行（医院或社区）,静脉导管感染,HAP/VAP,真菌粒减伴发热,抗菌无效的其他免疫抑制感染,长期广谱抗生素治疗,真菌培养阳性,Sepsis hand book 2007,p.123,12,降阶梯策略,:,释义,广谱覆盖以改善结局,减少耐药选择性压力 平衡,不得已而为之,又不得不为 妥协,经验性治疗,靶向治疗 辩证统一,14,如何降阶梯,?,责任病原体诊断明确,靶向治疗,狭义降阶梯,微生物检测,真,阴性,停药,治疗反应很好,短程治疗,其他参考指标,CPIS,PCT,15,Suspected VAP,MRSA?,Pseudomonas?,Acinetobacter?,ESBLs?,Legionella?,Broad Initial Antimicrobial Coverage,Mecrobiology Results?,Cilinical Response?,Longer course if delayed response or NF GNR,Shorter course if good response and non-NF GNR,Narrow antimicrobial coverage based on culture/susceptibility,Discontinue antimicrobial if culture negative,Fig,。,1,。,Schematic representation of the de-escalation strategy for antimicrobial management of ventilator-associated pneumonia.From left to right:Ventilator-associated pneumonia is suspected,16,Resolution of Clinical Parameters,Mean log CFU/mL 95%CI,Days,Leucocyte Count 95%CI,Days,CFU=colony-forming units.,Am J Respir Crit Care Med,.2001;163:1373.,17,Resolution of Clinical Parameters,Highest Temperature 95%CI,Days,PaO,2,/FIO,2,Ratio,95%CI,Days,Am J Respir Crit Care Med.2001;163:1373.,18,Number of Patients With Positive Culture,Initial Organism,0,2,4,6,8,10,12,14,16,0,3,6,9,12,15,Haemophilus influenzae,and,Streptococcus pneumoniae,Staphylococcus aureus,Enterobacteriaceae,Pseudomonas aeruginosa,Days,No.of Patients,Am J Respir Crit Care Med.2001;163:1374.,20,欧洲多中心随机研究,(N=401),VAP,抗生素治疗：,8d Vs 16d,疗程疗效相似；病死率,18.8,Vs 17.2,；复发率,28.9,Vs 26.0,。,而短程治疗组无抗生素组天数多,(13.1 Vs 8.7d,P240,或,ARDS,0,38.5-39.0,1,(PaO,2,/FiO,2,),240,或未证明,ARDS,2,39.0,2,X,线 无浸润,0,白细胞,4.0-11.0 0,弥漫性,(,或片状,)1,(10,9,/dl)11.0,1,局部浸润,2,带状核,500 +1,气管分泌物 无病原菌生长,0,气管分泌物,6,分符合,VAP,诊断,ARRD 1991;143:1121,24,Figure,：,Duration of antibiotic therapy according to CPIS,EUR RESPIR REV2007;16:43,降低肾毒性,中枢毒性,对,-,内酰胺酶稳定性高,对,DHP,I,稳定性高,1.,细菌外膜渗透性强,2.,对革兰阴性菌,(,特别是,铜绿假单胞菌,）抗菌力增强,N,COOH,S,CH,3,H,H,N,O,OH,1,-,甲基,N,+,N,三唑阳离子,三水物,卓越,源于独特结构,CH,3,安信的化学结构,比阿培南对,PA,的短时杀菌优于美罗培南,起效更快，初始杀菌能力强于美罗培南,浓度在,20uM,下，对于铜绿假单胞菌,PAO1,株，在最初的一个小时内，比阿培南使活菌数降低超过,2,个,log,，而美罗培南活菌数数量降低少于,0.5log,。,图,:,碳青霉烯类和头孢类对铜绿假单胞菌,PAO1,初始杀菌活性比较,比阿培南中枢神经系统毒性更少,抽搐,增强效应（静脉注射，小鼠）,CAZ,比阿培南治疗败血症疗效最好,各种碳青霉烯类药物治疗败血症的临床疗效,THE JAPANESE JOURNAL OF ANTIBIOTICS Apr.2004,57-2,135-147,Chemotherapy 2008;54:386,394,TA%:,300 mgQ12H 300 mg Q8H 600 mg Q12H 600 mg Q8H;,0.5 h,静滴,持续静滴,(8 or 12 h)90%;,对于铜绿假单胞菌、流感嗜血杆菌，需要增加剂量和延长滴注时间，比阿培南,300mgQ6h,3h,或,600mg,g8h,，,3h,小时滴注，能获得,TA%90%;,对于以下情况，应该考虑使用碳青霉烯类,晚发,HAP,疑有多药耐药菌感染，包括产,ESBL,和,AmpC,菌,近期曾经住院治疗,居住在疗养院,近期使用过抗生素,具有感染多药耐药菌的危险因素,以往抗生素治疗失败,碳青霉烯类的应用：一线,or,二线？,Marin H Kollef.Appropriate Empiric Antimicrobial Therapy of Nosocomial Pneumonia:The Role of the Carbapenems.Respiratory Care,2004,49(12):1530-1541,