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1、ICU感染的治疗,ICU感染:患病率,医院获得性感染的患病率为5 30%ICU患者感染的患病率约为18 50%较普通患者高3 18倍ICU床位=医院总床位数的5%医院获得性感染=25%,ICU危重病患者的感染,European Prevalence of Infectionin Intensive Care Study(EPIC)1992年4月29日进行1417个ICU参加总计9567名ICU患者,ICU危重病患者的感染,ICU感染的组成,感染对患者预后的影响,ICU血行性感染:致病菌,ICU获得性肺炎:致病菌,NNIS,PUMCH,ICU感染的致病菌,Du B,Chen DC,Liu DW,
2、Xu YC,Xie XL,Chen MJ.Natl Med J China 1996;76:262-6.Li Y,Du B,Chen DC,Liu DW.Beijing Med J 2002;24:3-5Du B.Natl Med J China 2001;81:1278-80,0%,20%,40%,60%,80%,100,%,Luna,1997,Ibrahim,2000,Kollef,1998,Kollef,1999,Rello,1997,Alvarez-Lerma,1996,最初充分治疗,最初不充分治疗,*病死率指总病死率或感染相关病死率Alvarez-Lerma F et al.Inte
3、nsive Care Med 1996;22:387-394.Rello J et al.Am J Respir Crit Care Med 1997;156:196-200.Kollef MH et al.Chest 1999;115:462-474Kollef MH et al.Chest 1998;113:412-420.Ibrahim EH at al.Chest 2000;118:146-155.Luna CM et al.Chest 1997;111:676-685.,病死率*,ICU中重度感染的危重病患者最初不充分抗生素治疗的病死率*,ESBL阳性菌感染不适当抗生素治疗与病死率,
4、OR=4.701P=0.016,Bin Du,Yun Long,Hongzhong Liu,Dechang Chen,Dawei Liu,Yingchun Xu,Xiuli Xie.Extended-spectrum beta-lactamase-producing-Escherichia coli and Klebsiella pneumoniae bloodstream infection:risk factors and clinical outcome.Intensive Care Med 2002;28(12):1718-23,7/14,14/71,ICU感染的抗生素治疗:指征,经验
5、性抗生素治疗致病菌未知广谱抗生素针对性抗生素治疗(降阶梯治疗)根据致病菌及药敏结果结合临床疗效换用窄谱抗生素,ICU感染的抗生素治疗:意义,经验性抗生素治疗覆盖可能的致病菌降低病死率针对性抗生素治疗(降阶梯治疗)减少广谱抗生素的使用避免耐药发生,抗生素治疗前后血培养的阳性率,139名患者,抗生素治疗前,抗生素治疗过程中,开始抗生素治疗,83名患者(60%)血培养阴性或分离出污染菌,0/83(0%)分离到致病菌,56名患者(40%)分离到致病菌,26/56(45%)分离到致病菌,25名患者(45%)分离到致病的葡萄球菌,19/25(76%)分离到葡萄球菌,14名患者(25%)分离到致病的链球菌,
6、5/14(36%)分离到链球菌,17名患者(30%)分离到革兰阴性杆菌,2/17(12%)分离到革兰阴性杆菌,1/139(0.72%)分离到新的致病菌,Grace CJ,Lieberman J,Pierce K,et al.Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy.Clin Infect Dis 2001;32:1651-5,临床意义,应用抗生素前进行血培养分离到致病菌的可能性增加2.2倍在开始抗生素治疗最初72小时内,连续进行血培养的结果,可以根据应用抗
7、生素前血培养的结果预测极少分离到新的致病菌医生可以等待应用抗生素前的血培养结果回报后,再进行新的血培养,Grace CJ,Lieberman J,Pierce K,et al.Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy.Clin Infect Dis 2001;32:1651-5,医院获得性肺炎的抗生素治疗,目的:评价频繁更换抗生素对VAP患者预后的影响方法:回顾性分析56名VAP患者的临床资料根据更换抗生素的频率分为4组第1组(n=19)最初抗生素治疗无更
8、改第2组(n=8)最初抗生素治疗更改1次第3组(n=19)最初抗生素治疗更改2次第4组(n=10)最初抗生素治疗更改 3次降阶梯治疗及简化治疗除外,Kawabata M,Corla-Souza A,Niederman M,et al.The impact of changes in antimicrobial therapy on patients with ventilator-associated pneumonia.Chest 2003;124(Suppl 4):79S,医院获得性肺炎的抗生素治疗,Kawabata M,Corla-Souza A,Niederman M,et al.Th
9、e impact of changes in antimicrobial therapy on patients with ventilator-associated pneumonia.Chest 2003;124(Suppl 4):79S,医院获得性肺炎的抗生素治疗,Kawabata M,Corla-Souza A,Niederman M,et al.The impact of changes in antimicrobial therapy on patients with ventilator-associated pneumonia.Chest 2003;124(Suppl 4):7
10、9S,医院获得性肺炎的抗生素治疗,P=0.004,P=0.04,Kawabata M,Corla-Souza A,Niederman M,et al.The impact of changes in antimicrobial therapy on patients with ventilator-associated pneumonia.Chest 2003;124(Suppl 4):79S,如何鉴别真正的致病菌和污染菌,常见致病菌(95%)金黄色葡萄球菌大肠杆菌肠杆菌铜绿假单胞菌肺炎链球菌白色念珠菌,常见污染菌(5%)棒状杆菌属芽孢杆菌属疮疱丙酸杆菌,Towns ML,Quartey SM
11、,Weinstein MP,et al.The clinical significance of positive blood cultures:a prospective,multicenter evaluation,abstr.C-232.In Abstracts of the 93rd General Meeting of the American Society for Microbiology 1993.American Society for Microbiology,Washington,D.C.Weinstein MP,Towns ML,Quartey SM,et al.The
12、 clinical significance of positive blood cultures in the 1990s:a prospective comprehensive evaluation of the microbiology,epidemiology,and outcome of bacteremia and fungemia in adults.Clin Infect Dis 1997;24:584-602.,鉴别困难的分离株,Towns ML,Quartey SM,Weinstein MP,et al.The clinical significance of positi
13、ve blood cultures:a prospective,multicenter evaluation,abstr.C-232.In Abstracts of the 93rd General Meeting of the American Society for Microbiology 1993.American Society for Microbiology,Washington,D.C.Weinstein MP,Towns ML,Quartey SM,et al.The clinical significance of positive blood cultures in th
14、e 1990s:a prospective comprehensive evaluation of the microbiology,epidemiology,and outcome of bacteremia and fungemia in adults.Clin Infect Dis 1997;24:584-602.,鉴别困难的分离株,Geffers C,Farr BM.Positive predictive value of a percutaneously drawn blood culture growing skin flora varies markedly by organis
15、m.Infect Control Hosp Epidemiol 2005;26(6):507-509,凝固酶阴性葡萄球菌 感染 vs.污染,Beekmann SE,Diekema DJ,Doern GV.Determining the clinical significance of coagulase-negative Staphylococci isolated from blood cultures.Infect Control Hosp Epidemiol 2005;26(6):559-566,长期机械通气患者下呼吸道细菌定植,目的:检查接受长期机械通气患者肺泡内细菌负荷背景:大学医院
16、及长期护理院的呼吸监护病房患者:接受长期机械通气且没有肺炎临床表现的14名患者指标:右中叶及舌叶BALF的定量培养结果:在进行检查的32个肺叶中的29个,至少有一种微生物定量培养 104 cfu/mL.多数肺叶有多种微生物生长,Baram D,Hulse G,Palmer LB.Stable Patients Receiving Prolonged Mechanical Ventilation Have a High Alveolar Burden of Bacteria.Chest 2005;127:1353-1357,TA培养结果与医院获得性肺炎,敏感性=82%肺炎患者培养阳性比例82%肺
17、炎患者培养阴性比例18%特异性=0 33%非肺炎患者培养阴性比例0 33%非肺炎患者培养阳性比例67 100%,TA培养结果与医院获得性肺炎,某些致病菌（如铜绿假单胞菌）培养为阴性时，可以除外其感染,致病菌定植菌,下呼吸道分离出念珠菌的意义,25名非粒细胞缺乏的机械通气(72 h)患者去世后立即进行肺活检去世后立即进行下呼吸道采样气道内吸取物保护性毛刷 PSB肺泡支气管灌洗 BAL盲目活检 平均每例患者14块组织双侧纤维支气管镜指导下活检 每例患者2块组织肺组织标本的组织学检查呼吸道标本区分为念珠菌阳性及其他,el Ebiary M,Torres A,Fabregas N,et al.Sign
18、ificance of the isolation of Candida species from respiratory samples in critically ill,non-neutropenic patients:an immediate postmortem histologic study.Am J Respir Crit Care Med 1997;156:583-590,下呼吸道分离出念珠菌的意义,2名患者(8%)明确肺部念珠菌病25名患者375份肺活检标本280份(77%)培养阳性共分离470株细菌10名患者(40%)分离出念珠菌属(n=40,9%)10名患者(40%)1
19、份肺组织活检标本分离念珠菌属至少其他一种采样方法也分离到相同的念珠菌不同采样方法进行念珠菌定量培养相关性很好不能鉴别念珠菌肺炎,el Ebiary M,Torres A,Fabregas N,et al.Significance of the isolation of Candida species from respiratory samples in critically ill,non-neutropenic patients:an immediate postmortem histologic study.Am J Respir Crit Care Med 1997;156:583-5
20、90,下呼吸道分离出念珠菌的意义,结论在接受机械通气的非粒细胞缺乏的危重病患者肺组织活检分离到念珠菌的比例高达40%明确的念珠菌肺炎仅为8%肺组织的不同区域普遍存在念珠菌定植呼吸道标本中分离到念珠菌,不能准确预测是否存在念珠菌肺炎无论是否进行定量培养,el Ebiary M,Torres A,Fabregas N,et al.Significance of the isolation of Candida species from respiratory samples in critically ill,non-neutropenic patients:an immediate postmo
21、rtem histologic study.Am J Respir Crit Care Med 1997;156:583-590,ICU感染的诊断,微生物学检查结果不能取代临床诊断VAP:下呼吸道标本的培养结果用于调整抗生素治疗非诊断肺炎,ICU患者的抗生素治疗,意大利43个ICU共979名危重病患者(14岁)99%全身性感染患者应用抗生素经验性广谱抗生素93%抗生素药敏结果93%经验性抗生素治疗错误37.6%更换或加用抗生素降阶梯治疗(n=16),Malacarne P,Rossi C,Bertolini G,et al.Antibiotic usage in intensive care
22、units:a pharmaco-epidemiological multicentre study.Antimicrob Chemother.2004 Jul;54(1):221-4,感染性休克的抗生素治疗,107名感染性休克患者细菌学证实78(72%)经验性抗生素治疗-内酰胺+氨基糖甙n=59-内酰胺+氟喹诺酮n=21加用万古霉素n=14正确的经验性抗生素治疗89%(69/78),Leone M,Bourgoin A,Cambon S,et al.Empirical antimicrobial therapy of septic shock patients:adequacy and im
23、pact on the outcome.Crit Care Med.2003 Feb;31(2):462-7,感染性休克的抗生素治疗,Leone M,Bourgoin A,Cambon S,et al.Empirical antimicrobial therapy of septic shock patients:adequacy and impact on the outcome.Crit Care Med.2003 Feb;31(2):462-7,VAP的经验性抗生素治疗,CAP的经验性抗生素治疗,204名住ICU的重症CAP患者致病菌已知117(57.3%)更换抗生素 85(41.6%)
24、换用窄谱抗生素65(31.9%)换用正确抗生素11(5.4%)联合应用抗生素 5(2.4%)铜绿假单胞菌,Rello J,Bodi M,Mariscal D,et al.Microbiological testing and outcome of patients with severe community acquired pneumonia.Chest 2003;123:174-80,经验性抗生素:下呼吸道培养阴性,临床怀疑VAP但BAL培养结果阴性的101名患者19名患者(18.8%)BAL前应用抗生素平均年龄60.4 17.9岁平均APACHE II评分23.2 8.7临床怀疑VAP前
25、机械通气时间2.9 1.9天,Kollef,MH,Kollef K.Antibiotic Utilization and Outcomes for Patients With Clinically Suspected Ventilator-Associated Pneumonia and Negative Quantitative BAL Culture Results.Chest 128(4):2706-2713,经验性抗生素:下呼吸道培养阴性,BAL后65名患者(64.4%)应用经验性抗生素疗程2.1 0.8天(1 3天)没有人应用经验性抗生素 3天6例患者(5.9%)因继发VAP应用经验
26、性抗生素距离最初BAL及停用经验性抗生素 72 h住院死亡35例(34.7%)包括2例继发VAP患者死亡与VAP无关,Kollef,MH,Kollef K.Antibiotic Utilization and Outcomes for Patients With Clinically Suspected Ventilator-Associated Pneumonia and Negative Quantitative BAL Culture Results.Chest 128(4):2706-2713,经验性抗生素:下呼吸道标本阴性,对于临床怀疑VAP但BAL培养阴性患者72小时内停用经验性抗
27、生素甚至不应用经验性抗生素,Kollef,MH,Kollef K.Antibiotic Utilization and Outcomes for Patients With Clinically Suspected Ventilator-Associated Pneumonia and Negative Quantitative BAL Culture Results.Chest 128(4):2706-2713,VAP停用抗生素的临床指标,确认引起肺部浸润影的非感染性因素(如肺不张,肺水肿)从而无需抗生素治疗症状及体征提示感染得到控制体温 38.3C白细胞计数 25%胸片表现改善或无进展脓性
28、痰消失PaO2/FiO2 250(停用抗生素时须满足所有上述标准),Micek ST,Ward S,Fraser VJ,Kollef MH.A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia.Chest 2004;125:17911799,VAP停用抗生素的策略,Micek ST,Ward S,Fraser VJ,Kollef MH.A Randomized Controlled Trial o
29、f an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia.Chest 2004;125:17911799,VAP停用抗生素的策略,Micek ST,Ward S,Fraser VJ,Kollef MH.A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia.Chest
30、 2004;125:17911799,抗生素指南对临床治疗感染的指导,西洛杉矶医院HAP抗生素指南轻中度HAP哌拉西林/他唑巴坦头孢曲松或左旋氧氟沙星(青霉素过敏)重度HAP亚胺培南+阿米卡星(95%)亚胺培南+环丙沙星(或左旋氧氟沙星)(肾毒性)MRSA:万古霉素非典型病原体:阿奇霉素,Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia.Chest 2005;128:2778-2787.,抗生素指南对
31、临床治疗感染的指导,Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia.Chest 2005;128:2778-2787.,抗生素指南对临床治疗感染的指导,Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia.Ch
32、est 2005;128:2778-2787.,抗生素指南对临床治疗感染的指导,Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia.Chest 2005;128:2778-2787.,抗生素指南对临床治疗感染的指导,Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe
33、Hospital-Acquired Pneumonia.Chest 2005;128:2778-2787.,抗生素指南对临床治疗感染的指导,Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia.Chest 2005;128:2778-2787.,抗生素指南对临床治疗感染的指导,Cox风险比例模型30天病死率(HR)GUIDE0.46(p=.041)住院病死率(HR)GUIDE0.44(p=.018),Soo Hoo GW,Wen YE,Nguyen TV,Goetz MB.Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia.Chest 2005;128:2778-2787.,总结,ICU患者为感染的高危人群适当的经验性抗生素治疗能够改善预后正确理解微生物学检查结果及时调整针对性抗生素治疗,
