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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530%ICU患者感染的患病率约为1850%较普通患者高318倍ICU床位=医院总床位数的5%医院获得性感染=25%Spencer RC. Epidemiology of infection in ICUs. Intensive Care Med 1994; 20: S2-6.Bates DW, Miller EB, Cullen DJ, et al. Patient risk factors for adverse drug events in hospitalized patients. ADE Prevention Study G
2、roup. Arch Intern Med 1999; 159: 2553-60.Singh N, Yu VL. Rational empiric antibiotic prescription in the ICU. Chest 2000; 117: 1496-9.ICU危重病患者的感染EuropeanPrevalenceofInfectioninIntensiveCareStudy(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EPIC内科外科ICUNNISPUMC下呼吸道感染2418652753泌尿系感染4331182
3、05手术部位感染1112916血行性感染151022112其他1830132014感染对患者预后的影响增加住院日额外医疗费用手术部位感染7.33,152肺炎5.95,683血行性感染7.43,517泌尿系感染1.0680总计4.02,100ICU感染的致病菌耐药菌耐药菌NNIS (1996 2000)北京协和医院北京协和医院ICU(1995 2000)平均耐药率平均耐药率 (%)10%百分百分位数位数90%百分百分位数位数MRSA46.515.466.787MRSE74.956.986.795亚胺培南耐药的铜绿假单胞菌16.70.031.327头孢他啶耐药的铜绿假单胞菌11.70.025.02
4、8哌拉西林耐药的铜绿假单胞菌15.00.031.638三代头孢菌素耐药的肠杆菌25.910.050.954亚胺培南耐药的肠杆菌0.90.04.05三代头孢菌素耐药的肺炎克氏菌5.40.018.522三代头孢菌素耐药的大肠杆菌0.90.06.517氟喹诺酮耐药的大肠杆菌4.20.011.1671.Du B, Chen DC, Liu DW, Xu YC, Xie XL, Chen MJ. Natl Med J China 1996; 76: 262-6.2.Li Y, Du B, Chen DC, Liu DW. Beijing Med J 2002; 24: 3-53.Du B. Natl M
5、ed J China 2001; 81: 1278-800%20%40%60%80%100%Luna, 1997Ibrahim, 2000Kollef, 1998Kollef, 1999Rello, 1997Alvarez-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. Intensive 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
6、: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OR = 4.701P = 0.016Bin Du, Yun Long, Hongzhong Liu, Dechang Chen, Dawei Liu, Yingchun Xu, Xiuli Xie. Extended-spectr
7、um beta-lactamase-producing-Escherichia coli and Klebsiella pneumoniae bloodstream infection: risk factors and clinical outcome. Intensive Care Med 2002; 28(12): 1718-23 7/1414/71ICU感染的抗生素治疗:指征经验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
8、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名患者名患者抗生素治疗前抗生素治疗前抗生素治疗过程中抗生素治疗过程中开始抗生素治疗开始抗生素治疗83名患者名患者(60%)血培养阴性或血培养阴性或分离出污染菌分离出污染菌0/83 (0%)分离到致病菌分离到致病菌56名患者名患者(40%)分离到致病菌分离到致病菌26/56 (45%)分离到致病菌分离到致病菌25名患者名患者(45%)分离到致分离到致病的葡萄球菌病的葡萄球菌19/25 (76%)分离到葡萄球菌分离到葡萄球菌14名患者名患者(25%)分离到致分离到致病的链球菌病的链球菌5/14 (36%)分离到链球菌分离到链球菌17名
9、患者名患者(30%)分离到革分离到革兰阴性杆菌兰阴性杆菌2/17 (12%)分离到革兰阴性杆菌分离到革兰阴性杆菌1/139 (0.72%)分离到新的致病菌分离到新的致病菌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
10、血培养的结果,可以根据应用抗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
11、第1组(n=19) 最初抗生素治疗无更改第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-Sou
12、za 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. The impact of changes in antimicrobial therapy on patients with ventilator-associated pn
13、eumonia. Chest 2003; 124(Suppl 4): 79S医院获得性肺炎的抗生素治疗P = 0.004P = 0.04Kawabata 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
14、(104cfu/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: 1353-1357TA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%肺炎患者培养阴性比例18%特异性=033%非肺炎患者培养阴性比例033%非肺炎患者培养阳性比例67100%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，
15、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(72h)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. Significance of the isolation of Candida species from respiratory samples in critically ill, non-neut
16、ropenic 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
17、 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: 583-590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
18、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 postmortem histologic study. Am J Respir Crit Care Med 1997; 156: 583-590ICU感染的诊断微生物学检查结果
19、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 units: a pharmaco-epidemiological multicentre study. Antimicrob Chemother. 2004 J
20、ul;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 impact on the outcome. Crit Care Med. 2003 Feb;31(2):462-7感染性休克的抗生素治疗抗生素治疗的改变(
21、第3 4天)患者数(n = 81), %改变最初的经验性抗生素56 (80)换用窄谱-内酰胺抗生素18 (22)停止联合抗生素治疗34 (42)升阶梯13 (16)根据微生物学检查结果6 (7)得到检查结果前临床恶化7 (8.6)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):462-7VAP的经验性抗生素治疗2001 2
22、003年78名疑似VAP患者铜绿假单胞菌 14.8%改用窄谱抗生素(%)致病菌已知35%革兰阳性菌46%革兰阴性菌54%致病菌未知10%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%)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
23、. 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60.417.9岁平均APACHEII评分23.28.7临床怀疑VAP前机械通气时间2.91.9天Kollef, MH, Kollef K. Antibiotic Utilization and Outcomes for Patients With Clinically Suspected Ventilator-Associated Pneumonia and Negative Quantitative BAL Cul
24、ture 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2.10.8天(13天)没有人应用经验性抗生素3天6例患者(5.9%)因继发VAP应用经验性抗生素距离最初BAL及停用经验性抗生素72h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 Pn
25、eumonia 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 Cultu
26、re Results. Chest 128(4): 2706-2713VAP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痰消失PaO2/FiO2250(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
27、-Associated Pneumonia. Chest 2004; 125:17911799VAP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 2004; 125:17911799VAP停用抗生素的策略预后停用抗生素组(n = 150)对照组(n = 140)P值住院病死率48
28、(32.0)52 (37.1)0.357住院日(天)15.7 18.215.4 15.90.865ICU住院日(天)6.8 6.17.0 7.30.798机械通气天数5.4 5.75.7 7.10.649继发感染56 (37.3)46 (32.9)0.425Micek ST, Ward S, Fraser VJ, Kollef MH. A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia. Che
29、st 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.
30、抗生素指南对临床治疗感染的指导NNIS (n = 48)GUIDE (n = 58)HAP次数5661年龄, 岁67.7 9.668.0 11.5基础疾病充血性心力衰竭17 (35)10 (16)*手术后20 (42)10 (17)*诊断HAP时SAPS评分12.9 3.912.6 3.1发生HAP前住院日20.4 16.619.7 28.0ICU住院日15.6 14.96.2 13.2*机械通气天数10.4 11.75.4 13.2*Soo Hoo GW, Wen YE, Nguyen TV, Goetz MB. Impact of Clinical Guidelines in the Ma
31、nagement 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. Chest 2005; 128: 2778-2787.抗生素指南对临床治疗感染的指导NNIS (n = 56)GUIDE (n = 61)亚胺培南10 (18)61
32、 (100)万古霉素25 (45)28 (46)环丙沙星3 (5)23 (38)阿米卡星8 (14)22 (36)头孢噻肟22 (39)0 (0)甲硝唑21 (38)6 (10)头孢他啶11 (20)0 (0)哌拉西林11 (20)0 (0)庆大霉素11 (20)2 (3)氟康唑8 (14)3 (5)克林霉素7 (13)1 (2)Soo Hoo GW, Wen YE, Nguyen TV, Goetz MB. Impact of Clinical Guidelines in the Management of Severe Hospital-Acquired Pneumonia. Chest
33、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NNIS (n = 56)GUIDE (n = 61)正确的经验性抗生素治疗26 (46)52 (81)*不正确的经验性抗生素治疗309耐药革兰阳性菌158耐药革兰阴性菌151预后14天病
34、死率13 (23)5 (8)*30天病死率21 (38)14 (23)住院病死率25 (45)18 (30)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
