《ICU感染的治疗》PPT课件.ppt

ICU感染的治疗,北京协和医院 杜 斌,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%,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 Group. 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,European Prevalence of Infection in 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, 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: 3-5 Du 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. 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; 115:462-474 Kollef 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,OR = 4.701 P = 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,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. 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 pneumonia. Chest 2003; 124(Suppl 4): 79S,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, 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 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 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 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,Geffers C, Farr BM. Positive predictive value of a percutaneously drawn blood culture growing skin flora varies markedly by organism. 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. 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,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 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: 583-590,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 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 impact 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%) 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 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 of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia. Chest 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.,抗生素指南对临床治疗感染的指导,Soo Hoo GW, Wen YE, Nguyen TV, Goetz MB. Impact of Cl