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1、导管相关性血行性感染(CRBSI)诊断、治疗与预防北京协和医院MICU江伟CRBSI: 流行病学美国ICU每年发生16,000例CRBSI病死率18% (0 35%)每年死亡500 4,000例每例CRBSI医疗费用$28,690 - $56,000每年医疗费用$60,000,000 460,000,000CDC. MMWR 2002; Heiselman JAMA 1994; Dimick Arch Surg 2001CRBSI: 中国 vs. 全球数据INICC中国上海中国上海 2004-2009总体均值总体均值(95%CI)INICC 2004-2009总体均值总体均值(95%CI)US
2、 NHSN 2006-2008总体均值总体均值(95%CI)内科ICUCLABSI4.3 (3.7 5.0)14.7 (13.8 15.6)1.9 (1.8 2.0)外科ICUCLABSI3.5 (3.2 3.7)5.0 (4.7 5.4)2.3 (2.2 2.4)儿科ICUCLABSI3.5 (2.7 4.4)10.7 (9.9 11.5)3.0 (2.8 3.2)Tao L, Hu B, Rosenthal VD, et al. Device-associated infection rates in 398 intensive care units in Shanghai, China:
3、 International Nosocomial Infection Control Consortium (INICC) findings. Int J Infect Dis 2011; 15: e774-e780中国CRBSI数据: 致病菌(n = 845)Tao L, Hu B, Rosenthal VD, et al. Device-associated infection rates in 398 intensive care units in Shanghai, China: International Nosocomial Infection Control Consortiu
4、m (INICC) findings. Int J Infect Dis 2011; 15: e774-e780CRBSI: Changing EpidemiologyMarcos M, Soriano A, Inurrieta A, et al. Changing epidemiology of central venous catheter-related bloodstream infections: increasing prevalence of Gram-negative pathogens. J Antimicrob Chemother 2011; 66: 2119-2125CR
5、BSI: 发病机制CRBSI: 微生物学诊断方法诊断标准诊断标准敏感性敏感性特异性特异性缺点缺点无需拔除无需拔除CVC的方法的方法同时定量血培养经CVC留取血培养菌落计数相当于外周血培养菌落计数的5倍或更多93%97-100%耗费人力，价格昂贵血培养阳性时间差经CVC留取血培养报警时间较外周血培养报警时间提前 2小时89-90%72-87%若经CVC输注抗生素，结果难以解释经CVC留取定量血培养经CVC留取定量血培养 100 CFU/ml81-86%85-96%无法鉴别CRBSI和菌血症吖啶橙白细胞离心涂片发现任何细菌87%94%未得到广泛应用腔内毛刷定量培养 100 CFU/ml95%84%
6、可能导致菌血症，心律失常或栓塞需要拔除需要拔除CVC的方法的方法CVC尖端半定量培养，滚动平板导管尖端 15 CFU/ml45-84%85%无法培养腔内细菌CVC定量培养：离心，混旋，超声振荡导管尖端 103 CFU/ml82-83%89-97%临界值尚不明确CVC革兰染色和吖啶橙染色镜检直接看到微生物84-100%97-100%耗费人力，缺乏实用性Raad I, Hanna H, Maki D. Intravascular catheter-related infections: advances in diagnosis, prevention, and management. Lance
7、t Infect Dis 2007; 7: 645-657CRBSI: 腔外感染的临床表现全身表现发热白细胞增多插管局部表现炎症表现不敏感（多数导管感染并无插管局部炎症表现）不特异（出现相应表现亦无需拔除导管）提示导管感染的症状和体征插管部位脓性分泌物插管部位蜂窝织炎超过4 mmCRBSI: 腔外感染的实验室诊断滚动平板技术（Maki法）*将导管尖端放置在含有5%羊血的Columbia琼脂培养基的平皿上将导管尖端在平皿表面前后滚动至少3 4次 15 CFU/plate外周血培养阳性且与导管尖端培养一致Guembe M, Martin-Rabadan P, Echenagusia A, et a
8、l. How should long-term tunneled central venous catheters be managed in microbiology laboratories in order to provide an accurate diagnosis of colonization? J Clin Microbiol 2012; 50: 1003-1007*even for long-term tunneled central venous catheters, with detection of 94.9% of catheter colonizationCRBS
9、I: 插管部位消毒10%碘仿碘仿(n = 227)70%乙醇乙醇(n = 227)2%氯己啶氯己啶(n = 214)中心静脉插管(n = 77)(n = 32)(n = 67)局部感染(%)15 (19.5)5 (15.6)4 (5.9)菌血症(%)5 (6.5)2 (6.3)1 (1.5)动脉导管(n = 150)(n = 195)(n = 147)局部感染(%)6 (4.0)6 (3.1)1 (0.7)菌血症(%)1 (0.7)1 (0.5)0总计(n = 227)(n = 227)(n = 214)局部感染(%)21 (9.3)11 (7.4)5 (2.3)菌血症(%)6 (2.6)3
10、(2.3)1 (0.5)Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidone-iodine, alcohol, and chlorexidine for prevention of infection associated with central venous and arterial catheters. Lancet 1991; 338: 339-343CRBSI: 敷料选择Safdar N, OHoro JC, Ghufran A, et al. Chlorhexidine-impregnate
11、d dressing for prevention of catheter-related bloodstream infection: a meta-analysis. Crit Care Med 2014含氯己啶敷料可能具有一定优势CRBSI: 腔内感染的临床表现全身表现发热白细胞增多插管局部表现无其他表现血培养革兰阴性杆菌?CRBSI: 微生物学诊断方法诊断标准诊断标准敏感性敏感性特异性特异性缺点缺点无需拔除CVC的方法同时定量血培养经CVC留取血培养菌落计数相当于外周血培养菌落计数的5倍或更多93%97-100%耗费人力，价格昂贵血培养阳性时间差经CVC留取血培养报警时间较外周血培养报
12、警时间提前 2小时89-90%72-87%若经CVC输注抗生素，结果难以解释经CVC留取定量血培养经CVC留取定量血培养 100 CFU/ml81-86%85-96%无法鉴别CRBSI和菌血症吖啶橙白细胞离心涂片发现任何细菌87%94%未得到广泛应用腔内毛刷定量培养 100 CFU/ml95%84%可能导致菌血症，心律失常或栓塞需要拔除CVC的方法CVC尖端半定量培养，滚动平板导管尖端 15 CFU/ml45-84%85%无法培养腔内细菌CVC定量培养：离心，混旋，超声振荡导管尖端 103 CFU/ml82-83%89-97%临界值尚不明确CVC革兰染色和吖啶橙染色镜检直接看到微生物84-10
13、0%97-100%耗费人力，缺乏实用性Raad I, Hanna H, Maki D. Intravascular catheter-related infections: advances in diagnosis, prevention, and management. Lancet Infect Dis 2007; 7: 645-657CRBSI的DTP: 应当从几个腔留取血标本?对于伴随CRBSI的中心静脉导管，约有40%仅有一个导管腔有细菌显著定植随机选择一个导管腔留取血标本进行培养，得到阴性结果的概率为66%总体上看，随机选择从一个导管腔留取血标本培养60%的概率检测到定植Dobb
14、ins BM, Catton JA, Kite P, et al. Each lumen is a potential source of central venous catheter-related bloodstream infection. Crit Care Med 2003; 31: 1688-1690CRBSI的DTP: 需要留取多少外周血标本?外周血培养数外周血培养数留取两个血培养的留取两个血培养的CRBSI(n = 49)留取三个血培养的留取三个血培养的CRBSI(n = 11)合计合计(n = 60)一个91.9%(83.7 98.0%)90.9%(72.7 100.0%)
15、91.7%两个100%96.9%(81.8 100.0%)99.5%Guembe M, Rodriguez-Creixems M, Sanchez-Carrillo C, et al. Differential time to positivity (DTTP) for the diagnosis of catheter-related bloodstream infection: do we need to obtain one or more peripheral vein blood cultures? Eur J Clin Microbiol Infect Dis 2011 Oct 2
16、1 Epub ahead of print当根据DTP方法确诊CLABSI时，仅留取一个（套）外周血培养并不会明显遗漏CLABSI病例CRBSI的诊断Raad I, Hanna H, Maki D. Intravascular catheter-related infections: advances in diagnosis, prevention, and management. Lancet Infect Dis 2007; 7: 645-657CRBSI初始治疗OGrady NP, Chertow DS. Managing bloodstream infections in patie
17、nts who have short-term central venous catheters. Cleve Clin J Med 2011; 78: 10-17临床怀疑短期留置中心静脉导管相关性血行性感染重症患者轻中症患者（无低血压或器官功能衰竭）拔除导管至少留取2套血培养，其中至少1套来自外周静脉开始经验性抗生素治疗请感染科医生会诊有危险因素*无危险因素拔除导管至少留取2套血培养，其中至少1套来自外周静脉开始经验性抗生素治疗如仍需要导管可保留至少留取2套血培养，其中至少1套来自外周静脉开始经验性抗生素治疗*例如免疫功能抑制，血管内异物，严重全身性感染表现，插管部位感染表现，确诊菌血症或真
18、菌血症CRBSI的治疗: 拔除导管的实际感染率Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001; 286: 700-707. Leon C, Alvarez-Lerma F, Ruiz-Santana S, et al. Antiseptic chamber-containing hub reduces
19、 central venous catheter-related infection: a prospective, randomized study. Crit Care Med 2003; 31: 1318-1324. Ranucci M, Isgro G, Giomarelli PP, et al. Impact of oligon central venous catheters on catheter colonization and catheter-related bloodstream infection. Crit Care Med 2003; 31: 52-59. Dobb
20、ins BM, Catton JA, Kite P, et al. Each lumen is a potential source of central venous catheter-related bloodstream infection. Crit Care Med 2003; 31: 1688-1690. Darouiche RO, Raad II, Heard SO, et al. A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group. N Engl
21、 J Med 1999; 340: 1-8.CRBSI的治疗: 拔管 vs. 不拔管Rijnders BJ, Peetermans WE, Verwaest C, et al. Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized trial. Intensive Care Med 2004; 30: 1073-1080怀疑CRBSI并计划更换中心静脉导管试验组标准治疗组拔除导管留取2套血培养保留导管继续
22、观察5天感染表现缓解不拔除导管感染表现持续拔除导管血培养阳性，或血流动力学不稳定CRBSI的治疗: 拔管 vs. 不拔管标准治疗标准治疗密切观察密切观察p更换中心静脉导管38/3816/42 0.2总住院日4234 0.2ICU病死率10/328/32 0.2Rijnders BJ, Peetermans WE, Verwaest C, et al. Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized
23、trial. Intensive Care Med 2004; 30: 1073-1080CRBSI的治疗: 拔管 vs. 不拔管标准治疗标准治疗(n = 37)保守治疗保守治疗(n = 16)p年龄66.8 20.159.3 16.60.2男性17 (45%)11 (68%)0.127胃肠外营养13 (35%)8 (50%)0.31菌血症时APACHE II15.4 4.615.4 4.40.99菌血症时SOFA7.0 4.47.1 3.40.94颈内静脉33 (89%)16 (100%)双腔导管29 (78%)9 (56%)导管留置天数17.09.214.86.80.35菌血症前住院日25
24、 (3-245)24.5 (9-143)0.69最初24小时充分治疗15 (40%)7 (44%)0.828ICU病死率17 (46%)12 (75%)0.051住院病死率21 (57%)12 (75%)0.208Deliberato RO, Marra AR, Correa TD, et al. Catheter Related Bloodstream Infection (CR-BSI) in ICU Patients: Making the Decision to Remove or Not to Remove the Central Venous Catheter. PLoS ONE
25、2012; 7: e32687CRBSI的初始治疗OGrady NP, Chertow DS. Managing bloodstream infections in patients who have short-term central venous catheters. Cleve Clin J Med 2011; 78: 10-17CRBSI的预防医护协作管理比技术更重要预防CRBSI的质量改进计划质量改进干预措施质量改进干预措施定义与举例定义与举例教育(n = 33)通过讲座传递有关CLABSI的理论知识（针对CLABSI流行病学或预防措施进行每月定期或单次讲座；带有课前与课后考试的教
26、学模块）培训(n = 4)与CVC护理及留置相关的实际技能培训（通过模拟人进行无菌操作留置CVC的个人培训）反馈(n = 20)向ICU医务人员报告CLABSI发生率或感染预防措施依从性（每月在员工会议上报告感染率；改进预防措施依从性或CLABSI发生率的招贴画）临床提醒(n = 15)有关适当临床操作的提醒以改进预防措施的知晓率或实施（有关手卫生或CLABSI发生率的招贴画；每日提醒每位患者的CVC是否可以停用；CVC上贴纸或佩戴徽章提醒正确操作的重要性；信息一览表，流程图或每日目标清单）集束化措施(n = 11)包括至少2项IHI留置或保留CVC期间的预防措施（包括2-5项IHI建议的集束
27、化措施；不包括旨在提高依从性的质量改进措施的集束化措施）清单(n = 18)有关集束化预防措施的清单以提高循证感染预防措施的依从性（CVC置管过程中包括2-5项IHI建议的清单以提高集束化措施的依从性）授权终止操作(n = 10)发现未能正确实施预防措施时，授权护士终止并重新开始CVC置管操作监测依从性(n = 12)护士间断或持续监督CVC置管或留置的预防措施，使用或不使用集束化措施/清单指定负责人(n = 11)指定一名负责人，通过计划各种活动增加知晓程度或介绍技术化措施，以实施质量改进措施事先准备CVC物品(n = 16)使用包括CVC置管或护理各种所需物品的CVC车基础设施改变(n =
28、 2)改变医院基础设施以便提高预防措施的依从性（安装洗手液装置以便医务人员进行手部消毒）组织结构改变(n = 4)有关人员或职责的组织结构改变以提高预防措施的依从性（充足人员以降低患者护士比例；仅有经过培训的人员才能留置CVC；对接受培训人员进行监督）Blot K, Bergs J, Vogelaers D, et al. Prevention of central line-associated bloodstream infections through quality improvement interventions: a systematic review and meta-anal
29、ysis. Clin Infect Dis 2014CRBSI的预防：Central Line Bundle洗手放置导管过程中采用最大限度的隔离措施使用氯己啶消毒皮肤如有可能，避免股静脉置管拔除不必要的导管CRBSI的预防: Central Line BundlePronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006; 355: 2725-2732我们自己的经验CVC护理小组氯己啶敷料弃用正压接头（可来福）抗感染导管vs普通深静脉导管三腔深静脉的应用导管相关性血行性感染CRBSI值得关注腔内感染 vs 腔外感染CRBSI需要早期诊断和治疗集束化管理有助于控制CRBSI多谢聆听
