Chairman, Infectious Diseases, Cleveland Clinic Preventing Central Line-Associated Bloodstream Infections (CLABSIs) 预防中心静脉导管相关的血流感染 Steven M. Gordon, M.D. Chairman, Infectious Diseases, Cleveland Clinic Cleveland医院感染科主任 5/6/12

Financial Disclosures/相关数据披露方: 3M: Infection Prevention Advisory panel /3M感染预防组顾问 Thoratec, Corp: Clinical Events Panel for HeartMate II / Thoratec公司临床事故处理组 ASP/Johnson and Johnson: Advisory Panel: 强生消毒灭菌产品组顾问 以设备为基础通过机械辅助循环疗法来拯救、治疗心力衰竭患者，帮助患者康复的全球领先企业 Thoratec Corporation (Nasdaq: THOR) 宣布，今天来自针对 HeartMate II 左心室辅助系统 (LVAS) 进行的目的疗法 (DT) 决定性试验的数据表明，该设备在统计学上的结果(包括在不会出现致残性中风或无需重新手术来更换或修复血泵的情况下的两年存活率)优于 HeartMate XVE。经 HeartMate II 治疗后患者的存活率为58%，而经 HeartMate XVE 治疗后患者的存活率为24%。 2

Objectives/目标 Definitions and Epidemiology of Catheter Associated Infections 导管相关感染的流行病学及定义 Diagnosis 诊断 Examine strategies aimed at prevention 以预防为目的检查策略 Review treatment and management of intravascular catheter infections 回顾静疗管路感染的治疗及管理

Published Guidelines/发布的指南 Strategies to Prevent Central Line-Associated Bloodstream Infections in Acute Care Hospitals/ 急症护理医院预防CLABSI 的策略指南 Prevention of Intravascular Catheter Related Infections /预防血管内导管的相关感染指南 Mermel LA. Ann Intern Med 2000;132:391 CDC MMWR Rep 51 (RR-10):1-26 (9 August 2000) Management of intravascular catheter-related infections /血管内导管的相关感染的处理指南 IDSA guidelines Clin Inf Dis 2001;32:1249 《美国传染病学会指南》

Resources 资源 SHEA vascular access guidelines / 《美国流行病学会—静脉管路指南》 http://www.shea-online.org/about/compendium.cfm AHRQ Healthcare-Associated Infections / 《卫生保健研究和质量机构—医院感染》 http://www.ahrq.gov/qual/hais.htm On the CUSP: Stop BSI /热门话题：遏制血流感染 http://www.hret.org/quality/projects/stop-bsi.shtml Health Research & Educational Trust (HRET): National Implementation of the Comprehensive Unit-Based Safety Program (CUSP) to Reduce Central Line Associated Blood Stream Infections (CLABSI) in the Intensive Care Unit

Vascular Access: Framing Opportunity and Challenges /脉管通路：机遇与挑战并存 Without venous access few current treatment plans could be administered in hospital /在医院，没有什么治疗能离得开静脉通路 Venous access is most common invasive experience for patients (with phlebotomy) / 对病人来说静脉用药或取血是最平常的手段 Patient satisfaction tied to vascular access / 患者的满意度与静疗效果密切相关 Implementation of vascular access clinical pathway is right thing to do! / 因此，我们应该执行正确的静脉通路临床操作方法 出处: Moureau N et al A new evidence baed approach to vascular access selection And management (submitted)

Classification of Intravascular Catheters /血管内导管的分类 By type of vessel occupied /按置入血管的类型分类 peripheral venous, arterial, central venous / 外周静脉，动脉，中心静脉 Intended life-span /按留置时间分类 temporary, short-term Vs long-term /临时的，短期的 和长期的 Pathway from skin to vessel/按穿刺点与皮肤血管关系分类 tunneled Vs non-tunneled /隧道式、非隧道式 Physical length and number of lumens /按导管 长度和管腔数 long Vs short 长导管、短导管 Special attributes /按导管材质分类 antibiotic or antiseptic impregnated /抗菌导管、抗生素涂层导管

Catheters Used for Venous and Arterial Access /用于动/静脉的导管 Peripheral venous and arterial catheters /外周动、静脉导管 Midline catheters /中等长度导管 Peripherally inserted central venous catheters /PICC Umbilical catheters / 脐导管 Non-tunneled central venous catheters (CVC)/非隧道中心静脉导管 Pulmonary artery catheters /肺动脉导管 Tunneled central venous catheters /隧道式中心静脉导管 Totally implantable (port accessed) /完全置入式（输液港）

CDC Definition for Surveillance Purposes /CDC监测定义 An intravascular catheter that terminates at or close to the heart or in one of the great vessels which is used for infusion, withdrawal of blood, or hemodynamic monitoring. /导管末端位置靠近心脏或大血管，用于输液，抽血，或血流动力学监测。 The following are considered great vessels for the purpose of reporting central-line BSI and counting central-line days in the NHSN system: /下列血管被认为是大血管，需将其置管日上报NHSN(美国医疗安全网)用于统计并报告CVC感染率 Aorta, pulmonary artery, superior vena cava, inferior vena cava, brachiocephalic veins, internal jugular veins, subclavian veins, external iliac veins, common iliac veins, common femoral veins, and in neonates, the umbilical artery/vein. / 主动脉,肺动脉,上腔大静脉,下腔大静脉,头臂静脉,颈静脉,锁骨下静脉,髂外静脉,髂总静脉,股静脉和新生儿,脐静脉 National Healthcare Safety Network (NHSN)

Epidemiology of Central Venous Catheters (CVC) / CVC的流行病学 >1 billion intravascular devices used annually in US /在美国，每年血管装置的使用量>10亿 5 million CVCs inserted in patients in US annually 每年为患者置入500万条CVC 15 million CVC days 1500万的导管日 > 15% complications />15%并发症 mechanical 5-19% /机械性5-19% thrombotic 2-26% /血栓 2-26% infectious 5-26% /感染 5-26%

Peripherally Inserted Central Catheter (PICC) venous thrombosis /PICC静脉 血栓 Non-tunneled central venous catheters /非隧道式中心静脉导管 Workhorse for outpatient IV antibiotics at CCF /我院(Cleveland医院)大量患者在门诊输注抗菌素 Recent introduction of adapter with saline flush (Vs heparin) / 先进的生理盐水（相对于肝素）冲管器 Also, allows blood draws via PICC /允许从PICC导管抽血

Types of Catheter-Associated Infections 导管相关性感染的类型 Catheter colonization /导管细菌定植 growth of organisms from a catheter-segment by either seimquantitative (roll plate) or quantitative (vortex) methods / 半定量或定量培养，导管尖端有微生物生长 Catheter-related bloodstream infection /导管相关血流感染 isolation of the same organism from a blood culture and culture of catheter segment accompanied by clinical signs of bloodstream infection without any other apparent source of infection /从血和导管培养中，找出相同的微生物, 结合血液感染的临床表现，排除其他任何感源 Exit-site infection /出口部感染 Erythema, tenderness, induration or purulence within 2 cm of the exit site of the catheter /发红，疼痛，发硬或化脓至少在穿刺口周围2cm

Periperhal venous catheter (short) infections /外周短导管感染 In adults, replace site no more frequently than 72-96 hours /成人，不要在72-96小时内更换穿刺部位

“Tunnel” Infection or Clinical Exit Infection/隧道式感染或出口部感染 Tenderness, erythema, or site induration >2 cm from the catheter site along the subcutaneous tract of a tunneled (e.g. Hickman) catheter in absence of a bloodstream infection / 隧道式导管(例如Hickman导管)引起的敏感，红肿，或沿着导管穿刺部位皮下有超过2cm的肿块，尚无血流感染 A Hickman line is an intravenous catheter most often used for the administration of chemotherapy or other medications, as well as for the withdrawal of blood for analysis. Some types of Hickman lines are used mainly for the purpose of apheresis or dialysis. Hickman lines may remain in place for extended periods and are used when long-term intravenous access is needed.

CLABSI发病机理 Focus of prevention strategies预防策略 Templte 01 9/9/2017 2:56 PM CLABSI发病机理 Focus of prevention strategies预防策略 15

Biofilm on Intravenous Catheter Connecter 24 hours after Insertion /置入静脉导管24小时后，在连接处出现的生物膜 All invasive medical devices support the development of biofilms. Biofilm is a complex three-dimensional structure that consists of cells, bacteria, and extracellular matrix materials. In this scanning electron micrograph, many bacteria are seen in a matrix of material that also contains a red blood cell. This biofilm developed within 24 hours of catheter insertion. Biofilms may promote development of antimicrobial-resistant infections in several ways: Serving as a nidus for deposition and growth of resistant strains that then are released to cause infection; Creating a permeability barrier to antimicrobial diffusion, so that bacteria imbedded in the biofilm may be exposed to sub-inhibitory concentrations of drug that promotes emergence of resistance; Providing a matrix in which bacteria can exchange resistance factors. Biofilms cannot be prevented but some strategies may decrease the rate at which biofilms are formed and decrease bacterial colonization of biofilms. Scanning Electron Micrograph

CLABSI Pathogens /引起CRBSI的病原体 Templte 01 9/9/2017 2:56 PM CLABSI Pathogens /引起CRBSI的病原体 Coagulase-negative 37% staphylococci /凝固酶阴性金黄色葡萄球菌 S. aureus 金黄色葡萄球菌 13% Enterococcus 肠球菌 13% Gram-negative rods G- 14% Candida spp. 念珠菌 8% CDC National Nosocomial Infections Surveillance Am J Infect Control 1999;27:520 17

Impact of CLABSI/ CLABSI的影响 250,000 cases of CVC-associated bloodstream infections / 25万例CLABSI Increases hospital length of stay 11-23 days /增加住院11-23天 Increases costs /增加花费 $7,288 - $29,156 per CLABSI episode /例CLABSI $670 million - $2.7 billion aggregate U.S. costs annually (adjusted by 2007 CPI) / $ 6.7亿-27亿/年 Smith RL, et al. Chest 1991;100:164-167 Amow PM, et al. Clin Infect Dis 1993:16:778-784 Collignon Pl., Med J Aust 1994; 161:374-378

Complication of S. aureus catheter-related bloodstream infection /金葡菌引起的导管相关性血流感染并发症 Abscess on left ventricular wall 左心室壁脓肿

Nosocomial/healthcare associated bloodstream infection/；医源性血流感染 Templte 01 9/9/2017 2:56 PM Nosocomial/healthcare associated bloodstream infection/；医源性血流感染 Must meet 1 of the following criteria:必须符合下列症状之一 Recognized pathogen in > 1cultures with an organism not identified /至少一套上血培养，确认出相同的病原菌 Fever > 38oC, chills, hypotension and signs and symptoms and positive laboratory findings not related to an infection at another site and common skin contaminant is cultured from > 2 cultures on separate occasions / 发烧>38oC,寒颤,低血压症状和体征,不与其他部位感染相关,在2个以上不同时段培养出皮肤常见微生物 Pt < 1 year has fever > 38oC rectal, hypothermia < 37oC rectal, apnea, or bradycardia AND signs and symptoms and positive laboratory results not related to an infection at another site and common skin contaminant is cultured from > 2 cultures on separate occasions / 患儿<1岁，肛温-->38oC, < 37oC ,无呼吸，心动过缓症状和体征,实验室结果显示不与其他部位感染及皮肤常见污染物培养相关 Horan et al. AJIC 2008:36:309-32, (www.cdc.gov/ncidod/dhqp/nhsn.html 20

NHSN CLABSI Event June 2011 美国医疗安全网CLABSI事件 2011.6 Treatment (pharmacology) no longer plays in to Infection domain / 不再仅仅关注药物治疗 No requirement for how long central venous catheter in place to be considered hospital acquired 判断是否属于院内感染，不再依据CVC在体内留置时间 The National Healthcare Safety Network (NHSN)

检测机构公布的院内血流感染率的可信度调查 JAMA 2010;304:2035-41 检测机构公布的院内血流感染率的可信度调查 The journal of the American medical association

Infection Preventionist Rates Relative to Computer Algorithm: Institutional Variability /感染预防专家对CRBSI的估计值与实际统计值的差距：具有统计学差异 Mean: 3.3/1K Mean 9/ 1K

These CLABSIs are “not preventable /这些CLABSI 是“不可预防的” NHSN HAI definitions do not allow for BSI in patients with mucositis, GVHD, or neutropenia to be classified as secondary – by default counted as CLABSI if central line is present /美国医疗安全网 医院感染的定义不将患者有粘膜炎，移植物抗宿主病，白细胞减少症的继 发血流感染患者归类为医院感染，即使该患者带有导管，继发CLABSI， 也不计算在CLABSI里。 These CLABSIs are “not preventable /这些CLABSI 是“不可预防的” Could harm morale of team and adverse effects in era of public reporting /公布结果可能会打击团队的士气和起反作用 Healthcare-associated infections (HAI) GVHD（graft-versus-host disease)移植物抗宿主病 移植物抗宿主反应是一种特异的免疫现象，是由于移植物组织中的免疫活性细胞与免疫受抑制的、组织不相融性抗原受者的组织之间的反应 1Balzan et al. J Gastroenterology & Hepatology 2007;22:464-71 2Pehar et al. SHEA/Decennial 2010 Abstract #660 3DiGiorgio et al, SHEA 2011 Abstract #220

Modified CLABSI Definition – Eligible Patient Populations /CLABSI定义修正—合理选定人群 BMT recipients with graft versus host disease (GVHD) Patients with hematologic malignancy AND netropenia /骨髓移植患者的排异反应，恶性血液病，白细胞减少症 Considerations/相关 Use of objective criteria to identify eligible patients /合理选定人群 Mucositis excluded – many grading scales, no consensus /排除粘膜炎—许多分级尺度，没有达成共识 Inclusion of patients without hematologic malignancy /不包括恶性血液病患者 Solid organ transplant patients, just liver transplant patients, pediatric patients with short gut syndrome /器官移植患者，肝移植，短肠综合症的小儿 Patients with neutropenia regardless of underlying illness /只要是白细胞减少症患者而不论其原发疾病

The Impact of Central Line Insertion Bundles /采用中心静脉导管置管集束的影响 103 ICUs in Michigan (Keystone Project) /密歇 根州的103个 ICU 试点项目 Use of a checklist / 使用核查清单 Emphasis on teamwork /强调团队合作 Mean CLABSI rate decreased from 7.7/1000 CVC days to 1.4/1000 CVC days /CLABSI 率从 7.7降至1.4每千导管日 Pronvost PJ et al New Engl J Med 2006;35-2725+

The Good/可喜的是: 58% decrease in CLABSIs in ICUs /ICU CLABSI减少58%

The Challenge /挑战 37,000 CLABSIs in Dialysis Patients /有37000例导管相关性血流感染发生于透析管着

Interventions To Prevent Infectious Complications / 防止感染并发症的干预措施 Category IA: Supported by evidence from one properly randomized controlled trial and good evidence to support a recommendation for use

Before Insertion 穿刺前 Engage hospital administration and staff about the culture of safety, including risk of healthcare- associated infections and their prevention. /动员医 院管理者和所有员工一起投身于以安全为文化氛围， 认识到包括医护人员相关感染的风险及其预防。 Educate healthcare personnel involved in central line insertion, care, and maintenance about CLABSI prevention. /培训负责CVC穿刺、维护的医 护人员的CLABSI预防知识

Education and Engagement /教育和参与 Education provided to HCWs on hire and annually /不仅给予新员工入职培训，还要每 年给予培训 Joint Commission also requires we educate the patient/families about CLABSI prevention before insertion /JCI组织认为我们应该在穿刺前，教育患者家 属关于CLABSI的预防 Simulation training /模拟训练

Category IA “DO NOT” Recommendations /IA –不推荐 Do Not Routinely culture catheter tips! /不推荐常规培养导管尖端 Do Not use topical antibiotic ointments or creams on insertion sites/不推荐在穿刺部位使用抗菌素药膏 Do Not use in-line filters routinely /不推荐常规使用血管内过滤网装置 Do Not routinely replace central venous or arterial catheters solely for the purposes of reducing infection /不推荐为预防感染常规更换CVC或动脉导管 In-line Filters The in-line filter screen (IFS) is an in-channel screening solution for medium- to-low flow rate and solid loading applications.

At Insertion/穿刺中 Use an all-inclusive catheter cart or kit that contains everything needed for safe, aseptic catheter insertion / 将所有做无菌穿刺所需要用到的物品放在一 个穿刺车或包中 Use a checklist that has all catheter infection prevention bundle components listed and a healthcare worker using the checklist who is empowered to stop the procedure if a breach in aseptic technique is observed. /使用核查清单将所有 导管穿刺套件按步骤列出以感染。负责核对的医护人员 若发现有违反无菌操作原则的操作时，可终止继续操作

Basic Steps: The CLABSI Prevention Bundle /基本步骤：CLABSI预防集束 Hand hygiene /手卫生 Maximal barrier precautions /最大无菌屏障 Chlorhexidine skin antisepsis of catheter insertion site except very LBW infants /用葡萄糖酸盐氯己定(CHG)作穿刺部位皮肤消毒，及低体重儿除外 Non-femoral vein catheter insertion in adults /成人避免股静脉穿刺 Daily review of line necessity; prompt removal of unnecessary lines /每日检查导管保留的必要性，尽早拔除不再需要的导管

Infection rates with improved hand hygiene 改进手卫生后的感染率 Templte 01 Infection rates with improved hand hygiene 改进手卫生后的感染率 9/9/2017 2:56 PM BACKGROUND: Hand hygiene prevents cross infection in hospitals, but compliance with recommended instructions is commonly poor. We attempted to promote hand hygiene by implementing a hospital-wide programme, with special emphasis on bedside, alcohol-based hand disinfection. We measured nosocomial infections in parallel. METHODS: We monitored the overall compliance with hand hygiene during routine patient care in a teaching hospital in Geneva, Switzerland, before and during implementation of a hand-hygiene campaign. Seven hospital-wide observational surveys were done twice yearly from December, 1994, to December, 1997. Secondary outcome measures were nosocomial infection rates, attack rates of methicillin-resistant Staphylococcus aureus (MRSA), and consumption of handrub disinfectant. FINDINGS: We observed more than 20,000 opportunities for hand hygiene. Compliance improved progressively from 48% in 1994, to 66% in 1997 (p<0.001). Although recourse to handwashing with soap and water remained stable, frequency of hand disinfection substantially increased during the study period (p<0.001). This result was unchanged after adjustment for known risk factors of poor adherence. Hand hygiene improved significantly among nurses and nursing assistants, but remained poor among doctors. During the same period, overall nosocomial infection decreased (prevalence of 16.9% in 1994 to 9.9% in 1998; p=0.04), MRSA transmission rates decreased (2.16 to 0.93 episodes per 10,000 patient-days; p<0.001), and the consumption of alcohol-based handrub solution increased from 3.5 to 15.4 L per 1000 patient-days between 1993 and 1998 (p<0.001). INTERPRETATION: The campaign produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction of nosocomial infections and MRSA transmission. The promotion of bedside, antiseptic handrubs largely contributed to the increase in compliance. 16.9%  9.9% (p=0.04) Pittet D, et al. Lancet 2000;356:1307-1312 36

Improving compliance with hand hygiene: The role model /提高洗手的依从性：示范效应 Templte 01 Improving compliance with hand hygiene: The role model /提高洗手的依从性：示范效应 9/9/2017 2:56 PM HCWs in a room with a senior medical staff person or peer who did not wash their hands were significantly less likely to wash their own hands (OR = 0.2, p < .001) /如果资深人员或组长若不带头严格手卫生，洗手依从性将会大打折扣 Emerg Infect Dis 2003; 9:217-23 37

Prevention Strategy 2: Maximal Barrier Precautions 预防策略2：最大无菌屏障 Templte 01 9/9/2017 2:56 PM 38

Maximal Barrier Precautions /最大的无菌屏障 For the operator placing the central line and for those assisting in the procedure: /为进行中心静脉导管穿刺操作者及其助手准备的流程 Wear cap, mask, sterile gown, and gloves /戴帽子，口罩，无菌衣及手套 Cap should cover all hair /帽子应覆盖所有头发 Mask should cover the nose and mouth/口罩应罩住口鼻 These precautions are the same as for any other surgical procedure that carries a risk of infection /这些预防措施等同于外科手术准备程序以预防感染风险 For the patient/患者: Cover the patient with a large sterile drape, with a small opening for the site of insertion /用无菌大单覆盖患者，在穿刺部位开一小孔

Do Maximal Barrier Precautions Prevent CA-BSI? 最大无菌屏障能预防CA-BSI吗? Templte 01 9/9/2017 2:56 PM Do Maximal Barrier Precautions Prevent CA-BSI? 最大无菌屏障能预防CA-BSI吗? Author & Year 作者及时间 Study Design 科研设计类型 Type of Line 导管类型 OR for infection without MBP 无最大无菌屏障引起的相对危险度 Mermel 1991 Prospective Cross-sectional 前瞻性对照研究 SG 2.2 (p=0.03) Raad 1994 Randomized 随机性前瞻性研究 Central 3.3 (p=0.03) Am J Med 1991;91(3B):197S-205S; Infect Control Hosp Epidemiol 1994;15:231-8 40

Efficacy of Barrier Precautions During CVC Insertion /预防措施在CVC穿刺时的有效性 屏障预防措施 Minimal/最小 Maximal/最大 Cath. Colonization/ 7.2% 2.3%* /导管定植 Cath Sepsis/脓毒血症 3.6% 0.6%* *p≤0.05 Raad et al, ICHE 1994

Prevention Strategy 3: Choice of skin prep 预防策略3：选择皮肤消毒剂 Templte 01 9/9/2017 2:56 PM 42

Antisepsis HICPAC 1999 消毒 –1999版美国医院感染控制实践顾问委员会

Prevention: CHG Skin Prep 预防策略：使用CHG 皮肤消毒剂 Templte 01 9/9/2017 2:56 PM Prevention: CHG Skin Prep 预防策略：使用CHG 皮肤消毒剂 CHG 2% is more effective than povidone iodine (Betadine) - it dries quickly and has longer residual action / 2%CHG较安尔碘更有效，快干并有较久的残留活性 Pooled RR for BSI Ann Intern Med. 2002;136:792-801 44