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1、呼吸机相关性肺炎,HAP/VAP:概要,流行病学诊断策略抗生素治疗,HAP/VAP:问题1,呼吸机相关性肺炎指应用机械通气多长时间以后发生的肺炎?24小时48小时72小时96小时48-72小时,HAP/VAP/HCAP:定义,医院获得性肺炎(HAP)住院48小时后发生且住院时不处于潜伏期的肺炎呼吸机相关性肺炎(VAP)气管插管48小时以后发生的肺炎因重度HAP需要气管插管者应按照VAP处理医疗相关肺炎(HCAP)发生感染前90天内在急性病医院住院 2天在养护院或长期医疗机构住院近期接受静脉抗生素治疗、化疗或发生感染前30天内接受伤口治疗就诊于医院门诊或透析门诊,ATS/IDSA.Guideli
2、nes for the management of adults with hospital-acquired,ventilator-associated,and healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:流行病学,发病率美国医院获得性感染的第二位5-15例/1,000住院病例罹患率和病死率升高预后住院日延长7-9天医疗费用增加$40,000,HAP/VAP:流行病学,Kumpf G,et al.J Clin Epidemiol 1998;54:495-502Liziol
3、i A,et al.J Hosp Infect 2003;54:141-148Richards MJ,et al.Crit Care Med 1999;27:887-892,HAP/VAP:流行病学,机械通气,5,10,累积患病率(%),3%/d,1%/d,2%/d,Cook DJ,Walter SD,Cook RJ,Griffith LE,Guyatt GH,Leasa D,Jaeschke RZ,Brun-Buisson C.Incidence of and risk factors for ventilator-associated pneumonia in critically ill
4、 patients.Ann Intern Med 1998;129:440,d,迟发性HAP50%,早发性HAP50%,HAP/VAP:流行病学,机械通气,5,10,累积患病率(%),d,敏感菌引起,预后好,致病菌常是多药耐药菌(MDR),病死率高,HAP/VAP:病死率,总病死率30-70%:大多数 HAP患者死于基础病 归因病死率33-50%VAP的归因病死率升高与菌血症、耐药菌(如铜绿假单胞菌、不动杆菌属)感染、不恰当的抗生素治疗等因素相关。,HAP/VAP:危险因素,气管插管和机械通气平卧位缺乏感染控制措施缺乏ICU感染监测经鼻气管插管,紧急插管或再次插管基础肺病肠道营养气管插管套囊压
5、力低,HAP/VAP:危险因素,H2受体拮抗剂进行应激性溃疡预防“自由”输血去白细胞输血血糖控制不佳ARDS深度镇静或肌松,HAP/VAP:病因学,HAP/VAP:病因学,支气管远端标本培养分离出口咽部定植菌（草绿色链球菌，凝固酶阴性葡萄球菌，奈瑟氏菌属，棒状杆菌属）难以解释在免疫抑制甚至免疫正常患者可能引起感染,Cabello H,Torres A,Celiss R,El-Ebiary M,de la Bellacasa JP,Xaubet A,Gonzalez J,Augusti C,Soler N.Bacterial colonization of distal airways in h
6、ealthy subjects and cronic lung diseases:a bronchoscopic study.Eur Respir J 1997;10:11371144,HAP/VAP:病因学,金黄色葡萄球菌糖尿病，头颅创伤，住ICU厌氧菌：在VAP中的重要性尚不明确非插管患者误吸VAP罕见肺炎军团菌：发生率缺乏数据，但重要性受关注免疫抑制患者如器官移植，HIV，糖尿病，基础肺病，终末期肾病,HAP/VAP:病因学,真菌（包括念珠菌和曲霉菌）器官移植，免疫抑制，中性粒细胞缺乏免疫正常患者罕见病毒免疫正常者罕见流感病毒，副流感病毒，腺病毒，麻疹病毒，呼吸道合胞病毒占病毒的70%,
7、HAP/VAP:MDR危险因素,既往90天应用抗生素住院 5天所在社区或医院病房中抗生素耐药率高HCAP危险因素发生感染前90天内在急性病医院住院 2天在养护院或长期医疗机构住院家庭输液治疗（包括抗生素）30天内接受慢性透析家庭伤口护理家人有多重耐药菌感染/定植免疫抑制疾病和（或）治疗,HAP/VAP:分类,0,1,2,3,4,5,6,7,8,Early-onset HAP,Late-onset HAP,Time from hospitalization(days),0,1,2,3,4,5,6,7,8,Early-onset VAP,Late-onset VAP,Time from Intub
8、ation(days),ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:病因学,ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and healt
9、hcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:问题2,以下哪个不是呼吸机相关性肺炎确切的发病机制误吸直接吸入血行性播散胃肠道细菌移位以上答案均不对,HAP/VAP:发病机制,改变胃排空及胃液pH值的药物,有生物膜的装置(气管插管,鼻胃管),既往应用抗生素,宿主因素(免疫抑制,烧伤),消化道细菌定植,细菌误吸,细菌吸入,医院获得性肺炎,水,药物溶液及呼吸治疗装置污染,感染控制措施不够(洗手,隔离衣,手套),医务人员不足,经胸种植原发性菌血症胃肠道细菌移位,HAP/VAP:影像学诊断,对于
10、可疑肺炎患者，如果根据其他临床表现不能确诊，影像学判断也不能提高诊断的正确性若胸片显示明显浸润影，则鉴别心源性肺水肿、非心源性肺水肿、肺挫伤和肺不张将非常困难各种影像学表现的敏感性和特异性差异很大，诊断准确性均不超过70%支气管气像诊断肺炎的准确性最高(64%),HAP/VAP:影像学诊断,CXR vs.CT手术后肺实变：敏感性0.33 1.00，特异性 0.79不同医生判读的一致性放射科医生：kappa 0.27ICU医生：12 39%,Wunderink RG,Woldenberg LS,Zeiss J,et al.The radiologic diagnosis of autopsy-p
11、roven ventilator-associated pneumonia.Chest 1992;101:458-63.Fagon J,Chastre J,Hance A.Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients.Chest 1993;103:547-53.Beydon L,Saada M,Liu N,et al.Can portable chest x-ray examination accurately
12、diagnose lung consolidation after major abdominal surgery?:a comparison with computed tomography scan.Chest 1992;102:1698-703.,HAP/VAP:临床诊断,胸片新出现浸润影或原有浸润性加重以下临床表现中两条：T 38C白细胞增多或白细胞缺乏脓性气道分泌物,敏感性69%，特异性75%,HAP/VAP:细菌学诊断,下呼吸道标本的半定量培养特异性低：培养结果阳性可能仅提示定植敏感性高：培养结果阴性有助于除外感染除非刚刚应用或更换抗生素常导致过度应用抗生素革兰染色结果结合培养结果
13、有助于指导抗生素治疗,HAP/VAP:细菌学诊断,采样部位越远 特异性越高 敏感性越低 诊断阈值越低,HAP/VAP:细菌学诊断,试验设计:多中心随机临床试验入选标准:免疫功能正常的成年患者住ICU超过4天后怀疑呼吸机相关性肺炎排除标准:假单胞菌属或MRSA定植或感染分组:诊断:BALF定量培养 vs.ETA的非定量培养治疗:美罗培南+环丙沙星 vs.美罗培南,The Canadian Critical Care Trials Group.A randomized trial of diagnostic techniques for ventilator-associated pneumoni
14、a.N Engl J Med 2006;355:2619-2630,HAP/VAP:细菌学诊断,高度可疑VAP=临床诊断+BALF 104 cfu/ml;可能VAP=临床诊断,The Canadian Critical Care Trials Group.A randomized trial of diagnostic techniques for ventilator-associated pneumonia.N Engl J Med 2006;355:2619-2630,HAP/VAP:细菌学诊断,The Canadian Critical Care Trials Group.A rand
15、omized trial of diagnostic techniques for ventilator-associated pneumonia.N Engl J Med 2006;355:2619-2630,HAP/VAP:细菌学诊断,呼吸道分泌物分离出念珠菌，很少提示深部念珠菌感染，不应进行抗真菌治疗(A-III),Pappas PG,Kauffman CA,Andes D,et al.Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases
16、Society of America.2009;48:503-535,HAP/VAP:综合诊断,Pugin J,Auckenthaler R,Mili N,Janssens JP,Lew PD,Suter PM.Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic blind bronchoalveolar lavage fluid.Am Rev Respir Dis 1991;143:1121-1129,肺部感染评分,HAP/V
17、AP:综合诊断,Pugin J,Auckenthaler R,Mili N,Janssens JP,Lew PD,Suter PM.Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic blind bronchoalveolar lavage fluid.Am Rev Respir Dis 1991;143:1121-1129,CPIS超过 6分即诊断 HAP,HAP/VAP:鉴别诊断,肿瘤结缔组织疾病血管炎综合征肺泡出血药物诱发
18、肺泡炎,肺不张血栓栓塞性疾病胃内容物误吸未治愈社区获得性肺炎充血性心力衰竭,HAP/VAP:治疗,Luna CM,Vujacich P,Niederman MS,et al.Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia.Chest 1997;111:676-685,不充分的抗生素治疗,2000名连续收治的MICU/SICU患者655(25.8%)罹患感染169(8.5%)抗生素治疗不充分,Kollef MH,Sherman G,Ward S,et al.Inadequate an
19、timicrobial treatment of infections.A risk factor for hospital mortality among critically ill patients.Chest 1999;115:462-474,因此，临床高度怀疑VAP时，立即开始正确的经验性抗生素治疗至关重要,HAP/VAP:经验性抗生素,ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and healthcare-associated pneum
20、onia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:经验性抗生素,ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:抗生素剂量,ATS/IDSA.Guidelines for the management of adults w
21、ith hospital-acquired,ventilator-associated,and healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:治疗,怀疑HAP/VAP,迟发性HAP/VAP或MDR危险因素,否,是,使用窄谱抗生素治疗,使用广谱抗生素治疗,ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and healthcare-asso
22、ciated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:治疗,怀疑HAP/VAP/HCAP,采取下呼吸道(LRT)进行培养(定量或半定量)和显微镜检,除非肺炎的临床概率低且LRT镜检阴性，否则应根据当地细菌流行病资料应用经验性抗生素,第2/3天：培养结果并评价临床疗效(体温,WCC,CXR,氧合,脓痰,循环改变及器官功能),ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and
23、 healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:治疗,ATS/IDSA.Guidelines for the management of adults with hospital-acquired,ventilator-associated,and healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,48-72小时临床改善,寻找其他致病菌,并发症,其他诊断或其他感染灶,调整抗生素
24、,寻找其他致病菌,并发症,其他诊断或其他感染灶,考虑停用抗生素,如可能抗生素降阶梯,治疗7-8天后再次评估,培养阴性,培养阳性,培养阴性,培养阳性,否,是,培养阴性,培养阳性,培养阴性,培养阴性,培养阳性,培养阳性,培养阴性,培养阴性,培养阳性,HAP/VAP:局部抗生素,局部注射氨基糖甙局部用药提高细菌学清除率，但不改变临床预后雾化吸入氨基糖甙或多粘菌素B治疗MDR致病菌副作用耐药率?诱发支气管痉挛,Hamer DH.Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Ps
25、eudomonas aeruginosa with aerosolized colistin.Am J Respir Crit Care Med 2000;162:328-330.Brown RB,Kruse JA,Counts GW,Russell JA,Christou NV,Sands ML,Endotracheal Tobramycin Study Group.Double-blind study of endotracheal tobramycin in the treatment of gram-negative bacterial pneumonia.Antimicrob Age
26、nts Chemother 1990;34:269-272Klick JM,du Moulin GC,Hedley-Whyte J,Teres D,Bushnell LS,Feingold DS.Prevention of gram-negative bacillary pneumonia using polymyxin aerosol as prophylaxis.II.Effect on the incidence of pneumonia in seriously ill patients.J Clin Invest 1975;55:514-519,HAP/VAP:联合用药,抗生素的协同
27、效应体外试验证实有效中性粒细胞缺乏或血行性感染患者预防耐药发生增加抗菌谱-内酰胺+氨基糖甙-内酰胺+喹诺酮?,HAP/VAP:联合用药,美罗培南+环丙沙星(n=369)vs.美罗培南(n=371)RR 1.05,95%CI 0.78 1.42MDR革兰阴性杆菌感染(n=56)28天细菌学清除：64.1%vs.29.4%机械通气时间：10.7(3.3)vs.15.0(9.3)ICU住院日：14.2(8.1)vs.21.2(14.1)ICU病死率：23.1%vs.29.4%住院病死率：33.3%vs.41.2%,Heyland D,Dodek P,Muscedere J,et al.Randomi
28、zed trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia.Crit Care Med 2008;36(3):737-744,HAP/VAP:联合用药,Paul M,Benuri-Silbiger I,Soares-Weiser K,et al.-lactam monotherapy versus-lactam-aminoglycoside combination therapy for sepsis in immunocom
29、petent patients:systematic review and meta-analysis of randomised trials.BMJ 2004;328:668,HAP/VAP:联合用药,Paul M,Benuri-Silbiger I,Soares-Weiser K,et al.-lactam monotherapy versus-lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients:systematic review and meta-analysis of ran
30、domised trials.BMJ 2004;328:668,针对VAP经验性治疗时，应根据当地细菌耐药情况，选择适当的抗生素进行单药治疗,HAP/VAP:问题3,呼吸机相关性肺炎的抗生素疗程应为8天15天肺部感染评分 CPIS评分 6血清降钙素原 PCT 0.1以上答案都不对,HAP/VAP:抗生素疗程,Chastre J,Wolff M,Fagon JY,et al.Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults:a randomized tria
31、l.JAMA 2003;290(19):2588-2598,结果：8天与15天抗生素疗程相比:病死率、住院日和机械通气时间无显著差别 减少了抗生素使用 避免了细菌耐药的发生 8天：亚组发现非发酵G-杆菌复发（铜绿、不动）,HAP/VAP:抗生素疗程,HAP/VAP:抗生素疗程,对于接受适当的初始经验性治疗的呼吸机相关性肺炎患者，推荐抗生素疗程为8天如果患者初始的经验性抗生素治疗不正确，需要对抗生素进行调整时，没有足够的资料推荐适宜的抗生素疗程。,HAP/VAP:抗生素疗程,环丙沙星 x 3天,抗生素10 21天,抗生素10 21天,CPIS 6,CPIS 6,可疑HAP/VAP,3天后重新评估
32、CPIS,CPIS 6:按照肺炎治疗,CPIS 6:停用环丙沙星,Singh N,Rogers P,Atwood CW,et al.Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit.Am J Respir Crit Care Med 2000;162(2):505-511,HAP/VAP:抗生素疗程,PCT指导抗生素治疗社区获得性下呼吸道感染不良预后相似(15.4%vs.18,9%)，抗生素疗程缩短(5.7 d vs.8.7 d)A
33、ECOPD减少抗生素使用(40%vs.72%)，减少6个月内抗生素使用(RR 0.76;95%CI 0.64 0.92)社区获得性肺炎减少抗生素使用(RR 0.52,95%CI 0.48 0.58),Schuetz P,Christ-Crain M,Thomann R,et al.Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections:The ProHOSP randomized controlled trial
34、.JAMA 2009;302(10):1059-1066Stolz D,Christ-Crain M,Bingisser R,et al.Antibiotic treatment of exacerbations of COPD.Chest 2007;131:9-19Christ-Crain M,Stolz D,Bingisser R,et al.Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia:a randomized trial.Am J Respir Crit Care Med 200
35、6;174:84-93,HAP/VAP:抗生素疗程,PCT 0.25 g/ml推荐应用抗生素PCT 0.5 g/ml强烈推荐应用抗生素,Schuetz P,Christ-Crain M,Thomann R,et al.Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections:The ProHOSP randomized controlled trial.JAMA 2009;302(10):1059-1066,HAP
36、/VAP:疗效评估,应采用临床指标评估初始经验性抗生素疗效(II)。应当联合临床指标和微生物学数据调整经验性抗生素治疗(III)病情改善通常需要48 72小时，此前不应改变治疗，除非病情迅速恶化(III)。疗程第3天常可根据临床指标评估治疗有无反应(II)对于治疗有反应的患者，可以根据培养结果进行抗生素的降阶梯，使用窄谱抗生素进行针对性治疗(II)对治疗无反应患者应重新评估，包括类似肺炎的非感染因素，其他或MDR致病菌，肺外感染灶，以及肺炎并发症。应针对上述原因进行诊断检查(III),ATS/IDSA.Guidelines for the management of adults with h
37、ospital-acquired,ventilator-associated,and healthcare-associated pneumonia.Am J Respir Crit Care Med 2005;171:388-416,HAP/VAP:问题4,呼吸机相关性肺炎最有效的预防措施为床头抬高30应用无创通气持续或间断声门下吸引预防性抗生素胸部物理治疗,HAP/VAP:预防,床头抬高至少30经口气管插管经口留置胃管监测胃残余量并防止腹胀减少抗生素的使用尽早开始适当的营养支持严格控制血糖,使用无创通气避免插管缩短插管时间保持套囊压力20 mmHg间断吸引声门下分泌物口腔护理减少耐药菌定植避免深度镇静或肌松每日唤醒减少镇静药剂量,HAP/VAP:总结,危重病患者HAP/VAP罹患率和病死率较高HAP/VAP的诊断需要综合考虑临床表现、影像学特点及微生物学检查结果HAP/VAP的经验性抗生素治疗至关重要及时根据临床疗效和培养结果进行降阶梯治疗缩短抗生素疗程有助于减少细菌耐药,THE END,
