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1、气道分泌物培养的临床意义气道分泌物培养的临床意义北京协和医院北京协和医院杜斌杜斌Conflicts of InterestvAstellasvAstraZenecavBayervDainippon Sumimoto PharmavEli LillyvGlaxoWellcomevMSDvPfizer (Wyeth)v2临床病例临床病例vM/75 yovPMHx: 无v2010/3/1 结肠癌穿孔继发性腹膜炎v术后收入ICU感染性休克急性肾功能衰竭DICv住ICU后病情逐渐稳定3临床病例临床病例v2010/3/13 ICU Day 12BT 39.8C WCC 16.8 v体格检查双肺湿罗音呼吸机
2、条件升高PEEP 8 16FiO2 0.4 0.6PaO2/FiO2 165 804临床病例临床病例v考虑VAP准备应用经验性抗生素v住院医师意见一周前曾留取痰培养铜绿假单胞菌有助于确定目前致病菌?北京协和医院检验科细菌室姓名：XXX性别：男性年龄：75病房：MICU标本：痰日期：2010/3/5铜绿假单胞菌(Pseudomonas aeruginosa)头孢他啶R哌拉西林/他唑巴坦R头孢哌酮/舒巴坦R亚胺培南S美罗培南S5VAP发生前的微生物学检查发生前的微生物学检查v739名可疑VAP患者入选v281名(39%)患者入选前1 3日有培养结果v130名(46%)患者培养出致病微生物Sande
3、rs KM, Adhikari NKJ, Friedrich JO, et al. Previous cultures are not clinically useful for guiding empiric antibiotics in suspected ventilator-associated pneumonia: secondary analysis from a randomized trial. J Crit Care 2008; 23: 58-636VAP发生前的微生物学检查发生前的微生物学检查Sanders KM, Adhikari NKJ, Friedrich JO, e
4、t al. Previous cultures are not clinically useful for guiding empiric antibiotics in suspected ventilator-associated pneumonia: secondary analysis from a randomized trial. J Crit Care 2008; 23: 58-637VAP发生前的微生物学检查发生前的微生物学检查Sanders KM, Adhikari NKJ, Friedrich JO, et al. Previous cultures are not clin
5、ically useful for guiding empiric antibiotics in suspected ventilator-associated pneumonia: secondary analysis from a randomized trial. J Crit Care 2008; 23: 58-638VAP发生前的微生物学检查发生前的微生物学检查经验性抗生素错误率v根据革兰染色结果16% (11 33%)v根据分离所有微生物37% (29 45%)v根据药敏结果39% (31 48%)Sanders KM, Adhikari NKJ, Friedrich JO, et
6、 al. Previous cultures are not clinically useful for guiding empiric antibiotics in suspected ventilator-associated pneumonia: secondary analysis from a randomized trial. J Crit Care 2008; 23: 58-639VAP发生前的微生物学检查发生前的微生物学检查v目的: 确定微生物学监测对于诊断呼吸机相关肺炎(VAP)及化脓性气管支气管炎(TBX)的价值v患者: 356名心脏手术患者v微生物学监测方法: PSB +
7、 ETA频率: 心脏手术结束后, 拔除气管插管前, 手术后3天, 以及每周一次终止时间: 拔除气管插管, 发生VAP或TBX, 死亡Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 1970.10VAP发生前的微生物学检查发生前的微生物学检查VAP诊断标准vCXR出现新发浸润影或原有浸润影加重v下列标准中2条或2条
8、以上:发热( 38.5C)或低体温( 6TBX诊断标准v脓性气管分泌物vCXR没有肺炎导致的浸润影v下列标准中2条或2条以上:发热( 38.5C)或低体温( 36C)白细胞升高( 12 x 109/L)呼吸道分泌物细菌计数明显升高Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 1970.11VAP发生前的微生物学
9、检查发生前的微生物学检查vVAP患病率7.87% (28/356)发病率34.5例/1,000机械通气日vTBX患病率8.15% (29/356)发病率31.13例/1,000机械通气日Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 1970.12VAP发生前的微生物学检查发生前的微生物学检查v微生物学监测162
10、6个标本平均每名患者4.56 2.8个标本2 30v预测准确性VAP1/28TBX1/29Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 1970.13VAP发生前微生物培养结果发生前微生物培养结果Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneu
11、monia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 1970.14VAP发生前微生物培养结果发生前微生物培养结果Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31
12、:1964 1970.15VAP发生前的微生物学检查发生前的微生物学检查v致病菌仅能发现33% (73/220)的致病菌呼吸道分离细菌的阳性预期值 72 h: 56% 72 h: 13%v患者对38% (47/125)的病例完全没有帮助仅31% (39/125)的病例致病菌完全吻合Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003;
13、31:1964 1970.16VAP发生前的微生物学检查发生前的微生物学检查结论vVAP发生前常规进行微生物检查仅能发现少量致病菌由于分离的多数细菌并不参与其后的VAP发病, 因此培养结果常常引起误导v耐药细菌在引发感染前能够分离到敏感性 70%不能作为经验性抗生素选择的唯一依据v经验性抗生素治疗应当覆盖VAP发生前72小时内呼吸道分离出的细菌Hayon J, Figliolini C, Combes A, Trouillet JL, Kassis N, Dombret MC, Gibert C, Chastre J. Role of Serial Routine Microbiologic
14、Culture Results in the Initial Management of Ventilator-associated Pneumonia. Am J Respir Crit Care Med 2002; 165: 41-4617VAP发生前的微生物学检查发生前的微生物学检查结论v既往培养结果与怀疑VAP时培养结果一致性很差v不应根据既往培养结果指导经验性抗生素治疗Sanders KM, Adhikari NKJ, Friedrich JO, et al. Previous cultures are not clinically useful for guiding empiri
15、c antibiotics in suspected ventilator-associated pneumonia: secondary analysis from a randomized trial. J Crit Care 2008; 23: 58-6318临床病例临床病例v决定不考虑既往呼吸道分泌物培养结果v经验性抗生素选择?v主治医师问题是否等待痰涂片结果?北京协和医院检验科细菌室姓名：XXX性别：男性年龄：75病房：MICU标本：痰日期：2010/3/12镜检结果上皮细胞 25 /LPF涂片结果革兰阴性杆菌大量革兰阳性球菌可见19VAP治疗治疗 革兰染色结果革兰染色结果Quest
16、ionsAnswersIn the case of a negative Grams stain of a respiratory sample of a patient with a suspicion of VAP, would you wait for cultures to start antibiotics?NoDepending on the patient*(10/12)(2/12)Rello J, Paiva JA, Baraibar J, et al. International conference for the development of consensus on t
17、he diagnosis and treatment of ventilator-associated pneumonia. Chest 2001; 120: 955-970*Yes if the clinical situation clearly suggestive of pneumonia and if patient at high risk or clinically deteriorating20VAP治疗治疗 革兰染色结果革兰染色结果完全符合完全符合部分符合部分符合不符合不符合Allaouchiche (n = 51)26205Duflo (n = 67)261922Davis
18、 (n = 155)715430Raghavendran (n = 186)903750Albert (n = 705)389108208总计(n = 1164)602 (51.7)238 (20.4)324 (27.8)仅有1/2的VAP病例ETA革兰染色结果与培养结果相符Allaouchiche B, Jaumain H, Chassard D, et al. Gram stain of bronchoalveolar lavage fluid in the early diagnosis of ventilator-associated pneumonia. Br J Anaesth 1
19、999; 83: 845-849Duflo F, Allaouchiche B, Debon R, et al. An evaluation of the Gram stain in protected bronchoalveolar lavage fluid for the early diagnosis of ventilator-associated pneumonia. Anesth Analg 2001; 92: 442-447Davis KA, Eckert MJ, Reed RL II, et al. Ventilator-associated pneumonia in inju
20、red patients: do you trust your Gram stain? J Trauma 2005; 58: 462-466Raghavendran K, Wang J, Belber C, et al. Predictive value of sputum Gram stain for the determination of appropriate antibiotic therapy in ventilator-associated pneumonia. J Trauma 2007; 62: 1377-1383Albert M, Friedrich JO, Adhikar
21、i NKJ, et al. Utility of Gram stain in the clinical management of suspected ventilator-associated pneumonia: secondary analysis of a multicenter randomized trial. J Crit Care 2008; 23: 74-8121VAP治疗治疗 革兰染色结果革兰染色结果Veinstein A, Brun-Buisson C, Derrode N, et al. Validation of an algorithm based on direc
22、t examination of specimens in suspected ventilator-associated pneumonia. Intensive Care Med 2006; 32: 676-683Suspected VAPPTC Gram stain -veETA Gram stain +veETA & PTC*ETA Gram stain -vePTC Gram stain +veEmpiric TherapyWithhold TherapySeverity Criteria*YesNo*ETA, endotracheal aspirate; PTC, protecte
23、d telescoping catheter*extensive lung involvement or severe hypoxemia (P/F ratio 632665245CPIS ETA-Gram stain 676406058CPIS PTC-Gram stain 666546358Strategy studies83747979Veinstein A, Brun-Buisson C, Derrode N, et al. Validation of an algorithm based on direct examination of specimens in suspected
24、ventilator-associated pneumonia. Intensive Care Med 2006; 32: 676-683这一治疗策略提示PTC革兰染色敏感性73%，特异性83%，PPV 83%，NPV 73%，可能漏诊VAPETA革兰染色敏感性88%，特异性51%，PPV 68%，NPV 78%，可能误诊VAP24When to start abxv怀疑VAP后尽早开始12 h内?v不应等待痰涂片结果即使痰涂片阴性，也需使用经验性抗生素25临床病例临床病例v经验性抗生素选择亚胺培南米诺环素万古霉素vICU day 15痰培养结果回报v是否根据培养结果更换抗生素?北京协和医院检
25、验科细菌室姓名：XXX性别：男性年龄：75病房：MICU标本：痰日期：2010/3/12鲍曼不动杆菌(Acinetobacter baumannii)头孢他啶R哌拉西林/他唑巴坦R头孢哌酮/舒巴坦S亚胺培南I美罗培南I26长期机械通气患者下呼吸道的细菌定植长期机械通气患者下呼吸道的细菌定植v目的：检查接受长期机械通气患者肺泡内细菌负荷v背景：大学医院及长期护理院的呼吸监护病房v患者：接受长期机械通气且无肺炎临床表现的14名患者v指标：右中叶及舌叶BALF的定量培养v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
26、, Hulse G, Palmer LB. Stable Patients Receiving Prolonged Mechanical Ventilation Have a High Alveolar Burden of Bacteria. Chest 2005; 127: 1353-135727机械通气患者的细菌定植机械通气患者的细菌定植(n = 356)Bouza E, Prez A, Muoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the val
27、ue of surveillance. Crit Care Med 2003; 31:1964 1970.28下呼吸道分离出念珠菌的意义下呼吸道分离出念珠菌的意义v25名非粒细胞缺乏的机械通气( 72 h)患者v去世后立即进行肺活检v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v肺组织标本的组织学检查v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 Ca
28、ndida species from respiratory samples in critically ill, non-neutropenic patients: an immediate postmortem histologic study. Am J Respir Crit Care Med 1997; 156: 583-59029下呼吸道分离出念珠菌的意义下呼吸道分离出念珠菌的意义v25名非粒细胞缺乏的机械通气患者( 72 h)v去世后立即进行尸体解剖, 并采取下呼吸道标本肺组织病理检查l念珠菌病8% (2/25)呼吸道标本培养l念珠菌40% (10/25)VS.el Ebiary
29、 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: 583-59030下呼吸道分离出念珠菌的意义下呼吸道分离出念珠菌的意义XIII. What is the significance of
30、Candida isolated from respiratory secretions?Recommendation59. Growth of Candida from respiratory secretions rarely indicates invasive candidiasis and should not be treated with antifungal therapy (A-III)Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candi
31、diasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 503-53531医院获得性肺炎的诊断医院获得性肺炎的诊断: 痰培养的准确性痰培养的准确性v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%v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%32临床病例临床病例v如果没有痰培养结果，是否仍然考虑肺炎?v临床表现BT 39.8C , WCC 16.8 呼吸机条件升高(PEEP 8 16, FiO2 0
32、.4 0.6, PaO2/FiO2 165 80)v体格检查双肺湿罗音气道分泌物白色，量少腹腔引流转为脓性腹部出现压痛/反跳痛/肌紧张33临床病例临床病例v如果没有痰培养结果，是否仍然考虑肺炎?v临床表现高度提示肺以外部位感染腹腔感染明确尚需除外其他部位感染v肺炎诊断不明确气道分泌物性状CXR对称性改变痰培养 = 定植34临床病例临床病例v如果没有痰培养结果，是否仍然考虑肺炎?v临床表现BT 39.8C , WCC 16.8 呼吸机条件升高(PEEP 8 16, FiO2 0.4 0.6, PaO2/FiO2 165 80)v体格检查双肺大量痰鸣音气道分泌物黄色脓性，大量其他部位无明显感染表现
33、腹部，泌尿系，静脉导管35气管内吸取物常规培养的诊断价值气管内吸取物常规培养的诊断价值v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36临床病例临床病例v考虑肺部化脓性细菌感染v气道分泌物培养结果2010/3/12 鲍曼不动杆菌2010/3/13 MRSA2010/3/13 铜绿假单胞菌v气道分泌物培养结果不一致致病菌 = ?抗生素选择?37临床病例临床病例v考虑肺部化脓性细菌感染v气道分泌物培养结果2010/3/12 鲍曼不动杆菌2010/3/13 鲍曼不动杆菌2010/3/13 鲍曼不动杆菌v气道分泌物培养结果一致提示：不动杆菌 = 致病菌针对性应用抗生素头孢哌酮
34、/舒巴坦米诺环素可以考虑停用万古霉素北京协和医院检验科细菌室姓名：XXX性别：男性年龄：75病房：MICU标本：痰日期：2010/3/12鲍曼不动杆菌(Acinetobacter baumannii)头孢他啶R哌拉西林/他唑巴坦R头孢哌酮/舒巴坦S亚胺培南I美罗培南I38气管内吸取物常规培养的诊断价值气管内吸取物常规培养的诊断价值痰培养阴性v致病菌 = 其他菌? (如MRSA)v致病菌 = MRSA = 1 - 敏感性= 100% - 82% = 18%v连续三次未培养出致病菌的概率= 18% x 18% x 18% = 0.6%39临床病例临床病例v2010/3/31v临床表现BT 36.8
35、C , WCC 10.8 呼吸机条件降低PEEP 4 , FiO2 0.35 , PaO2/FiO2 248 间断脱机v体格检查双肺呼吸音明显改善气道分泌物白色，量少其他部位无明显感染表现v气道分泌物培养结果依然阳性北京协和医院检验科细菌室姓名：XXX性别：男性年龄：75病房：MICU标本：痰日期：2010/3/28鲍曼不动杆菌(Acinetobacter baumannii)头孢他啶R哌拉西林/他唑巴坦R头孢哌酮/舒巴坦S亚胺培南I美罗培南I40VAP停用抗生素的临床指标停用抗生素的临床指标v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v症状及体征提示感染得到控制
36、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; 125:1791179941VAP停用抗生素的策略停用抗生素的策略Micek ST, Ward S, Fraser
37、VJ, Kollef MH. A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associated Pneumonia. Chest 2004; 125:1791179942VAP停用抗生素的策略停用抗生素的策略预后预后停用抗生素组停用抗生素组(n = 150)对照组对照组(n = 140)P值值住院病死率住院病死率48 (32.0)52 (37.1)0.357住院日住院日(天天)15.7 18.215.4 15.90.865ICU
38、住院日住院日(天天)6.8 6.17.0 7.30.798机械通气天数机械通气天数5.4 5.75.7 7.10.649继发感染继发感染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. Chest 2004; 125:1791179943气道分泌物培养的临床意义肺炎患
39、者停用抗生素的考虑肺炎患者停用抗生素的考虑v并非细菌学清除肺炎诊断/抗生素使用并不依靠气道分泌物阳性结果致病菌定植菌v临床治愈肺炎相关临床表现改善体温/WCCCXR气道分泌物性状机械通气条件疗程?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 trial. JAMA 2003; 290(19): 2588-259844HAP/VAP: 抗生素疗程抗生素疗
40、程Probability of Survival0102030405060Days after Bronchoscopy0.00.20.40.60.81.015-day 8-dayChastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290(19): 2588-25988-day regimen15-day regimenNonfermenting GNBPulmonary infection recurrence26/64(40.6)16/63(25.4)45气道分泌物培养的临床意义气道分泌物培养结果的临床意义气道分泌物培养结果的临床意义v肺炎临床表现诊断治疗v气道分泌物培养 = 定植菌 or 致病菌除外致病菌v不适用情况无法培养的致病微生物病毒、PCP、非典型病原体中性粒细胞缺乏没有脓性分泌物46
