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气道分泌物培养的临床意义,北京协和医院杜斌,Conflicts of Interest,AstellasAstraZenecaBayerDainippon Sumimoto PharmaEli LillyGlaxoWellcomeMSDPfizer (Wyeth),临床病例,M/75 yoPMHx: 无2010/3/1结肠癌穿孔继发性腹膜炎术后收入ICU感染性休克急性肾功能衰竭DIC住ICU后病情逐渐稳定,临床病例,2010/3/13 ICU Day 12BT 39.8C WCC 16.8 体格检查双肺湿罗音呼吸机条件升高PEEP 8 16FiO2 0.4 0.6PaO2/FiO2 165 80,临床病例,考虑VAP准备应用经验性抗生素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S,VAP发生前的微生物学检查,739名可疑VAP患者入选281名(39%)患者入选前1 3日有培养结果130名(46%)患者培养出致病微生物,Sanders 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: 58-63,VAP发生前的微生物学检查,Sanders 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: 58-63,VAP发生前的微生物学检查,Sanders 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: 58-63,VAP发生前的微生物学检查,经验性抗生素错误率根据革兰染色结果16% (11 33%)根据分离所有微生物37% (29 45%)根据药敏结果39% (31 48%),Sanders 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: 58-63,VAP发生前的微生物学检查,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)的价值患者: 356名心脏手术患者微生物学监测方法: PSB + 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.,VAP发生前的微生物学检查,VAP诊断标准CXR出现新发浸润影或原有浸润影加重下列标准中2条或2条以上:发热( 38.5C)或低体温( 6,TBX诊断标准脓性气管分泌物CXR没有肺炎导致的浸润影下列标准中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.,VAP发生前的微生物学检查,VAP患病率7.87% (28/356)发病率34.5例/1,000机械通气日TBX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.,VAP发生前的微生物学检查,微生物学监测1626个标本平均每名患者4.56 2.8个标本2 30预测准确性VAP1/28TBX1/29,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.,VAP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; 31:1964 1970.,VAP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; 31:1964 1970.,VAP发生前的微生物学检查,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%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; 31:1964 1970.,VAP发生前的微生物学检查,结论VAP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 Culture Results in the Initial Management of Ventilator-associated Pneumonia. Am J Respir Crit Care Med 2002; 165: 41-46,VAP发生前的微生物学检查,结论既往培养结果与怀疑VAP时培养结果一致性很差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 empiric antibiotics in suspected ventilator-associated pneumonia: secondary analysis from a randomized trial. J Crit Care 2008; 23: 58-63,临床病例,决定不考虑既往呼吸道分泌物培养结果经验性抗生素选择?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,VAP治疗 革兰染色结果,Rello J, Paiva JA, Baraibar J, et al. International conference for the development of consensus on the 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 deteriorating,VAP治疗 革兰染色结果,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 1999; 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 injured 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, Adhikari 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: 74-81,VAP治疗 革兰染色结果,Veinstein A, Brun-Buisson C, Derrode N, et al. Validation of an algorithm based on direct examination of specimens in suspected ventilator-associated pneumonia. Intensive Care Med 2006; 32: 676-683,Suspected VAP,PTC Gram stain -veETA Gram stain +ve,ETA & PTC*,ETA Gram stain -ve,PTC Gram stain +ve,Empiric Therapy,Withhold Therapy,Severity Criteria*,Yes,No,*ETA, endotracheal aspirate; PTC, protected telescoping catheter*extensive lung involvement or severe hypoxemia (P/F ratio 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,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 value of surveillance. Crit Care Med 2003; 31:1964 1970.,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,25名非粒细胞缺乏的机械通气患者( 72 h)去世后立即进行尸体解剖, 并采取下呼吸道标本,肺组织病理检查念珠菌病8% (2/25),呼吸道标本培养念珠菌40% (10/25),VS.,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,XIII. What is the significance of 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 candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 503-535,医院获得性肺炎的诊断: 痰培养的准确性,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%,临床病例,如果没有痰培养结果,是否仍然考虑肺炎?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)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,临床病例,如果没有痰培养结果,是否仍然考虑肺炎?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,临床病例,如果没有痰培养结果,是否仍然考虑肺炎?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)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腹部,泌尿系,静脉导管,气管内吸取物常规培养的诊断价值,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,临床病例,考虑肺部化脓性细菌感染气道分泌物培养结果2010/3/12 鲍曼不动杆菌2010/3/13 MRSA2010/3/13 铜绿假单胞菌气道分泌物培养结果不一致致病菌 = ?抗生素选择?,临床病例,考虑肺部化脓性细菌感染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/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I,气管内吸取物常规培养的诊断价值,痰培养阴性致病菌 = 其他菌? (如MRSA)致病菌 = MRSA = 1 - 敏感性= 100% - 82% = 18%连续三次未培养出致病菌的概率= 18% x 18% x 18% = 0.6%,临床病例,2010/3/31临床表现BT 36.8C , WCC 10.8 呼吸机条件降低PEEP 4 , FiO2 0.35 , PaO2/FiO2 248 间断脱机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I,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-A

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