氣道分泌物培養(yǎng)的臨床意義

1、氣道分泌物培養(yǎng)的臨床意義,北京協(xié)和醫(yī)院杜斌,Conflicts of Interest,AstellasAstraZenecaBayerDainippon Sumimoto PharmaEli LillyGlaxoWellcomeMSDPfizer (Wyeth)…,臨床病例,M/75 yoPMHx: 無2010/3/1結(jié)腸癌穿孔繼發(fā)性腹膜炎術(shù)后收入ICU感染性休克急性腎功能衰竭DIC住ICU后病情逐

2、漸穩(wěn)定,臨床病例,2010/3/13 ICU Day 12BT 39.8°C ?WCC 16.8 ?體格檢查雙肺濕羅音呼吸機條件升高PEEP 8 ? 16FiO2 0.4 ? 0.6PaO2/FiO2 165 ? 80,臨床病例,考慮VAP準備應用經(jīng)驗性抗生素住院醫(yī)師意見一周前曾留取痰培養(yǎng)銅綠假單胞菌有助于確定目前致病菌?,北京協(xié)和醫(yī)院檢驗科細菌室姓名：XXX性別：男性年齡：75病房：

3、MICU標本：痰日期：2010/3/5銅綠假單胞菌(Pseudomonas aeruginosa)頭孢他啶R哌拉西林/他唑巴坦R頭孢哌酮/舒巴坦R亞胺培南S美羅培南S,VAP發(fā)生前的微生物學檢查,739名可疑VAP患者入選281名(39%)患者入選前1 – 3日有培養(yǎng)結(jié)果130名(46%)患者培養(yǎng)出致病微生物,Sanders KM, Adhikari NKJ, Friedrich JO, et

4、 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發(fā)生前的微生物學檢查,Sanders

5、 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 20

6、08; 23: 58-63,VAP發(fā)生前的微生物學檢查,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

7、 a randomized trial. J Crit Care 2008; 23: 58-63,VAP發(fā)生前的微生物學檢查,經(jīng)驗性抗生素錯誤率根據(jù)革蘭染色結(jié)果16% (11 – 33%)根據(jù)分離所有微生物37% (29 – 45%)根據(jù)藥敏結(jié)果39% (31 – 48%),Sanders KM, Adhikari NKJ, Friedrich JO, et al. Previous cultures are not

8、 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發(fā)生前的微生物學檢查,目的: 確定微生物學監(jiān)測對于診斷呼吸機相關(guān)肺炎(VAP)及化膿性氣管支氣管

9、炎(TBX)的價值患者: 356名心臟手術(shù)患者微生物學監(jiān)測方法: PSB + ETA頻率: 心臟手術(shù)結(jié)束后, 拔除氣管插管前, 手術(shù)后3天, 以及每周一次終止時間: 拔除氣管插管, 發(fā)生VAP或TBX, 死亡,Bouza E, Pérez A, Muñoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective

10、 analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –1970.,VAP發(fā)生前的微生物學檢查,VAP診斷標準CXR出現(xiàn)新發(fā)浸潤影或原有浸潤影加重下列標準中2條或2條以上:發(fā)熱(? 38.5?C)或低體溫( 6,TBX診斷標準膿性氣管分泌物CXR沒有肺炎導致的浸潤影下列標準中2條或2條以上:發(fā)熱(? 38.5?C)或低體溫(< 36?

11、C)白細胞升高(? 12 x 109/L)呼吸道分泌物細菌計數(shù)明顯升高,Bouza E, Pérez A, Muñoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –19

12、70.,VAP發(fā)生前的微生物學檢查,VAP患病率7.87% (28/356)發(fā)病率34.5例/1,000機械通氣日TBX患病率8.15% (29/356)發(fā)病率31.13例/1,000機械通氣日,Bouza E, Pérez A, Muñoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospectiv

13、e analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –1970.,VAP發(fā)生前的微生物學檢查,微生物學監(jiān)測1626個標本平均每名患者4.56 ? 2.8個標本[2 – 30]預測準確性VAP1/28TBX1/29,Bouza E, Pérez A, Muñoz P, et al. Ventilator-assoc

14、iated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –1970.,VAP發(fā)生前微生物培養(yǎng)結(jié)果,Bouza E, Pérez A, Muñoz P, et al. Ventilator-associated pneumonia afte

15、r heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –1970.,VAP發(fā)生前微生物培養(yǎng)結(jié)果,Bouza E, Pérez A, Muñoz P, et al. Ventilator-associated pneumonia after heart surgery: A p

16、rospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –1970.,VAP發(fā)生前的微生物學檢查,致病菌僅能發(fā)現(xiàn)33% (73/220)的致病菌呼吸道分離細菌的陽性預期值< 72 h: 56%? 72 h: 13%患者對38% (47/125)的病例完全沒有幫助僅31% (39/125)的病例致病菌完全吻合,Bouz

17、a E, Pérez A, Muñoz 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發(fā)生前的微生物學檢查,結(jié)論VAP發(fā)生前常規(guī)進行微生物檢查僅能發(fā)現(xiàn)少量

18、致病菌由于分離的多數(shù)細菌并不參與其后的VAP發(fā)病, 因此培養(yǎng)結(jié)果常常引起誤導耐藥細菌在引發(fā)感染前能夠分離到敏感性< 70%不能作為經(jīng)驗性抗生素選擇的唯一依據(jù)經(jīng)驗性抗生素治療應當覆蓋VAP發(fā)生前72小時內(nèi)呼吸道分離出的細菌,Hayon J, Figliolini C, Combes A, Trouillet JL, Kassis N, Dombret MC, Gibert C, Chastre J. Role of Ser

19、ial Routine Microbiologic Culture Results in the Initial Management of Ventilator-associated Pneumonia. Am J Respir Crit Care Med 2002; 165: 41-46,VAP發(fā)生前的微生物學檢查,結(jié)論既往培養(yǎng)結(jié)果與懷疑VAP時培養(yǎng)結(jié)果一致性很差不應根據(jù)既往培養(yǎng)結(jié)果指導經(jīng)驗性抗生素治療,Sanders KM

20、, 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;

21、 23: 58-63,臨床病例,決定不考慮既往呼吸道分泌物培養(yǎng)結(jié)果經(jīng)驗性抗生素選擇?主治醫(yī)師問題是否等待痰涂片結(jié)果?,北京協(xié)和醫(yī)院檢驗科細菌室姓名：XXX性別：男性年齡：75病房：MICU標本：痰日期：2010/3/12鏡檢結(jié)果上皮細胞 25 /LPF涂片結(jié)果革蘭陰性桿菌大量革蘭陽性球菌可見,VAP治療 – 革蘭染色結(jié)果,Rello J, Paiva JA, Baraibar J, et

22、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

23、 if patient at high risk or clinically deteriorating,VAP治療 – 革蘭染色結(jié)果,僅有1/2的VAP病例ETA革蘭染色結(jié)果與培養(yǎng)結(jié)果相符,Allaouchiche B, Jaumain H, Chassard D, et al. Gram stain of bronchoalveolar lavage fluid in the early diagnosis of ventilato

24、r-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 p

25、neumonia. 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, Belbe

26、r 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. Util

27、ity 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治療 – 革蘭染色結(jié)果,Veinstein A, Brun-Buisson C, Der

28、rode 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,ET

29、A & 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 hypox

30、emia (P/F ratio < 200), or occurrence of severe sepsis or septic shock,VAP治療 – 革蘭染色結(jié)果,Veinstein A, Brun-Buisson C, Derrode N, et al. Validation of an algorithm based on direct examination of specimens in suspected ven

31、tilator-associated pneumonia. Intensive Care Med 2006; 32: 676-683,Suspected VAP (n = 76),PTC Gram stain -ve(n = 40),ETA Gram stain –ve(n = 21),PTC Gram stain +ve(n = 36),Empiric Therapy,Therapy WithheldPending Cultu

32、res,Severity Criteria,Yes (n = 7),No (n = 12),ETA Gram stain +ve(n = 19),Confirmed VAP(n = 30),Confirmed VAP(n = 4),Confirmed VAP(n = 4),Confirmed VAP(n = 3),VAP治療 – 革蘭染色結(jié)果,Veinstein A, Brun-Buisson C, Derrode N, et

33、 al. Validation of an algorithm based on direct examination of specimens in suspected ventilator-associated pneumonia. Intensive Care Med 2006; 32: 676-683,這一治療策略提示PTC革蘭染色敏感性73%，特異性83%，PPV 83%，NPV 73%，可能漏診VAPETA革蘭染色敏感性

34、88%，特異性51%，PPV 68%，NPV 78%，可能誤診VAP,When to start abx,懷疑VAP后盡早開始12 h內(nèi)?不應等待痰涂片結(jié)果即使痰涂片陰性，也需使用經(jīng)驗性抗生素,臨床病例,經(jīng)驗性抗生素選擇亞胺培南米諾環(huán)素萬古霉素ICU day 15痰培養(yǎng)結(jié)果回報是否根據(jù)培養(yǎng)結(jié)果更換抗生素?,北京協(xié)和醫(yī)院檢驗科細菌室姓名：XXX性別：男性年齡：75病房：MICU標本：痰日期：2010/

35、3/12鮑曼不動桿菌(Acinetobacter baumannii)頭孢他啶R哌拉西林/他唑巴坦R頭孢哌酮/舒巴坦S亞胺培南I美羅培南I,長期機械通氣患者下呼吸道的細菌定植,目的：檢查接受長期機械通氣患者肺泡內(nèi)細菌負荷背景：大學醫(yī)院及長期護理院的呼吸監(jiān)護病房患者：接受長期機械通氣且無肺炎臨床表現(xiàn)的14名患者指標：右中葉及舌葉BALF的定量培養(yǎng)結(jié)果：在進行檢查的32個肺葉中的29個, 至少有一種

36、微生物定量培養(yǎng)> 104 cfu/mL. 多數(shù)肺葉有多種微生物生長,Baram D, Hulse G, Palmer LB. Stable Patients Receiving Prolonged Mechanical Ventilation Have a High Alveolar Burden of Bacteria. Chest 2005; 127: 1353-1357,機械通氣患者的細菌定植(n = 356),Bouza

37、E, Pérez A, Muñoz P, et al. Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003; 31:1964 –1970.,下呼吸道分離出念珠菌的意義,25名非粒細胞缺乏的機械通氣(> 72 h)患

38、者去世后立即進行肺活檢去世后立即進行下呼吸道采樣氣道內(nèi)吸取物保護性毛刷 [PSB]肺泡支氣管灌洗 [BAL]盲目活檢 [平均每例患者14塊組織]雙側(cè)纖維支氣管鏡指導下活檢 [每例患者2塊組織]肺組織標本的組織學檢查呼吸道標本區(qū)分為念珠菌陽性及其他,el Ebiary M, Torres A, Fabregas N, et al. Significance of the isolation of Candida spec

39、ies from respiratory samples in critically ill, non-neutropenic patients: an immediate postmortem histologic study. Am J Respir Crit Care Med 1997; 156: 583-590,下呼吸道分離出念珠菌的意義,25名非粒細胞缺乏的機械通氣患者(> 72 h)去世后立即進行尸體解剖, 并采取下

40、呼吸道標本,肺組織病理檢查念珠菌病8% (2/25),呼吸道標本培養(yǎng)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

41、 immediate postmortem histologic study. Am J Respir Crit Care Med 1997; 156: 583-590,下呼吸道分離出念珠菌的意義,XIII. What is the significance of Candida isolated from respiratory secretions?Recommendation59. Growth of Candida fro

42、m 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 candidia

43、sis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 503-535,醫(yī)院獲得性肺炎的診斷: 痰培養(yǎng)的準確性,敏感性 = 82%肺炎患者培養(yǎng)陽性比例82%肺炎患者培養(yǎng)陰性比例18%特異性 = 0 – 33%非肺炎患者培養(yǎng)陰性比例0 – 33%非肺炎患者培養(yǎng)陽性比例67 – 100%,臨床病例,如果沒有痰

44、培養(yǎng)結(jié)果，是否仍然考慮肺炎?臨床表現(xiàn)BT 39.8°C ?, WCC 16.8 ?呼吸機條件升高(PEEP 8 ? 16, FiO2 0.4 ? 0.6, PaO2/FiO2 165 ? 80)體格檢查雙肺濕羅音氣道分泌物白色，量少腹腔引流轉(zhuǎn)為膿性腹部出現(xiàn)壓痛/反跳痛/肌緊張,臨床病例,如果沒有痰培養(yǎng)結(jié)果，是否仍然考慮肺炎?臨床表現(xiàn)高度提示肺以外部位感染腹腔感染明確尚需除外其他部位感染肺炎診斷不明確氣

45、道分泌物性狀CXR對稱性改變痰培養(yǎng) = 定植,臨床病例,如果沒有痰培養(yǎng)結(jié)果，是否仍然考慮肺炎?臨床表現(xiàn)BT 39.8°C ?, WCC 16.8 ?呼吸機條件升高(PEEP 8 ? 16, FiO2 0.4 ? 0.6, PaO2/FiO2 165 ? 80)體格檢查雙肺大量痰鳴音氣道分泌物黃色膿性，大量其他部位無明顯感染表現(xiàn)腹部，泌尿系，靜脈導管,氣管內(nèi)吸取物常規(guī)培養(yǎng)的診斷價值,某些致病菌(如銅綠假單胞菌

46、)培養(yǎng)為陰性時, 可以除外其感染,,致病菌定植菌,,臨床病例,考慮肺部化膿性細菌感染氣道分泌物培養(yǎng)結(jié)果2010/3/12 鮑曼不動桿菌2010/3/13 MRSA2010/3/13 銅綠假單胞菌氣道分泌物培養(yǎng)結(jié)果不一致致病菌 = ?抗生素選擇?,臨床病例,考慮肺部化膿性細菌感染氣道分泌物培養(yǎng)結(jié)果2010/3/12 鮑曼不動桿菌2010/3/13 鮑曼不動桿菌2010/3/13 鮑曼不動桿菌氣道分泌物培養(yǎng)結(jié)果一致

47、提示：不動桿菌 = 致病菌針對性應用抗生素頭孢哌酮/舒巴坦米諾環(huán)素可以考慮停用萬古霉素,北京協(xié)和醫(yī)院檢驗科細菌室姓名：XXX性別：男性年齡：75病房：MICU標本：痰日期：2010/3/12鮑曼不動桿菌(Acinetobacter baumannii)頭孢他啶R哌拉西林/他唑巴坦R頭孢哌酮/舒巴坦S亞胺培南I美羅培南I,氣管內(nèi)吸取物常規(guī)培養(yǎng)的診斷價值,痰培養(yǎng)陰性致病菌 =

48、 其他菌? (如MRSA)致病菌 = MRSA = 1 - 敏感性= 100% - 82% = 18%連續(xù)三次未培養(yǎng)出致病菌的概率= 18% x 18% x 18% = 0.6%,臨床病例,2010/3/31臨床表現(xiàn)BT 36.8°C ?, WCC 10.8 ?呼吸機條件降低PEEP 4 ?, FiO2 0.35 ?, PaO2/FiO2 248 ?間斷脫機體格檢查雙肺呼吸音明顯改善氣道分泌物白色，

49、量少其他部位無明顯感染表現(xiàn)氣道分泌物培養(yǎng)結(jié)果依然陽性,北京協(xié)和醫(yī)院檢驗科細菌室姓名：XXX性別：男性年齡：75病房：MICU標本：痰日期：2010/3/28鮑曼不動桿菌(Acinetobacter baumannii)頭孢他啶R哌拉西林/他唑巴坦R頭孢哌酮/舒巴坦S亞胺培南I美羅培南I,VAP停用抗生素的臨床指標,確認引起肺部浸潤影的非感染性因素(如肺不張, 肺水腫)從而無需抗

50、生素治療癥狀及體征提示感染得到控制體溫? 38.3?C白細胞計數(shù) 25%胸片表現(xiàn)改善或無進展膿性痰消失PaO2/FiO2 > 250(停用抗生素時須滿足所有上述標準),Micek ST, Ward S, Fraser VJ, Kollef MH. A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically S

51、uspected Ventilator-Associated Pneumonia. Chest 2004; 125:1791–1799,VAP停用抗生素的策略,Micek ST, Ward S, Fraser VJ, Kollef MH. A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Venti

52、lator-Associated Pneumonia. Chest 2004; 125:1791–1799,VAP停用抗生素的策略,Micek ST, Ward S, Fraser VJ, Kollef MH. A Randomized Controlled Trial of an Antibiotic Discontinuation Policy for Clinically Suspected Ventilator-Associat

53、ed Pneumonia. Chest 2004; 125:1791–1799,肺炎患者停用抗生素的考慮,并非細菌學清除肺炎診斷/抗生素使用并不依靠氣道分泌物陽性結(jié)果致病菌?定植菌臨床治愈肺炎相關(guān)臨床表現(xiàn)改善體溫/WCCCXR氣道分泌物性狀機械通氣條件療程?,Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic the

54、rapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290(19): 2588-2598,HAP/VAP: 抗生素療程,Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-as