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1、呼吸機(jī)相關(guān)性肺炎呼吸機(jī)相關(guān)性肺炎HAP/VAP: 概要概要 流行病學(xué)流行病學(xué) 診斷策略診斷策略 抗生素治療抗生素治療HAP/VAP: 問(wèn)題問(wèn)題1 呼吸機(jī)相關(guān)性肺炎指應(yīng)用機(jī)械通氣多呼吸機(jī)相關(guān)性肺炎指應(yīng)用機(jī)械通氣多長(zhǎng)時(shí)間以后發(fā)生的肺炎長(zhǎng)時(shí)間以后發(fā)生的肺炎?24小時(shí)小時(shí)48小時(shí)小時(shí)72小時(shí)小時(shí)96小時(shí)小時(shí)1. 48-72小時(shí)小時(shí)HAP/VAP/HCAP: 定義定義 醫(yī)院獲得性肺炎醫(yī)院獲得性肺炎(HAP) 住院住院48小時(shí)后發(fā)生且住院時(shí)不處于潛伏期的肺炎小時(shí)后發(fā)生且住院時(shí)不處于潛伏期的肺炎 呼吸機(jī)相關(guān)性肺炎呼吸機(jī)相關(guān)性肺炎(VAP) 氣管插管氣管插管48小時(shí)以后發(fā)生的肺炎小時(shí)以后發(fā)生的肺炎 因重度因重

2、度HAP需要?dú)夤懿骞苷邞?yīng)按照需要?dú)夤懿骞苷邞?yīng)按照VAP處理處理 醫(yī)療相關(guān)肺炎醫(yī)療相關(guān)肺炎(HCAP) 發(fā)生感染前發(fā)生感染前90天內(nèi)在急性病醫(yī)院住院天內(nèi)在急性病醫(yī)院住院 2天天 在養(yǎng)護(hù)院或長(zhǎng)期醫(yī)療機(jī)構(gòu)住院在養(yǎng)護(hù)院或長(zhǎng)期醫(yī)療機(jī)構(gòu)住院 近期接受靜脈抗生素治療、化療或發(fā)生感染前近期接受靜脈抗生素治療、化療或發(fā)生感染前30天內(nèi)接受傷口治療天內(nèi)接受傷口治療 就診于醫(yī)院門診或透析門診就診于醫(yī)院門診或透析門診ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and h

3、ealthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416 發(fā)病率發(fā)病率 美國(guó)醫(yī)院獲得性感染的第二位美國(guó)醫(yī)院獲得性感染的第二位 5-15例例/1,000住院病例住院病例 罹患率和病死率升高罹患率和病死率升高 預(yù)后預(yù)后 住院日延長(zhǎng)住院日延長(zhǎng)7-9天天 醫(yī)療費(fèi)用增加醫(yī)療費(fèi)用增加$40,000Kumpf G, et al. J Clin Epidemiol 1998; 54: 495-502Lizioli A, et al. J Hosp Infect 2003; 54: 141-148Richards M

4、J, et al. Crit Care Med 1999; 27: 887-8922%/dCook 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 patients. Ann Intern Med 1998;129:440遲發(fā)性遲發(fā)性HAP50%早發(fā)性早發(fā)性HAP50%510d 總病死率總病死率30-70%

5、 : 歸因病死率歸因病死率33-50% H2H2受體拮抗劑進(jìn)行應(yīng)激性潰瘍預(yù)防受體拮抗劑進(jìn)行應(yīng)激性潰瘍預(yù)防 “自由自由”輸血輸血 去白細(xì)胞輸血去白細(xì)胞輸血 血糖控制不佳血糖控制不佳 ARDSARDS 深度鎮(zhèn)靜或肌松深度鎮(zhèn)靜或肌松FagonKollefPapazianRelloTimsitTorres銅綠假單胞菌192927501628不動(dòng)桿菌屬104501224嗜麥芽窄食單胞菌073000腸桿菌屬168004流感嗜血桿菌61810130其他革蘭陰性桿菌24102841032金黃色葡萄球菌20302192620肺炎鏈球菌410744 支氣管遠(yuǎn)端標(biāo)本培養(yǎng)分離出口咽部定植菌(草綠支氣管遠(yuǎn)端標(biāo)本培養(yǎng)分離

6、出口咽部定植菌(草綠色鏈球菌,凝固酶陰性葡萄球菌,奈瑟氏菌屬,色鏈球菌,凝固酶陰性葡萄球菌,奈瑟氏菌屬,棒狀桿菌屬)棒狀桿菌屬) 難以解釋難以解釋 在免疫抑制甚至免疫正?;颊呖赡芤鸶腥驹诿庖咭种粕踔撩庖哒;颊呖赡芤鸶腥綜abello 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 healthy subjects and cronic lung disea

7、ses: a bronchoscopic study. Eur Respir J 1997;10:11371144 金黃色葡萄球菌金黃色葡萄球菌 糖尿病,頭顱創(chuàng)傷,住糖尿病,頭顱創(chuàng)傷,住ICU 厭氧菌:在厭氧菌:在VAP中的重要性尚不明確中的重要性尚不明確 非插管患者誤吸非插管患者誤吸 VAP罕見罕見 肺炎軍團(tuán)菌:發(fā)生率缺乏數(shù)據(jù),但重要性受關(guān)注肺炎軍團(tuán)菌:發(fā)生率缺乏數(shù)據(jù),但重要性受關(guān)注 免疫抑制患者如器官移植,免疫抑制患者如器官移植,HIV,糖尿病,基礎(chǔ)肺病,糖尿病,基礎(chǔ)肺病,終末期腎病終末期腎病012345678Early-onset HAPLate-onset HAPTime from h

8、ospitalization (days)012345678Early-onset VAPLate-onset VAPTime from Intubation (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: 388-416ATS/IDSA. Guidelines for the managem

9、ent of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 問(wèn)題問(wèn)題2 以下哪個(gè)不是呼吸機(jī)相關(guān)性肺炎確切的發(fā)病機(jī)制以下哪個(gè)不是呼吸機(jī)相關(guān)性肺炎確切的發(fā)病機(jī)制 誤吸誤吸 直接吸入直接吸入 血行性播散血行性播散1. 以上答案均不對(duì)以上答案均不對(duì)改變胃排空及胃液pH值的藥物有生物膜的裝置(氣管插管, 鼻胃管)既往應(yīng)用抗生素宿主因素(免疫抑制, 燒傷)消化道細(xì)菌定

10、植細(xì)菌誤吸細(xì)菌吸入醫(yī)院獲得性肺炎水, 藥物溶液及呼吸治療裝置污染感染控制措施不夠(洗手, 隔離衣, 手套)醫(yī)務(wù)人員不足經(jīng)胸種植原發(fā)性菌血癥胃腸道細(xì)菌移位 CXR vs. CT 手術(shù)后肺實(shí)變:敏感性手術(shù)后肺實(shí)變:敏感性0.33 1.00,特異性,特異性 0.79 不同醫(yī)生判讀的一致性不同醫(yī)生判讀的一致性 放射科醫(yī)生:放射科醫(yī)生:kappa 0.27 ICU醫(yī)生:醫(yī)生:12 39%Wunderink RG, Woldenberg LS, Zeiss J, et al. The radiologic diagnosis of autopsy-proven ventilator-associated

11、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 diagnose lung c

12、onsolidation after major abdominal surgery?: a comparison with computed tomography scan. Chest 1992; 102: 1698-703. 胸片新出現(xiàn)浸潤(rùn)影或原有浸潤(rùn)性加重胸片新出現(xiàn)浸潤(rùn)影或原有浸潤(rùn)性加重 以下臨床表現(xiàn)中兩條:以下臨床表現(xiàn)中兩條: T 38C 白細(xì)胞增多或白細(xì)胞缺乏白細(xì)胞增多或白細(xì)胞缺乏 膿性氣道分泌物膿性氣道分泌物敏感性敏感性69%,特異性特異性75%The Canadian Critical Care Trials Group. A randomized trial of diagn

13、ostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630高度可疑VAP = 臨床診斷 + BALF 104 cfu/ml; 可能VAP = 臨床診斷The Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630The Canadian

14、 Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of Ame

15、rica. 2009; 48: 503-535Pugin 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 Pugin J, Auckenthaler R, Mili

16、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 肺不張肺不張 血栓栓塞性疾病血栓栓塞性疾病 胃內(nèi)容物誤吸胃內(nèi)容物誤吸 未治愈社區(qū)獲得性未治愈社區(qū)獲得性肺炎肺炎 充血性心力衰竭充血性心力衰竭HAP/VAP: 治療治療

17、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 2000名連續(xù)收治的名連續(xù)收治的MICU/SICU患者患者 655 (25.8%)罹患感染罹患感染 169 (8.5%)抗生素治療不充分抗生素治療不充分Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of

18、infections. A risk factor for hospital mortality among critically ill patients. Chest 1999; 115: 462-474HAP/VAP: 經(jīng)驗(yàn)性抗生素經(jīng)驗(yàn)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-

19、416ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associa

20、ted pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416ATS/IDSA. Guidelines for the management of adults with hospital

21、-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416培養(yǎng)陰性培養(yǎng)陽(yáng)性培養(yǎng)陰性培養(yǎng)陽(yáng)性培養(yǎng)陰性培養(yǎng)陽(yáng)性培養(yǎng)陰性培養(yǎng)陰性培養(yǎng)陽(yáng)性Hamer DH. Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am

22、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 Agents Chemother 1990;34:269-272Klick JM, du

23、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;55:514-519Heyland D, Dodek P, Muscedere J, et al. Randomized tr

24、ial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 2008; 36(3): 737-744Paul M, Benuri-Silbiger I, Soares-Weiser K, et al. -lactam monotherapy versus -lactam-aminoglycoside combination therapy for sepsis in immunocompetent patie

25、nts: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668Paul 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 randomised trials.

26、BMJ 2004; 328: 668HAP/VAP: 問(wèn)題問(wèn)題3 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-

27、2598 結(jié)果:結(jié)果: 8天與天與15天抗生素療程相比天抗生素療程相比: 病死率、住院日和機(jī)械通氣時(shí)間無(wú)顯著差別病死率、住院日和機(jī)械通氣時(shí)間無(wú)顯著差別 減少了抗生素使用減少了抗生素使用 避免了細(xì)菌耐藥的發(fā)生避免了細(xì)菌耐藥的發(fā)生 PCT指導(dǎo)抗生素治療指導(dǎo)抗生素治療 社區(qū)獲得性下呼吸道感染社區(qū)獲得性下呼吸道感染 不良預(yù)后相似不良預(yù)后相似(15.4% vs. 18,9%),抗生素療程縮短抗生素療程縮短(5.7 d vs. 8.7 d) AECOPD 減少抗生素使用減少抗生素使用(40% vs. 72%), 減少減少6個(gè)月內(nèi)抗生素使用個(gè)月內(nèi)抗生素使用(RR 0.76; 95%CI 0.64 0.92)

28、 社區(qū)獲得性肺炎社區(qū)獲得性肺炎 減少抗生素使用減少抗生素使用(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. JAMA 2009; 302(10): 1059-1066Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerb

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