1、呼吸機相關性肺炎HAP/VAP: 概要流行病學診斷策略抗生素治療預防總結HAP/VAP: 問題1呼吸機相關性肺炎指應用機械通氣多長時間以后發(fā)生的肺炎?A.24小時B.48小時C.72小時D.96小時E.4872小時HAP/VAP/HCAP: 定義醫(yī)院獲得性肺炎（HAP）住院48小時后發(fā)生且住院時不處于潛伏期的肺炎呼吸機相關性肺炎（VAP）氣管插管48小時以后發(fā)生的肺炎因重度HAP需要氣管插管者應按照VAP處理醫(yī)療相關肺炎（HCAP）發(fā)生感染前90天內在急性病醫(yī)院住院 2天在養(yǎng)護院或長期醫(yī)療機構住院近期接受靜脈抗生素治療、化療或發(fā)生感染前30天內接受傷口治療就診于醫(yī)院門診或透析門診ATS/IDS

2、A. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 流行病學發(fā)病率美國醫(yī)院獲得性感染的第二位515例/1000住院病例罹患率和病死率升高預后住院日延長79天醫(yī)療費用增加$40000HAP/VAP: 流行病學Kumpf G, et al. J Clin Epidemiol 1998; 54:

3、495-502Lizioli A, et al. J Hosp Infect 2003; 54: 141-148Richards MJ, et al. Crit Care Med 1999; 27: 887-892HAP/VAP: 流行病學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 patie

4、nts. Ann Intern Med 1998;129:440HAP/VAP: 流行病學HAP/VAP: 病死率總病死率3070%：大多數(shù) HAP患者死于基礎病 歸因病死率3350%VAP的歸因病死率升高與菌血癥、耐藥菌（如銅綠假單胞菌、不動桿菌屬）感染、不恰當?shù)目股刂委煹纫蛩叵嚓P。 HAP/VAP: 危險因素氣管插管和機械通氣平臥位缺乏感染控制措施缺乏ICU感染監(jiān)測經鼻氣管插管緊急插管或再次插管基礎肺病腸道營養(yǎng)氣管插管套囊壓力低HAP/VAP: 危險因素H2受體拮抗劑進行應激性潰瘍預防“自由”輸血去白細胞輸血血糖控制不佳ARDS深度鎮(zhèn)靜或肌松HAP/VAP: 病因學FagonKollef

5、PapazianRelloTimsitTorres革蘭陰性桿菌 55 85%銅綠假單胞菌192927501628不動桿菌屬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革蘭陽性球菌2030%金黃色葡萄球菌20302192620肺炎鏈球菌410744HAP/VAP: 病因學支氣管遠端標本培養(yǎng)分離出口咽部定植菌（草綠色鏈球菌，凝固酶陰性葡萄球菌，奈瑟氏菌屬，棒狀桿菌屬）難以解釋在免疫抑制甚至免疫正?；颊呖赡芤鸶腥綜abello H, Torres A, Celiss R, El-Ebiary M, de la

6、Bellacasa JP, Xaubet A, Gonzalez J, Augusti C, Soler N. Bacterial colonization of distal airways in healthy subjects and cronic lung diseases: a bronchoscopic study. Eur Respir J 1997;10:11371144HAP/VAP: 病因學金黃色葡萄球菌糖尿病，頭顱創(chuàng)傷，住ICU厭氧菌：在VAP中的重要性尚不明確非插管患者誤吸VAP罕見肺炎軍團菌：發(fā)生率缺乏數(shù)據(jù)，但重要性受關注免疫抑制患者如器官移植，HIV，糖尿病，基礎肺

7、病，終末期腎病HAP/VAP: 病因學真菌（包括念珠菌和曲霉菌）器官移植，免疫抑制，中性粒細胞缺乏免疫正?；颊吆币姴《久庖哒Ｕ吆币娏鞲胁《?，副流感病毒，腺病毒，麻疹病毒，呼吸道合胞病毒占病毒的70%HAP/VAP: MDR危險因素既往90天應用抗生素住院5天所在社區(qū)或醫(yī)院病房中抗生素耐藥率高HCAP危險因素發(fā)生感染前90天內在急性病醫(yī)院住院2天在養(yǎng)護院或長期醫(yī)療機構住院家庭輸液治療（包括抗生素）30天內接受慢性透析家庭傷口護理家人有多重耐藥菌感染/定植免疫抑制疾病和（或）治療HAP/VAP: 分類012345678Early-onset HAPLate-onset HAPTime from

8、hospitalization （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: 388-416HAP/VAP: 病因學早發(fā)性HAP/VAP遲發(fā)性HAP/VAP細菌學

9、肺炎鏈球菌銅綠假單胞菌流感嗜血桿菌不動桿菌MSSAMRSA敏感GNB耐藥腸桿菌科大腸桿菌腸桿菌屬肺炎克氏菌ESBL +ve菌變形桿菌屬克雷伯菌屬腸桿菌屬嗜肺軍團菌粘質沙雷氏菌洋蔥伯克霍爾德菌曲霉菌屬預后病情較輕，對預后影響小歸因病死率高病死率低罹患率高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

10、-416HAP/VAP: 概要流行病學診斷策略抗生素治療預防總結HAP/VAP: 問題2以下哪個不是呼吸機相關性肺炎確切的發(fā)病機制A.誤吸B.直接吸入C.血行性播散D.胃腸道細菌移位E.以上答案均不對HAP/VAP: 發(fā)病機制改變胃排空及胃液pH值的藥物有生物膜的裝置（氣管插管，鼻胃管）既往應用抗生素宿主因素（免疫抑制，燒傷）消化道細菌定植細菌誤吸細菌吸入醫(yī)院獲得性肺炎水, 藥物溶液及呼吸治療裝置污染經胸種植原發(fā)性菌血癥胃腸道細菌移位感染控制措施不夠（洗手，隔離衣，手套）醫(yī)務人員不足HAP/VAP: 影像學診斷對于可疑肺炎患者，如果根據(jù)其他臨床表現(xiàn)不能確診，影像學判斷也不能提高診斷的正確性若胸

11、片顯示明顯浸潤影，則鑒別心源性肺水腫、非心源性肺水腫、肺挫傷和肺不張將非常困難各種影像學表現(xiàn)的敏感性和特異性差異很大，診斷準確性均不超過70%支氣管氣像診斷肺炎的準確性最高（64%）HAP/VAP: 影像學診斷CXR vs. CT手術后肺實變：敏感性0.331.00，特異性 0.79不同醫(yī)生判讀的一致性放射科醫(yī)生：kappa 0.27ICU醫(yī)生：1239%Wunderink RG, Woldenberg LS, Zeiss J, et al. The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia.

12、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 consolidatio

13、n after major abdominal surgery?: a comparison with computed tomography scan. Chest 1992; 102: 1698-703.HAP/VAP: 臨床診斷胸片新出現(xiàn)浸潤影或原有浸潤性加重以下臨床表現(xiàn)中兩條：T38白細胞增多或白細胞缺乏膿性氣道分泌物敏感性69%，特異性75%HAP/VAP: 細菌學診斷下呼吸道標本的半定量培養(yǎng)特異性低：培養(yǎng)結果陽性可能僅提示定植敏感性高：培養(yǎng)結果陰性有助于除外感染除非剛剛應用或更換抗生素常導致過度應用抗生素革蘭染色結果結合培養(yǎng)結果有助于指導抗生素治療HAP/VAP: 細菌學診斷PSB

14、ETABAL診斷閾值103 cfu/mL105106 cfu/mL104105 cfu/mL敏感性667673特異性907582特異敏感準確采樣部位越遠，特異性越高，敏感性越低，診斷閾值越低HAP/VAP: 細菌學診斷試驗設計：多中心隨機臨床試驗入選標準：免疫功能正常的成年患者住ICU超過4天后懷疑呼吸機相關性肺炎排除標準：假單胞菌屬或MRSA定植或感染分組：診斷：BALF定量培養(yǎng) vs. ETA的非定量培養(yǎng)治療：美羅培南 + 環(huán)丙沙星 vs. 美羅培南The Canadian Critical Care Trials Group. A randomized trial of diagnost

15、ic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630HAP/VAP: 細菌學診斷ETA（n=374）BAL（n=365）合計（n=739）明確VAP01（0.3）1（0.1）高度可疑VAP0180（49.3）180（24.4）可能VAP310（82.9）134（36.7）444（60.1）無VAP64（17.1）50（13.7）114（15.4）高度可疑VA =臨床診斷+BALF104cfu/ml；可能VAP=臨床診斷The Canadian Critical Care Tria

16、ls Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630HAP/VAP: 細菌學診斷ETABALP值28天病死率18.4%18.9%0.946天時針對性治療74.6%74.2%0.90無抗生素存活天數(shù)10.67.910.47.50.86最高MODS評分8.64.08.33.60.26The Canadian Critical Care Trials Group. A randomized trial of

17、 diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 2006; 355: 2619-2630HAP/VAP: 細菌學診斷呼吸道分泌物分離出念珠菌，很少提示深部念珠菌感染，不應進行抗真菌治療。（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

18、of America. 2009; 48: 503-535HAP/VAP: 綜合診斷CPIS評分012氣管吸取物無無膿性分泌物膿性分泌物CXR浸潤影無浸潤影彌漫性浸潤影局灶性浸潤影肺部浸潤影進展無進展有進展體溫，36.5且38.438.5且38.939或36WCC，109/L4.0且11.011.0 11.0 + 桿狀核0.5PaO2/FiO2，mmHg240或ARDS240且無ARDS的證據(jù)微生物學陰性或少量中等量或大量+革蘭染色發(fā)現(xiàn)同樣微生物Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis o

19、f ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic blind bronchoalveolar lavage fluid. Am Rev Respir Dis 1991;143:1121-1129 肺部感染評分 HAP/VAP: 綜合診斷CPIS評分012氣管吸取物無無膿性分泌物膿性分泌物CXR浸潤影無浸潤影彌漫性浸潤影局灶性浸潤影肺部浸潤影進展無進展有進展體溫，36.5且38.438.5且38.939或36WCC，109/L4.0且11.011.0

20、11.0 + 桿狀核0.5PaO2/FiO2，mmHg240或ARDS240且無ARDS的證據(jù)微生物學陰性或少量中等量或大量+革蘭染色發(fā)現(xiàn)同樣微生物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 Di

21、s 1991;143:1121-1129 CPIS超過6分即診斷HAP HAP/VAP: 鑒別診斷腫瘤結締組織疾病血管炎綜合征肺泡出血藥物誘發(fā)肺泡炎肺不張血栓栓塞性疾病胃內容物誤吸未治愈社區(qū)獲得性肺炎充血性心力衰竭HAP/VAP: 概要流行病學診斷策略抗生素治療預防總結HAP/VAP: 治療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

22、素治療2000名連續(xù)收治的MICU/SICU患者655（25.8%）罹患感染169（8.5%）抗生素治療不充分Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections. A risk factor for hospital mortality among critically ill patients. Chest 1999; 115: 462-474因此，臨床高度懷疑VAP時，立即開始正確的經驗性抗生素治療至關重要HAP/VAP: 經驗性抗生素無MDR致病菌危險因素、任何嚴重程度

23、、早發(fā)性HAP/VAP的初始抗生素可能致病菌推薦抗生素肺炎鏈球菌頭孢曲松流感嗜血桿菌或MSSA左旋氧氟沙星，莫西沙星或環(huán)丙沙星敏感的腸道革蘭陰性桿菌或大腸桿菌氨芐青霉素/舒巴坦肺炎克雷伯菌或腸桿菌屬厄他培南變形桿菌屬粘質沙雷氏菌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: 388-416HAP/VAP:

24、 經驗性抗生素有MDR致病菌危險因素、任何嚴重程度、遲發(fā)性HAP/VAP的初始抗生素可能致病菌推薦抗生素上表中致病菌及抗假單胞菌頭孢菌素（頭孢吡肟，頭孢他啶）MDR致病菌或銅綠假單胞菌抗假單胞菌碳青霉烯（亞胺培南或美羅培南）肺炎克雷伯菌（ESBL+）或不動桿菌屬-內酰胺/-內酰胺酶抑制劑（哌拉西林/他唑巴坦）加抗假單胞菌喹諾酮（環(huán)丙沙星或左旋氧氟沙星）或氨基糖甙（阿米卡星，慶大霉素或妥布霉素）加MRSA利奈唑烷或萬古霉素嗜肺軍團菌ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilato

25、r-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 抗生素劑量抗生素劑量抗假單胞菌頭孢菌素頭孢吡肟12 g，q812 h頭孢他啶2 g q8h抗假單胞菌碳青霉烯亞胺培南500 mg q6h，1 g q8h或美羅培南1 g q8h-內酰胺/-內酰胺酶抑制劑哌拉西林/他唑巴坦4.5 q6h氨基糖甙阿米卡星20 mg/kg/d慶大霉素7 mg/kg/d妥布霉素7 mg/kg/d抗假單胞菌喹諾酮左旋氧氟沙星750 mg qd環(huán)丙沙星400 mg q

26、8h萬古霉素15 mg/kg q12h利奈唑烷600 mg q12hATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416HAP/VAP: 治療ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ven

27、tilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171: 388-416懷疑HAP/VAP遲發(fā)性HAP/VAP或MDR危險因素否是使用窄譜抗生素治療使用廣譜抗生素治療HAP/VAP: 治療ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Re

28、spir Crit Care Med 2005; 171: 388-416第2/3天：培養(yǎng)結果并評價臨床療效（體溫，WCC，CXR，氧合，膿痰，循環(huán)改變及器官功能）除非肺炎的臨床概率低且LRT鏡檢陰性，否則應根據(jù)當?shù)丶毦餍胁≠Y料應用經驗性抗生素采取下呼吸道（LRT）進行培養(yǎng)（定量或半定量）和顯微鏡檢懷疑HAP/VAP/HCAPHAP/VAP: 治療ATS/IDSA. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated p

29、neumonia. Am J Respir Crit Care Med 2005; 171: 388-4164872小時臨床改善尋找其他致病菌，并發(fā)癥，其他診斷或其他感染灶調整抗生素，尋找其他致病菌，并發(fā)癥，其他診斷或其他感染灶考慮停用抗生素如可能抗生素降階梯，治療78天后再次評估否是培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性培養(yǎng)陽性培養(yǎng)陰性HAP/VAP: 局部抗生素局部注射氨基糖甙局部用藥提高細菌學清除率，但不改變臨床預后霧化吸入氨基糖甙或多粘菌素B治療MDR致病菌副作用耐藥率?誘發(fā)支氣管痙攣Hamer DH. Treatment of nos

30、ocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas 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

31、 tobramycin in the treatment of gram-negative bacterial pneumonia. Antimicrob Agents 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

32、 of pneumonia in seriously ill patients. J Clin Invest 1975;55:514-519HAP/VAP: 聯(lián)合用藥抗生素的協(xié)同效應體外試驗證實有效中性粒細胞缺乏或血行性感染患者預防耐藥發(fā)生增加抗菌譜-內酰胺+氨基糖甙-內酰胺+喹諾酮?HAP/VAP: 聯(lián)合用藥美羅培南+環(huán)丙沙星（n=369）vs. 美羅培南（n=371）RR 1.05，95%CI 0.781.42MDR革蘭陰性桿菌感染（n=56）28天細菌學清除：64.1% vs. 29.4%機械通氣時間：10.7（3.3）vs. 15.0（9.3）ICU住院日：14.2（8.1）vs. 2

33、1.2（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. Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 2008; 36(3): 737-744HAP/VAP: 聯(lián)合用藥Paul M, Benuri-Silbiger I, Soares-Weis

34、er K, et al. -lactam monotherapy versus -lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ 2004; 328: 668總病死率RR 0.9095%CI 0.771.06臨床失敗率RR 0.8795%CI 0.780.97細菌學失敗率RR 0.86 95%CI 0.721.02HAP/VAP: 聯(lián)合用藥Paul M, B

35、enuri-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. BMJ 2004; 328: 668針對VAP經驗性治療時，應根據(jù)當?shù)丶毦退幥闆r，選擇適當?shù)目股剡M行單藥治療HAP/VAP: 問題3呼吸機相關性肺炎的抗生素療程應為A.8天B.

36、15天C.肺部感染評分 CPIS評分 6D.血清降鈣素原 PCT 6CPIS6可疑HAP/VAP3天后重新評估CPISCPIS 6：按照肺炎治療CPIS 6：停用環(huán)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): 505-511HAP/VAP: 抗生素療程PCT指導抗生素治

37、療社區(qū)獲得性下呼吸道感染不良預后相似（15.4%vs.18.9%），抗生素療程縮短（5.7 dvs.8.7d）AECOPD減少抗生素使用（40%vs.72%）減少6個月內抗生素使用（RR 0.76，95%CI 0.640.92）社區(qū)獲得性肺炎減少抗生素使用（RR 0.52，95%CI 0.480.58）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 exacerbations of COPD. Chest 2007; 131: 9-19Christ-Crain M, Stolz D, Bingisser R, et