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1、Hospital-Acquired Pneumonia (HAP): Definitions,HAP: Arises 48 hours or more after hospital admission Is not incubating at the time of admission Ventilator-associated pneumonia (VAP): Arises 48-72 hours or more after endotracheal intubation Healthcare-associated pneumonia (HCAP): Arises within 90 day
2、s of having been admitted to an acute care facility & pt. has resided in a nursing home or LTCF,(American Thoracic Society/IDSA. Am J Respir Crit Care Med 2005;171:388-416),2008年美国CDC停止使用nosocomical pneumonia这个词,使用“医疗相关感染”（health careassociated infection）或缩写为HAI，不再使用nosocomial（医院内的）一词 医院获得性肺炎也改用医疗相关
3、肺炎（health careassociated pneumonia），英文缩写仍为HAP，停止使用nosocomical pneumonia一词,2019/1/24,Dr.HU Bijie,2,Hospital Location & Relative Frequency of HAP & VAP,HAP 14%,ICU HAP 37.5%,Non-ICU HAP 62.5%,VAP 86%,Non-ICU HAP ICU HAP VAP ICU HAP,HAP,ICU,(Kumpf G et al. J Clin Epidemiol 1998;54:495-502) (Lizioli A e
4、t al. J Hosp Infect 2003;54:141-148) (Richards MJ et al. Crit Care Med 1999;27:887-892),2019/1/24,Dr.HU Bijie,4,Diagnosis 诊断,Non-invasive Strategy for Diagnosing HAP/VAP,Clinical approach New lung infiltrate new onset fever, leukocytosis or purulent sputum non-quantitative bacterial analysis of endo
5、tracheal aspirate Drawback relatively non-specific for HAP Heyland et al. demonstrated adequacy of clinical criteria for VAP diagnosis in RCT (BAL with quantitation vs. non-quantitative endotracheal aspirate): no difference in 28 d mortality or LOS in ICU or hospital,(ATS, Am J Respir Crit Care Med
6、1996;153:1711-1725) (Helling TS, Van Way C, Krantz S, et al. Am J Surg 1996;171:570-575) (Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-1536) (Canadian Critical Care Trials Group. NEJM 2006;355:2619-2630),2019/1/24,Dr.HU Bijie,6,肺部感染临床诊断困难： “类肺炎”,充血性心衰，肺栓塞 急性肺损伤与ARDS 过敏性肺炎
7、，嗜酸细胞浸润性肺炎 放射性肺炎 血管炎，Wegeners肉芽肿 隐源性机化性肺炎 过敏性肺曲霉菌病 肺泡蛋白沉积症 结缔组织病肺累及 肿瘤引起阻塞性肺炎 增生性淋巴性疾病，假性/淋巴瘤 白血病肺内浸润,2019/1/24,Dr.HU Bijie,7,呼吸道分泌物细菌检查 要重视定量或半定量培养,HAP特别是VAP痰标本病原学检查的问题主要是假阳性； 培养结果意义的判断需参考细菌浓度； 要常规作血培养（敏感性25%; 阳性也可能肺外感染) 咳痰标本分离的CoNS、除奴卡菌外的其他GPB、除流感嗜血杆菌外的嗜血杆菌属、微球菌、肠球菌、念珠菌属和厌氧菌临床意义不明确； 部分重症肺炎在经验性治疗失败
8、后，应尽早衡量利弊开展稍带创伤的病原学采样技术如PSB采样和防污染BAL。 ICH应重视特殊病原体（真菌、肺孢子菌、分支杆菌、CMV）的检查，必要时经支气管肺活检甚至开胸活检。,Diagnosis of VAP in the ICU: Quantitative BAL vs. Nonquantitative Endotracheal Aspirate (ETA),Primary Outcome,Secondary Outcomes,Response,18.9%,18.4% *,74.2%,74.6%*,10.4d,10.6d*,12.3d,12.2d*,8.3,8.6*,(Canadian C
9、ritical Care Trials Group. NEJM 2006;355:2619-2630),* = NS,Non-invasive Strategy for Diagnosing HAP/VAP,Clinical approach: CPIS clinical pulmonary infection score Quantitative prediction model using clinical criteria May improve clinical diagnosis of HAP 72%-85% sensitive, 85%-91% specific Only vali
10、dated in several small studies,(Pugin J, Auckenthaler R, Mili N, et al. Am Rev Respir Dis 1991;143:1121-1129) (Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-1536),2019/1/24,Dr.HU Bijie,10,临床肺部感染指数（CPIS）,CPIS 6，则高度怀疑存在HAP,(Pugin J, et al. Am Rev Respir Dis 1991; 143:1121-11
11、29),Short Course Therapy of Suspected VAP Using the CPIS,CPIS on diagnosis with 5 criteria: fever, WBC, trach secretions, oxygen, X-ray CPIS on day 3 with 7 criteria: add x-ray progression, culture data.,(Singh N et al. AJRCCM 2000;162:505-511),Invasive Strategy for Diagnosing HAP/VAP,Quantitative c
12、ulture approach: bronchoscopic protected specimen brush (103 CFU/ml) 67% sensitive, 95% specific bronchoalveolar lavage (104 CFU/ml) 73% sensitive, 82% specific quantitative endotracheal aspirate (105 CFU/ml) 38-100% sensitive, 14-100% specific Antibiotic use more appropriate and accurate Claim of i
13、mproved survival at 28 days,(Fagon JY, Chastre J, Wolff M, et al. Ann Intern Med 2000;132:621-630) (Craven DE, and Steger KA, et al. Infect Cont Hosp Epidemiol 1997;18:783-795) (Grossman RF and Fein A. Chest 2000;117:177S-181S),(Shorr Crit Care Med 2005;33:46-53),Meta-analysis of Bronchoscopy: Morta
14、lity,Figure 1 Diagnostic Algorithm for HAP,Figure 1 (contd) Diagnostic Algorithm for HAP,Figure 2 Diagnostic Algorithm for VAP,Figure 2 (cont) Diagnostic Algorithm for VAP,2019/1/24,Dr.HU Bijie,18,特殊和危重病例的快速结果,当天涂片报告 次日初步培养结果：有无细菌生长，大致细菌种类和浓度 2448h药敏结果（可能尚无细菌鉴定） 缩短时间方法：减少不必要的菌落纯分，快速鉴定和药敏，改进报告形式与发送方式
15、,微生物实验室需要改变流程,2019/1/24,Dr.HU Bijie,19,Severity assessment 严重度评估,2019/1/24,Dr.HU Bijie,20,重症肺炎标准,次要标准：3条 呼吸30次/分 PaO2/FiO2 250 多肺叶浸润 意识障碍 尿毒症UN20mg/dL 血WBC 4000 /mm3 血小板100,000 /mm3 体温（深部）36C 低血容量性休需要大量静脉补液,主要标准：1条 感染性休克需用升压药物 急性呼吸衰竭，需要气管插管/机械通气 肾衰？ 肺炎快速发展？,IDSA/ATS: Consensus Guidelines on the Mana
16、gement of Community-Acquired Pneumonia in Adults (Clinical Infectious Diseases 2007; 44:S2772),2019/1/24,Dr.HU Bijie,21,Antimicrobial therapy 抗感染治疗,2019/1/24,Dr.HU Bijie,22,2019/1/24,Dr.HU Bijie,22,医院内肺炎的病原构成,Pathogens to Consider When Treating HAP/VAP,(American Thoracic Society/IDSA. Am J Respir Cr
17、it Care Med 2005;171:388-416),Frequency of bacterial pathogens in HAP in North America: 2,712 strains (SENTRY, Antimicrobial Surveillance Program, Jan.-June 2000),(Hoban DJ et al. Diag Microbiol Infect Dis 2003;45:279-285),Microbiology of VAP at Three Barnes-Jewish Christian HealthCare Hospitals (Te
18、aching, Community & Pediatric), 1998-2001 (N=753 Episodes),(Babcock HM et al. Infect Control Hosp Epidemiol 2003;24:853-858),2019/1/24,Dr.HU Bijie,26,SICU64例VAP病原谱构成 （20032005年复旦大学附属中山医院）,2019/1/24,Dr.HU Bijie,27,Figure 1. Initial Empiric Antibiotic Therapy of HAP,Diagnosis of HAP,Mild-Moderate Pres
19、entation Group 1,Mild-Moderate Presentation + Risk Factors for Resistance Group 2,Severe Presentation Group 3,Treat on Ward with IV/Oral Monotherapy for Core Pathogens for 7-8 days,Treat on Ward with IV/Oral Monotherapy for Core Pathogens and Possible Resistant Pathogens for 7-8 days,Treat in ICU wi
20、th IV Combination Therapy *IV Initially,Streamline Therapy Based on Culture Results,Modify Treatment if Resistant Pathogens Present,*Resistant Pathogens such as: P. aeruginosa, Acinetobacter spp., S. maltophilia and MRSA may require longer durations of treatment (14 da),Streamline Therapy Based on C
21、ulture Results,Figure 2. Initial Empiric Antibiotic Therapy of VAP,Diagnosis of VAP in ICU,Moderate Presentation Group 4,Severe Presentation and/or Risk Factors for Resistance Group 5,Treat in ICU with IV Monotherapy for 7-8 Days,Treat in ICU with Combination Therapy* IV Initially,Streamline Therapy
22、 Based on Culture Results (Monotherapy IV may be appropriate for 7-8 days),*Resistant Pathogens such as: P. aeruginosa, Acinetobacter spp., S. maltophilia and MRSA may require longer durations of treatment (14 da),Streamline Therapy Based on Culture Results,*mild-moderate presentation: no hypotensio
23、n, intubation, sepsis syndrome, rapid progression of infiltrates or multiple organ dysfunction.,HAP: Group 1 Mild-Moderate Presentation*, Early Onset ( 5 days), and No Risk Factors for Resistance.,Treatment of HAP: Group 1,No risk factors for resistance+ mild-moderate presentation Treatment: 3rd gen
24、eration non-pseudomonal cephalosporin (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV) or 4th generation cephalosporin (cefepime 1-2g q12h IV) OR beta-lactam/beta-lactamase inhibitor (eg. piperacillin-tazobactam 4.5 g q8h IV) OR fluoroquinolone (levofloxacin 750 mg IV qd or moxifloxacin 400 mg I
25、V qd) po,HAP: Group 2- Mild-Moderate Presentation, and Risk Factors for Resistance (Prior Antimicrobial Therapy in Preceding 90 days and/or Hospitalization for 5 days).,Treatment of HAP: Group 2,Risk factors for resistance, and/or late onset + mild-moderate presentation (Contd) Treatment:3rd generat
26、ion non-pseudomonal cephalosporin (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV) or 4th generation cephalosporin (cefepime 1-2 g q12h IV) OR piperacillin-tazobactam 4.5 g q8h IV OR imipenem 500 mg q6h IV OR meropenem 500 mg q6h IV OR levofloxacin 750 mg q24h IV OR moxifloxacin 400 mg q24h IV +
27、/- vancomycin 1 g q12h IV or linezolid 600 mg q12h IV,Treatment of HAP: Group 2 (contd),Risk factors for resistance, and/or late onset ( 5 days)+ mild-moderate presentation (Contd) Treatment (contd): For suspected P. aeruginosa : beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam 4.5 g q6
28、h IV) or antipseudomonal cephalosporin (ceftazidime or cefepime 2 g q8h IV) or carbapenem (imipenem or meropenem 1 g q8h IV) plus fluoroquinolone (ciprofloxacin 400 mg q8h IV or 750 mg BID po or levofloxacin 750 mg q24h IV/po) or aminoglycoside (gentamicin or tobramycin 5-7 mg/kg q24h IV or amikacin
29、 15-20 mg/kg q24h IV),HAP: Group 3- Severe Presentation, &/or Risk Factors for Resistance (Prior Antimicrobial Therapy in Preceding 90 days and/or Hospitalization for 5 days),HAP: Group 3-Severe Presentation (Hypotension, Need for Intubation, Sepsis Syndrome, Rapid Progression of Infiltrates or End
30、Organ Dysfunction) and/or Risk for Resistance,Treatment: Treat with combination therapy: anti-pseudomonal cephalosporin (ceftazidime or cefepime 2 g q8h IV) or beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam 4.5 g q6h IV) or carbapenem (imipenem or meropenem 1g q8h IV or 1 g q8h IV) pl
31、us fluoroquinolone (ciprofloxacin 400 mg q8h IV or levofloxacin 750 mg q24h IV) or aminoglycoside (gentamicin or tobramycin 5-7mg/kg qd IV or amikacin 15-20 mg/kg qd IV) +/- vancomycin 1 g q12 h IV or linezolid 600 mg q12 h IV if MRSA present or suspected,VAP: Group 4-Moderate Presentation, No Risk
32、Factors for Resistance and Early Onset 5 days.,Treatment of VAP: Group 4,No risk factors for resistance, early onset (5 days of hospitalization) & moderate presentation Treatment: 3rd generation non-pseudomonal cephalosporin (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV) or 4th generation ceph
33、alosporin (cefepime 2 g q12h IV) OR beta-lactam/beta-lactamase inhibitor (eg. piperacillin-tazobactam 4.5 g q6h IV) OR fluoroquinolone (levofloxacin 750 mg IV qd, moxifloxacin 400 mg IV qd po,Therapy of VAP: Group 5,Group 5 Risk factors for antimicrobial resistance present, late onset and/or severe
34、presentation,Risk factors for antimicrobial resistance present: - Prolonged hospitalization - Prior hospital antimicrobial therapy within 90 d - ICU stay 5 days - Structural lung disease - P. aeruginosa or Acinetobacter spp. Severe presentation - hypotension, intubation, severe sepsis, rapid progres
35、sion of infiltrates or organ dysfunction,VAP: Group 5-Severe Presentation, Risk Factors for Antimicrobial Resistance, and/or Late Onset 5 Days,Treatment of VAP: Group 5,Risk factors for resistance present +/- severe presentation (Contd) Treatment: ceftazidime 2 g q8h IV or cefepime 2g q8h IV OR imip
36、enem-cilastatin 1 g q8h IV OR meropenem 1 g q8h IV OR piperacillin-tazobactam 4.5 g q6h IV PLUS ciprofloxacin 400 mg q8h IV or levofloxacin 750 mg q24h IV OR gentamicin or tobramycin 5-7 mg/kg q24h IV or amikacin 15-20 mg/kg q24h IV +/- vancomycin 1 g q12h IV or linezolid 600 mg q12h IV,2019/1/24,Dr
37、.HU Bijie,42,HAP或VAP初期经验性抗生素治疗 （早发、无MDR危险因素），ATS2005,2019/1/24,43,MDR引起HAP、HCAP和VAP的危险因素,90天内用过抗生素治疗 本次住院时间5天 所在社区或病区的抗生素耐药率较高 出现HAP的危险因素 90天内住院时间2天 居住在养老院或护理院 家庭输液治疗（包括抗生素治疗） 30天内进行慢性透析 家庭清创 家庭成员中有MDR病原菌感染 免疫抑制疾病和/或治疗,2019/1/24,Dr.HU Bijie,44,HAP、VAP、HCAP初期经验性治疗 （晚发、MDR危险因素）,2019/1/24,Dr.HU Bijie,4
38、5,VAP(呼吸机相关肺炎)的经验治疗,Ref: Sanford Guide 2007-2008; *CCM 34:2069, 2006,2019/1/24,Dr.HU Bijie,46,VAP的治疗原则,VAP经验性治疗不应拖延 经验性抗生素治疗对VAP患者预后至关重要，早期错误抗生素治疗可以导致病死率升高，应根据医院常见致病菌的具体情况选择抗生素。 可以根据机械通气时间和既往抗生素治疗情况确定感染致病菌 对于多数致病菌而言，可以采用广谱抗生素进行单药治疗，而高度耐药致病菌如铜绿假单胞菌(PSA)应联合应用-内酰胺和氨基糖甙/氟喹诺酮。 如金葡菌感染，则必须早期、及时地使用糖肽类抗生素。 根
39、据培养的药敏结果对经验性抗生素进行调整（降阶梯），以防止耐药性发生。 多数专家认为，除 PSA 或 MRSA 外，多数VAP仅需7天的抗生素治疗。,2019/1/24,Dr.HU Bijie,47,合适的抗感染治疗 不仅仅是选择敏感的抗菌药物,新治疗方案 第一时间给予恰当治疗 使用广谱抗生素 优化抗生素给药剂量和给药途径 了解当地耐药谱 根据细菌学结果调整抗生素（降阶梯） 正确的疗程,VAP: 8 Day vs. 15 Day Antibiotic Therapy Shorter may be Better,% or Days,Primary Outcomes,(Chastre J et al. JAMA 2003;290:2588-2598),18.4 d,15.3 d,*P=.01,18.8,17.2,28.9,26,40.6,28.9,57.1,76.2,2019/1/24,Dr.HU Bijie,49,Thank you!,