下呼吸道感染的诊治进展(同名0)课件

1、下呼吸道感染的诊治进展北京大学第一医院呼吸内科 王广发Pathogens of LRT Infection细菌 需氧G+球菌 需氧G-杆菌 厌氧菌病毒真菌支原体立克次体衣原体原虫Pneumocystis carinii Ten Leading Causes of Death, United States, 20191 Heart disease 726,974 2 Malignant neoplasms 539,577 3 Cerebrovascular 159,791 4 Bronchitis, Emphysema, Asthma 109,029 5 Unintentional injury

2、 and adverse effects 95,644 6 Pneumonia & Influenza 86,449 7 Diabetes 62,636 8 Suicide 30,535 9 Nephritis 25,331 10 Liver disease 25,175 National Center for Health Statistics (NCHS) Vital Statistics SystemGilbert, K and Fine, MJ (1994). Semin Respir Infect 9(3):140-52 Deaths per 100,000Pneumonia mor

3、tality rates per 100,000 patients in the United States from 1900-19900204060801001201401601802001900191019201930194019501960197019801990Lack of effective therapy; increase in mortalityCommunity Acquired PneumoniaMortalityChanges of hosts in recent years人口老龄化低免疫人群的不断增加肾上腺皮质激素、免疫抑制剂降低了宿主免疫功能有创医疗技术广泛应用

4、增加了细菌入侵的途径某些疾病的日益增多糖尿病、AIDSChanges of Pathogens in Bacterial Pneumonia病原的多样化革兰氏阴性杆菌性肺炎日益多见原先认为不致病的微生物发现具有致病性新病原的出现-军团菌细菌耐药成为日益普遍的现象(MRSA,ESBL) 细菌耐药甲氧西林耐药的金黄色葡萄球菌（MRSA）甲氧西林耐药的表皮葡萄球菌（MRSE）万古霉素中度敏感的金葡菌 （VISA）万古霉素耐药的肠球菌（VRE）青霉素耐药的肺炎链球菌（ PRSP）超广谱-内酰胺酶 （ESBLs）AmpC碳青霉烯酶多重耐药菌的分离率 2019年 NNIS调查资料与1994年资料的比较万古

5、霉素耐药肠球菌：从15% 到 26%甲氧西林耐药金黄色葡萄球菌：从38%到55%克雷伯菌对三代头孢菌素的耐药率：从7% 到9%铜绿假单胞菌对亚胺培南的耐药率：从12%到19%铜绿假单胞菌对喹诺酮类耐药率：从12%到23%肠杆菌属细菌对三代头孢菌素的耐药率：从34%到 37%获得性细菌耐药直接从另一株细菌获得耐药质粒，质粒上携带有耐药基因通过病毒转染从其他细菌获得耐药基因染色体突变从死细菌中获得DNA万古霉素耐药的肠球菌万古霉素的用量万古霉素的用量Kg耐药率%产 ESBL菌株分离率的地区差异 (2019 - 2000)051015202530354045澳大利亚日本台湾中国香港菲律宾新加坡大肠杆

6、菌肺炎克雷伯杆菌南非SENTRYESBL 阳性百分比产 ESBL 的地区差异 (2019-2000) 0102030405060阴沟肠杆菌粘质沙雷杆菌澳大利亚日本台湾中国香港菲律宾新加坡南非SENTRYESBL 阳性百分比在中国十家医院用E-test法评估六种广谱b-内酰胺药对分离细菌株的体外活性细菌 数 主要细菌 大肠埃希菌 107肠杆菌属 109 阴沟肠杆菌 克雷伯菌属 120 肺炎克雷伯菌 沙雷菌属 88 黏质沙雷菌 枸橼酸菌属 100 弗劳地枸橼酸菌吲哚阳性变形杆菌属 76 普通变形，摩根绿脓假单胞菌 100 不动杆菌属 99 鲍曼不动杆菌金黄色葡萄球菌(Oxs) 101凝固酶阴性葡萄

7、球菌 37 表皮葡萄球菌总计 937北京协和医院陈民钧教授等937株细菌对六种药物的总体敏感性排序 药物总体敏感率 亚胺培南96.5马斯平(头孢吡肟) 89.1头孢哌酮/舒巴坦85.8头孢他啶75.5头孢曲松66.9哌拉西林57.1北京协和医院陈民钧教授等北京协和医院陈民钧教授等药名耐药中介 MIC50 MIC90头孢吡肟17.011.0364头孢他啶 18.00.01.564头孢曲松50.047.0 32512 亚胺培南21.0 7.0332头孢哌酮/舒巴坦17.0 11.0464哌拉西林 23.0 0.0 8 512六种抗微生物药对100株铜绿假单胞菌的活性细菌的进化与耐药inactiva

8、tionimpermeabilityeffluxABBy-passAltered target细菌对抗生素的耐药机制细胞内药物浓度降低 外排增多 四环素（tetA） 氟喹诺酮类（norA） 外膜通透性降低 内酰胺类（OmpF;OprD) 氟喹诺酮类（OmpF） 细胞膜运输能力降低 氨基糖甙类（低能量）药物失活 内酰胺类（ 内酰胺酶） 氨基糖甙类（修饰酶） 磷霉素（谷胱甘肽结合） 氯霉素（灭活酶）靶位修饰 氟喹诺酮类（旋转酶修饰） 利福平（DNA聚合酶结合） 内酰胺类（PBP改变） 大环内酯类（rRNA甲基化）靶位旁路 糖肽类（vanA、vanB） 甲氧苄定（胸腺嘧啶缺陷株）内酰胺酶的分类（1）

9、1973年 Richmond & Sykes：酶作用底物、是否被邻氯西林抑制 、1976年Matthew&Harris：等电聚焦法、等电点 质粒介导酶: TEM、SHV、HMS、PSE、OXA 染色体介导酶：K1、D31、P991978年Ambler&Scott：氨基酸序列分析 A、B、C、D内酰胺酶分类（2）1981年Mitsuhashi & Inoue：酶作用底物 青霉素酶 Pcase(、） 头孢菌素酶 Case 头孢呋辛酶 Cxase1989年Bush K：作用底物、是否被CA抑制、酶产生菌及分离率（是否常见） Group 1,2,3,4内酰胺酶分类（3）Bush,Jacoby&Mede

10、iros(BJM，2019)Routs of Bacteria invading into the lung口咽部污染分泌物的误吸空气中细菌的吸入细菌血行播散临近组织直接侵入肺脏Predisposing Factors of lower respiratory tract infectionPathogenic diagnosis of LRT Infection痰涂片：简便、快捷 WBC25/LPF，鳞状上皮107/ml致病菌 细菌含量103cfu/mlBAL104cfu/mlPSB涂片敏感性20-100%特异性95-100%PSB的假阴性在肺炎早期采样取材部位未受累标本处理不当标本于抗生素

11、使用后采取后果 侵袭性方法临床常规方法 RRR (95% CI) NNT (CI) 病死率 16% 26% 37% (8.2 to 58) 11 (6 to 56) 差别(CI) 平均不用抗生素的天数 d 5.0 2.2 2.8 (1.9 to 3.6) 平均用抗生素数/d 1.2 1.5 0.3 (0.2 to 0.5) 纤维支气管镜PSB或BAL 指导治疗Fagon J-Y. Ann Intern Med. 2000 Apr 18;132:621-30 (P = 0.022)(P 0.001)(P 65 years25-44 per 1000/year 65 years (institut

12、ionalized)68-114 per 1000/yearHospitalizationGPs office17-35 %MortalityOverall1-3 %Hospitalized patients6-24 %Requiring ICU22-57 %Niederman, MS, et al (1986). Crit Care Clin. 2(3):471-95. Marrie, TJ (1994). Clin Infect Dis 18(4):501-13; Marrie TJ 9(2019). Infect Dis Clin North Am 2(3):723-4005101520

13、2530S. pneumoniaeC. pneumoniae*ViralM . pneumoniaeLegionella sp.H. influenzaeG-neg enterobacteriaC psittaciCoxiella burnetiiStaph aureusM. catarrhalisOtherData from 26 prospective studies (5961 adults) from 10 countries. * Data from six studies Woodhead, MA (2019)Community Acquired Pneumonia: Bacter

14、iology in Hospitalized PtsCommon pathogens associated with CAPHospitalized patientsAmbulatory patientsNon-ICUICU (severe)*Streptococcus pneumoniaeS pneumoniaeS pneumoniaeMycoplasma pneumoniaeM pneumoniaeH influenzaeHaemophilus influenzaeC pneumoniaeLegionellaChlamydia pneumoniaeH influenzaeGram-nega

15、tive bacilliVirusesLegionellaStaphylococcus aureus*Excluding Pneumocystis.File TM, Tan JS. Curr Opin Pulm Med. 2019;3:89-97. Streptococcus Pneumoniae为G（+）球菌，呼吸道寄生有多糖体荚膜（86种亚型）80%为1-8型多见,以1-3型最多,3型毒力最强不产生具有组织破坏作用的毒素不形成空洞右上叶后段肺炎Mortality of Pneumococcol Pneumonia in Pre-antibiotic and antibiotic eraS.

16、 pneumoniae: prevalence of penicillin- intermediate and -resistant strainsSW USA12% 28%NE USA10% 20%Brazil29% 1%Mexico27% 25%South Africa55% 25%Saudi Arabia44% 18%Hong Kong6% 74%pen-I (penicillin MIC 0.121 g/ml)pen-R (penicillin MIC 2 g/ml)The Alexander Project 2019, SmithKline Beecham data on fileU

17、K6% 8%Belgium6% 13%Spain10% 37%France17% 45%Germany1% 4%Poland5% 17%Switzerland3% 11%Italy7% 6%Portugal 13% 10%Czech Republic1% 2%Slovak Republic15% 15%S. pneumoniae: prevalence of penicillin- intermediate and -resistant strainspen-I (penicillin MIC 0.121 g/ml)pen-R (penicillin MIC 2 g/ml)The Alexan

18、der Project 2019, SmithKline Beecham data on filePenicillin Non-SusceptibleStreptococcus pneumoniae in the US% of isolates resistant to penicillin*Year*MIC 0.1 to 1.0 g/mL (intermediate) and 2.0 g/mL (high level) penicillin resistanceAppelbaum PC. Clin Infect Dis. 1992;15:77-83. Breiman RF, et al. J

19、AMA. 1994;271:1831-1835. Doern GV, et al. Antimicrob Agents Chemother. 2019;40:1208-1213. Thornsberry C, et al. Diagn Microbiol Infect Dis. 2019;29:249-257. Thornsberry C, et al. J Antimicrob Chemother. 2019;44:749-759.Thornsberry C, et al. In: Abstracts of the 39th ICAAC, 2019, abstract 820. Selman

20、, L. In: Abstracts of the 40th ICAAC, 2000, abstract 1789. Selman, L. In: Abstracts of the 40th ICAAC, 2000, abstract 1800. Selman, L. In: Abstracts of the 38th IDSA, 2000, abstract 201933. Data on file at Ortho-McNeil Pham.Streptococcus pneumoniae strains recovered from LRT with intermediate and hi

21、gh levels of resistanceDoern GV,Emerging Infectious Diseases 5(6), 2019. CDC多药耐药的肺炎链球菌常见耐药类型penicillin and TMP/SMX (6.9%)penicillin, macrolide, and chloramphenicol (4.6%)penicillin, macrolide, tetracycline, and TMP/SMX (3.6%)penicillin, macrolide, tetracycline, TMP/SMX, and chloramphenicol ( 5.4% )

22、Doern GV,Emerging Infectious Diseases 5(6), 2019. CDCThe prevalence of macrolide-resistant S. pneumoniae: 19922019Prevalence of macrolide resistance (erythro MIC 1 g/ml; %)YearFelmingham et al. J Chemother 2019;11:521The Alexander Project 2019/2019. Data available on request from SmithKline BeechamT

23、he Alexander Project 2019 (alexander-network)喹诺酮耐药的肺炎链球菌喹诺酮耐药逐渐增加 (cipro MIC 4 mg/L) 0% in 1993, 3.7% in 2019, 成人耐药的增多与氟喹诺酮类使用量相关 处方量每年0.8%增至5.5%(1988-2019)喹诺酮耐药存在差异: cipro levofloxacin sparfloxacin grepafloxacin trovafloxacin gatifloxacin moxifloxacin gemifloxacin42.9%对青霉素耐药的肺炎链球菌对环丙沙星也耐药中国5个城市肺炎链球

24、菌对6种抗生素的敏感率（MIC90）北 京 （N418）成 都（N42）沈 阳（N57）广 州（N36）上 海（N34）青霉素87.8（0.094）64.7（0.25）77.8（0.38）61.8（2）阿莫/克拉100（0.023）100（0.5）100（0.125）100（0.25）87.3（4）头孢呋肟97.8（0.19）100（0.25）94.7（0.5）93.7（0.38）67.6（4）头孢曲松99.1（0.064）94.7（0.25）91.8（0.125）82.4（1）头孢噻肟99.0（0.064）97.6（0.125）94.7（0.125）94.5（0.064）79.4（0.064

25、）万古霉素100.0（0.5）100（1）100（1）Penicillins Alteration in penicillin-binding proteins (PBPs) Cephalosporins Alterations in PBP2x, PBP1aMacrolides Efflux pump alteration (mef E) Ribosomal methylase (erm AM) Spontaneous mutations Fluoroquinolones Alterations in DNA gyrase (gyr A and gyr B) Alteration in to

26、poisomerase IV (par C and par E) Mechanisms of Antibiotic Resistance in S pneumoniae肺炎链球菌肺炎的治疗青霉素G为首选药物青霉素过敏者红霉素、洁霉素、一代头孢菌素对青霉素中中介（MIC0.1-2ug/ml） 加大剂量，每日600万单位。对青霉素高度耐药（MIC 2ug/ml）头孢曲松/头孢噻肟、新喹诺酮类、万古霉素，亚胺培南、万古霉素、壁霉素、利福平G-，含荚膜，营养条件要求高，在巧克力平板生长，根据荚膜分为A、B、C、D、E、F6个血清型，B型致病力最强也最常见感染率20%+发病机理：内毒素-致病过程有重要作

27、用 荚膜其有抗吞噬作用 菌毛粘附定植 IgA蛋白酶支气管肺炎，叶或段的浸润影、空洞、脓胸治疗：AM/CL, TMP/SMX, oral ceph2/3,Cefotaxime, Ceftriaxone、 IMP, MER, Ciprofloxacin流感嗜血杆菌(Haemophilus influenzae)H. influenzae Resistance Trust IV 2000 Abstracts of the 40th ICAAC, 2000, abstract 1800. Selman, L. In: Abstracts of the 38th IDSA, 2000, abstract

28、 201933Data on file Ortho-McNeil PharmaceuticalH. influenzaeIncreasing Beta Lactamase Production2019-2019年亚欧流感嗜血杆菌药敏检测Atypical PneumoniaThe term atypical pneumonia is commonly used to describe a form of pneumonia in which systemic symptoms are usually more pronounced than respiratory symptoms.Atypic

29、al Respiratory PathogensMycoplasma pneumoniaeLegionella speciesChlamydia pneumoniae Others:respiratory viruses, (influenza A and B, parainfluenza viruses, and respiratory syncytial virus), Chlamydia psittaci(鹦鹉热衣原体),and Coxiella burnetii(伯氏柯克斯体)Mycoplasma pneumoniae为能在无细胞培养基上生长的最小微生物，无细胞壁，结构简单，营养要求高

30、，生长需要胆固醇对四环素和大环内酯类敏感肺炎支原体能产生过氧化氢及超氧化物溶血素与呼吸道上皮粘附获取外源营养物质可以进入细胞内生长造成上皮细胞及其纤毛的损伤容易与其它病原同时感染宿主美国每年2百万例肺炎支原体感染其中约5%导致肺炎，相当于 2例/1000人口/年 约20%肺炎支原体的感染没有症状，多数呼吸道症状轻微肺炎支原体可以引起爆发流行（ a report by the Centers for Disease Control and Prevention of an outbreak in Colorado）Mycoplasma pneumoniae肺炎支原体(Mycoplasma pne

31、umoniae)年轻人及儿童多见，秋季发病多，潜伏期2-3周体温在37.8-39，可伴有头痛、肌痛病理以间质性炎症为主咳痰：少量粘液毯或干咳胸片多表现为斑片状，有时呈网状、云雾状、粟粒状或间质浸润WBC正常或轻度升高冷凝集试验补体依赖性抗体, 中耳炎, 溶血, 神经系统的损害-周围神经炎、脑膜炎、脊髓炎、神经根炎Erythromycin, Tetracycline疗程：7-10d支原体肺炎Cold Agglutinin Blood are collected in Wasserman tube containing NaEDTADefinite floccular agglutination

32、seen with unaided eye (upper panel)Disappears upon warming to 37 (bottom panel)Legionella Species革兰氏阴性杆菌、需氧、不产生芽孢、无荚膜军团菌超过40种 嗜肺军团杆菌（Legionella pneumophila）为主要多数军团菌肺炎（军团病）的病原 L. pneumophila: 15个血清型， 1型最常见L. pneumophila serogroup 1 可通过尿液检测抗原Dieterle stain of sputumLegionella被吞噬后，在呼吸道巨噬细胞胞体内繁殖释放细胞毒素杀死

33、吞噬细胞释放到细胞外在潮湿环境中繁殖，传播水源、空调器、雾化器污染中央空调系统可引发爆发流行危险因素：高龄、酗酒、吸烟、慢性疾病、器官移植死亡率：免疫功能正常者5-25%嗜肺军团杆菌(Legionella pneumophila)夏秋发病多，潜伏期2-10天，可伴有消化、神经系统症状、相对缓脉，临床分型流感样型（Pontiac fever）、肺炎型病理：融合的支气管肺炎伴小脓腔形成干咳或血丝痰，WBC1-2万培养方法：BCYE培养基或PCYE培养基抗体：间接荧光抗体大于等于1：128或恢复期血清大于等于1：256，两次抗体滴度增加4倍以上检测痰液、组织和尿中的抗原有重要的诊断价值BAL等的Gi

34、msa染色可以发现细菌并发症： Empyema, Cavitation, Endocarditis, Pericarditis, myositis, ARF红霉素每日2-4g，疗程：3wtrovafloxacin, levofloxacin, moxifloxacin and rifampicin X线特点：1、病变双侧、多发；2、进展迅速；3、多样性：大片、斑片、斑点结节状、条索、纱网状4、空洞出现快而闭合慢；5、炎症吸收慢嗜肺军团杆菌(Legionella pneumophila)军团菌肺炎入院日入院第3日入院第5日Chlamydia pneumoniae1986年首次发现为呼吸道病原预先

35、存在于细胞内An obligate, intracellular bacterium.双相生长周期在细胞内以网状体形式繁殖释放抗原到上皮表面引起炎症反应并导致纤毛运动障碍C. pneumoniae 缺乏细胞壁为成人及儿童肺炎的常见病原超过50%的成人曾有过感染Chlamydia pneumoniae并非终生免疫潜伏期：2-4周 症状通常轻微，也可病程迁延发热及咳嗽为常见的症状，胸部体检可有湿性罗音C. pneumoniae pneumonia: 双相病程 咽炎痊愈 1-3周后肺炎病死率 : 住院患者9.8%Chlamydial complement fixation antibody test

36、ing： IgM or IgG elevations that take a minimum of 2-3 weeks to rise after acute infection. Pneumonia of Mixed EtiologyAtypical pathogens frequently appear as mixed infections1/32/3 are likely coinfections, with S. pneumoniae the presence of at least one other pathogen in:33-64% of M. pneumoniae infe

37、ctions48-74% of C. pneumoniae infections54-63% of Legionella infections Treatment of Atypical pathogensSince C. pneumoniae and M. pneumoniae lack a peptidoglycan wall, -lactam antimicrobial agents are ineffective against them. C. pneumoniae and Legionella species can reside in or replicate within ce

38、lls, necessitating the use of antimicrobials that are active intracellularly.Suitable treatment options are macrolides, fluoroquinolones, or members of the new ketolide class of antimicrobials. Tetracyclines may be used to treat C. pneumoniae or M. pneumoniaeTreatment of CAPEmpiric therapy and patho

39、gen-directed therapyInitiation of prompt antimicrobial therapy is crucial to minimize morbidity, mortality, and health care costs. Antibiotic administration within 8 hours of hospital arrival has been associated with a lower 30-day mortality. Delaying antibiotic administration may increase complicat

40、ions or result in prolonged hospitalizations Community-Acquired Pneumonia (CAP) Year 2019Antibiotic Selection and Management UpdateEvaluation, Risk Stratification, and Current Antimicrobial Treatment Guidelinesfor Hospital-Based Management of CAP: Outcome-Effective Strategies Based onNew NCCLS Break

41、points and Recent Clinical Studies The ASCAP Panel* Consensus Report, 2019Antibiotic Selection for Community-Acquired PnuemoniaFactors Associated with an Increased Risk for Mortality of CAPIncreasing age(65)AlcoholismChronic lung diseaseImmunodeficiencySpecific laboratory abnormalities(azotemia and

42、hypoxemia)High Risk for Mortality(Radiograph)Bilateral effusionsModerate-size pleural effusionsMulti-lobar involvementBilateral infiltratesPatient characteristicsPointsDemographic factorsMaleAge (y)FemaleAge (y)- 10Nursing home resident10ComorbiditiesNeoplastic disease30Liver disease20Congestive HF1

43、0Cerebrovascular dis10Renal disease10Physical examination findingsAltered mental status20Respiratory rate 30 breaths/min20Systolic blood pressure 90 mm Hg20T 40C (104F)15Pulse rate 125 beats/min10Laboratory findingspH 10.7 mmol/L20Sodium 13.9 mmol/L10Hematocrit 30%10PO2 60 mm Hg*10Pleural effusion10

44、TotalPoint Scoring System for Prediction Rule(Pneumonia Severity Index, PSI)*Oxygen saturation 90% is also considered abnormal.Fine MJ et al. N Engl J MedClass IAge 50 y; no comorbidities;no abnormal physicalexamination findingsClass II 130 pointsRisk classification of patients with CAPMales ages ol

45、der than 70 years and females ages older than80 years would be assigned to ClassPatient ManagementOutpatient management Class&Brief inpatient observation Class Trditional hospitalization Class &重症肺炎(The Definition of ATS Guidelines)至少存在下列情况之一：呼吸频率大于 30次/分严重呼吸衰竭(PaO2/FIO2250)需要机械通气者双侧或多个叶的浸润阴影出现休克需要使

46、用升压药者少尿(尿量20ml/hour)98% in sensitivity and 32% in specificity for the need for ICUCAP year 2019 Antibiotic Selection and Management UpdateTable 1. ASCAP 2019 Guidelines Empiric Antimicrobial Therapy of Choice forOutpatient and In-Hospital Management of Patients with CAP (To be continued)CAP year 201

47、9 Antibiotic Selection and Management UpdateTable 1. ASCAP 2019 Guidelines Empiric Antimicrobial Therapy of Choice forOutpatient and In-Hospital Management of Patients with CAP (To be continued)Table 1. ASCAP 2019 Guidelines Empiric Antimicrobial Therapy of Choice forOutpatient and In-Hospital Manag

48、ement of Patients with CAPTable 1. ASCAP 2019 Guidelines Empiric Antimicrobial Therapy of Choice forOutpatient and In-Hospital Management of Patients with CAP医院获得性肺炎 Nosocomial pneumonia占全部医院获得性感染的15%（美国），中国为42-50%为医院获得性感染的第一位（中国），美国为第二位在非教学医院的发生率为每1000出院病人4.2人大学的附属医院为每1000出院病人7.7人死亡率高达25-50%医院获得性肺炎

49、的定义新出现的咳嗽咳痰肺部听诊出现异常胸片出现新的或不断进展的阴影伴有发热或低体温、白细胞增高病原：多种微生物感染住院或进入长期关护机构超过48小时或病人从医院出院1.5 mg/dL从其他病房转入ICU 有某些高危病原菌放射线检查双侧肺均有肺炎表现首次抗菌治疗不当年龄 60岁终末期基础疾病 休克初次治疗不当进展快的致死性基础疾病用过抗生素治疗 多系统器官衰竭非外科的主要诊断高危病原菌的迟发感染用升高pH的药物治疗预防肠道出血呼吸机相关性肺炎定义 气管插管或机械通气(MV)48小时后发生的肺炎称为呼吸机相关性肺炎(VAP)流行病学 占MV病人的 8-28% 气管插管病人接受MV，肺炎的危险性升高

50、 3-10 倍 死亡率为 24-50% 特殊基础情况或高危病原菌引起的肺部感染，病死率可高达 76%早发性和迟发性VAP 早发性VAP：在MV的前4天发病 迟发性VAP：MV5天或5天以上发病 两组VAP的常见病原菌不同 早发性VAP病人的预后较好VAP宿主的危险因素 血清白蛋白2.2g/dl 年龄60岁 ARDS COPD等肺脏疾病 神志障碍或昏迷 严重烧伤或创伤 器官衰竭 严重基础疾病 大量胃液吸入 上呼吸道定植 鼻窦炎VAP的医源性因素 H2受体拮抗剂制酸药 肌松药，持续静脉镇静 4单位的血液制品 颅内压力监测 MV2天 呼气末正压VAP的医源性因素 经常更换呼吸机管路 再次插管 鼻胃管 头部位置低平 转出ICU 以前用过抗生素或无抗生素治疗VAP和MV时间的危险性Fagon JY .Am Rev Respir Dis 1989;139(4):877-84抗生素 抗生素治疗对VAP有保护作用 2-3周后抗生素的保护作用消失 抗生素应用时间过长，容易筛选出耐药菌，导致耐药菌的定植抗生素的预防性应用只是延迟医院感染的发生，但同时使多重耐药菌二重感染的危险升高567 例病人接受 MV肺部感染前15天内接受抗生素治疗的病人发生VAP的危险性并未增高假单胞菌或不动杆菌属引起的肺炎： 抗生素治疗 65% 未用抗生素 19%Fagon JY .Am