医院获得性感染肺炎防治进展(杨毅)

1、医院获得性感染医院获得性感染/肺炎肺炎防治进展防治进展内容提要HAP流行病学和MDR在ICU的重要性HAP的机制与MDR的危险因素HAP的诊断HAP的非抗生素预防策略HAP的抗生素治疗策略早期的有效的经验性治疗降阶梯策略MDR耐药的预防3定义Hospital-acquired pneumonia (HAP)入院48h后Ventilator-associated pneumonia (VAP)插管 4872hHealthcare-associated pneumonia (HCAP)Any patient出现感染的90天内在ICU住院2天以上Resided in a nursing home R

2、eceived recent iv antibiotic, chemotherapy or wound care last 30 daysAttended a hospital or hemodialysis clinicATS. Am J Respir Crit Care Med 2005;171:388流行病学高发病率-最常见的院内感染之一(第二位) 5-15 cases / 1000 admissions6 to 20 fold higher in MV patients25% of all ICU infections50% of all antibiotics prescribed常

3、见病原菌 - Aerobic gram-negative bacilli P. aeruginosa、K. pneumoniae、Acinetobacter spp. - Gram-positive ： MRSA - Anaerobes are uncommonAm J Respir Crit Care, 2002;165:867MMWR Recomm Rep, 2004;53(RR-3):1-36Extra-ICU/hosp stay NP/VAP: ICU stay increased 3 fold 10 32 d additional hosp stay 9.2 d of additio

4、nal hospital stay Median length of ICU stay for VAP 21 d vs 15 d for control pat Fagon et al. Am J Med1993, 94:281-288. Jimenez et al. Crit Care Med 1989, 17:882-885. Leu et al. Am J Epidemiol 1989, 129:1258-1267VAP对患者医疗费用和预后的影响P0.001J Rello et al Epidemiology & outcomes of VAP in a large US dat

5、abase.(MediQual-Profile database by CIC) Chest 122:2115-21, Dec. 2002高病死率高病死率 33-50% attributable mortalityMDR infectionMDRMulti-Drug-resistanceG-菌对四类抗生素中3/4类耐药Ceftazidine, Ciprofloxacin, Gentamicin, ImipenemPseudomonas aeruginosa Acinetobacter speciesESBLs/AmpCCOS, CCOS PDR G+MRSAG-杆菌耐药对预后的影响Prospe

6、ctive cohort study.Dec 1996 to Sep 2000 Inpatient surgical wards at a university hospN=924 pats with GNR infectionsOutcomes were compared between GNR infections with and without antibiotic resrGNRs: resistant to one or more of the followingall aminoglycosides, including amikacinall cephalosporinsall

7、 carbapenemsall fluoroquinolonesCrit Care Med 2003; 31:10351041rGNR:入住ICUMVCRRT抗生素更换住院时间病死率治疗过程中铜绿假单胞产生耐药-病死率明显增加N=489 pats with NP耐药：对PIP, CFZ, IMP, CIP至少1个耐药入组时耐药 n=144治疗过程中(14d)出现耐药 n=30Mortality:敏感组 7.5% vs 耐药组 7.6% (p=0.96, RR0.94)治疗过程持续敏感组 6.3% vs 新耐药组 26.6% (p=0.03, RR 2.9)继发性菌血症治疗过程持续敏感组 1.4

8、% vs 新耐药组 14% (p0.050.04环境和手主要为G+菌Hand of Pat Hand of staffG+ highhighG- lowlowColonization AspirationHAPMRSA*l传播途径：传播途径： n误吸最重要的误吸最重要的NP/VAPNP/VAP的原因的原因n经空气和血源性感染并不常见经空气和血源性感染并不常见发病机理发病机理MDR危险因素-MV和既往抗生素应用135 episodes in ICUAm J Respir Crit Care Med. 1998;157:531VariableORPMV7d6.0.009Prior ABs13.51

9、03 CFU/ml)bronchoalveolar lavage (104 CFU/ml)endotracheal aspirate (106 CFU/ml)Antibiotic use more appropriate、accurateImproved survival Baughman RP. Chest. 2000;117:203SFagon JY,et al. Ann Intern Med 2000;132:621Cook D, et al. Chest. 2000;117:195S非抗生素治疗策略非抗生素治疗策略l气管插管与机械通气气管插管与机械通气n插管路径插管路径nNIV/IVN

10、IV/IVn气囊的管理气囊的管理n声门下的积液声门下的积液n湿化与雾化湿化与雾化n管路与冷凝水管路与冷凝水nMVMV时间时间n误吸误吸/ /体位体位n体位体位/ /胃肠道返流胃肠道返流n营养途径营养途径l口鼻咽腔口鼻咽腔/ /肠道定植肠道定植l溃疡预防溃疡预防/ /血糖控制血糖控制lICUICU的医疗强度的医疗强度A. 一般预防措施-Hand washing漂白粉消毒手漂白粉消毒手Ignaz Philipp Semmelweis(1818-1865)Hand washing -important underused measure to prevent NPNOW消毒剂对手部细菌的清除作用消毒

11、剂对手部细菌的清除作用99.9 3.099.0 2.090.0 1.00.0 0.0含有乙醇的刷手液含有乙醇的刷手液（70%异丙醇）异丙醇）抗菌肥皂抗菌肥皂（4%洗必太）洗必太）普通肥皂普通肥皂杀灭细菌比例杀灭细菌比例% log0180分钟分钟60消毒后时间消毒后时间Hosp Epidemiol Infect Control, 2nd Edition, 1999. qThe use of protective gowns and gloves during patient contact can not be recommended for the routine prevention of

12、VAPqMust be considered When handling respiratory secretionsDuring patient contact when the patient carries an MDR pathogen (MRSA)B.气管插管与机械通气(1)缩短MV时间Rello J. Crit Care Med 2003; 31:2544 2551Ibrahim EH et al. Chest 2001，120:555-61Casecontrol study in FranceN=50 pats with COPD exacerbation and cardiog

13、enic pul edemaJAMA 2000, 284:2361-2367.气管插管与机械通气(2)提倡NIV-COPD exacerbation and cardiogenic edemaNIVMVPMV时时间间6d10d0.01LOS of ICU 9d15d0.02Rouby JJ, et al. Am J Respir Crit Care Med. 150: 776783经鼻经鼻/口插管后口插管后1周鼻窦炎和周鼻窦炎和VAP患病率患病率气管插管与机械通气(3)避免经鼻插管 Am J Respir Crit Care Med 1995, 152:137Case-match study

14、n=40Previous duration of MV =2d 气管插管与机械通气(4)避免再插管Re-intubationControlsPNP/%47%10%0.001Mortality Total35%20%0.14 Related17.5%0%0.01ICU stay/d19+/-1014+/1248h气管插管与机械通气(8)呼吸机管路的更换频率呼吸机管路的更换频率Ventilator circuit changeq48hNoPVAP31.4%28.6%0.8Duration of MV10.1d9.1d0.7Mortality17.1%25%0.4Deaths with VAP8.6

15、%7.1%0.8频繁更换呼吸机管路对预防频繁更换呼吸机管路对预防VAP并无益处并无益处37nHEM reduced hosp-, not community-acquired VAPnHEM reduced ICU staynHEM reduced circuit cost Kirton OC. Chest 1997, 112:1055-1059.气管插管与机械通气(9) 湿化与HMEAspiration pattern: time dependent for prone positionTorres AT. Ann Inter Med, 1992, 116: 540C. 误吸/体位与营养(1

16、)体位与误吸Multicenter, prospective, randomized, single-blind studyEnteral nutrition started in 101 pats during first 36hNasogastric tube vs nasogastrojejunal tubeResults:Gastrointestinal complications: 57% vs 25% P48hqSucralfate 1g/6h in 604 patients qIV ranitidine 50mg/8h in 596 patients P221umol/L96(1

17、2.3%)69(9%)BUN19.2mmol/L88(11.2%)59(7.7%)RRT64(8.2%)37(4.8%)ICU5d20.2%10.6%Bloodstream infection (n)6132 (P10 ds (n)13486(P5 days) or risk factors for MDR PathogensNoYesLimited Spectrum TherapyBroad SpectrumTherapy for MDR PathogensATS. Am J Respir Crit Care Med. 2005, 171: 388-416HAP经验性抗生素的选择经验性抗生素

18、的选择47低危MDR感染患者的抗生素选择Potential PathogenStreptococcus pneumoniaeHaemophilus influenzaeMethicillin-sensitive Staphylococcus aureusEnteric gram-negative bacilli(Antibiotic sensitive) Enterobacter species Escherichia coli Klebsiella species Proteus species Serratia marcescensRecommended Antibiotic Ceftri

19、axone or Levofloxacin or Moxifloxacin or Ciprofloxacin or Ampicillin/sulbactam or ErtapenemATS. Am J Respir Crit Care Med. 2005, 171: 388-41648Potential PathogensP. aeruginosaESBL (+) K. pneumoniaeAcinetobacter speciesMRSAL. pneumophilaTherapyAntipseudomonal cephalosporin(cefepime, ceftazidime) orAn

20、tipseudomonal carbapenem(İmipenem, meropenem) orPiperacillin-tazobactam plusCiprofloxacin or levofloxacin orAminoglycosideLinezolid or vancomycinATS. Am J Respir Crit Care Med. 2005, 171: 388-416高危MDR感染患者的抗生素选择49起始经验治疗晚发型或具有起始经验治疗晚发型或具有MDRMDR病原菌病原菌危险因素的危险因素的HAPHAP、VAPVAP和和HCAPHCAP患者和所有患者和所有重症感染重症感染患

21、者患者MDR病原菌抗生素*联合治疗铜绿假单胞菌肺炎克雷伯菌（ESBL+）不动杆菌属抗假单胞菌头孢菌素（头孢他啶、头孢吡肟）或抗假单胞菌碳青霉烯类（亚胺培南、美罗培南）或-内酰胺/-内酰胺酶抑制剂（哌拉西林-他唑巴坦）加抗假单胞菌氟喹诺酮类（环丙沙星或左氧氟沙星）或氨基糖苷类（阿米卡星、庆大霉素或妥布霉素）*抗菌活性范围、抗生素的有效剂量、药动学特性、各种抗菌药物的 不良反应和单药治疗的作用都经过委员会的仔细审核50l评价de-escalation在VAP抗生素治疗中的意义前瞻性观察性研究(43m)MICU and SICU115 pats with VAPl121 次VAP抗生素改变 56.2

22、%, deescalation抗生素改变的主要原因,占31.4% ICU- mortality 32.2%不合适起始抗生素 9%, 增加14.4%病死率Crit Care Med 2004; 32:2183219051抗生素轮换抗生素轮换Strategy of antibiotic rotation Pellegrin University Hospital, France Medical ICU: 16 beds Time: 7 years study 2856 pats with MV-VAP (early/late onset) Period:1: 1995-1996 对照对照2: 19

23、97-1998 阶段轮换阶段阶段轮换阶段3: 1999-2001 扩大样本轮换扩大样本轮换 Rotation: 1 monthsCCM 2003, 31(7): 1908-1452Cycling in the Management of ResistancelCycling protocols (cefepime, pip/tazobactam, IMP, ticarcillin-clavulanic, 可合用Amk/Tob/Net, 限制Cipro等) at 1 month intervals in a MICUlOutcome: resistance in G- and incidence of VAPlBefore period (1995-1996): n=1044/After period (1997-998): n=1022 patients with MV