e吸科耐药革兰阴性杆菌与治疗策略.pptx

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1、2023/2/21Dr.HU Bijie1CAP:OutpatientPreviously HealthyNo recent antibiotic therapy:A macrolidea or doxycyclineRecent antibiotic therapy:A respiratory fluoroquinolone(RFQ)alone,an advanced macrolide(AM)plus high-dose amoxicillin or AM plus high-dose amoxicillin-clavulanateComorbidities(COPD,Diabetes,R

2、enal or Congestive Heart Failure,or Malignancy)No recent antibiotic therapy:AM or RFQRecent antibiotic therapy:RFQ alone or AM plus a B-lactamSuspected aspiration with infection:Amoxicillin-clavulanate or clindamycinInfluenza with bacterial superinfection:B-lactam or a RFQ第1页/共31页2023/2/21Dr.HU Biji

3、e2CAP:InpatientMedical WardNo recent antibiotic therapy:RFQ alone or AM plus B-lactamRecent antibiotic therapy:AM plus B-lactam or RF alone(regimen selected will depend on nature of recent antibiotic therapy)Intensive Care Unit(ICU)Pseudomonas infection is not an issue:B-lactam plus either AM or RFQ

4、Pseudomonas infection is not an issue but patient has B-lactam allergy:RFQ,with or without clindamycinPseudomonas infection is an issue:Either(1)an antipseudomonal agent plus ciprofluoxacin,or(2)an antipseudomonal agent plus an aminoglycoside plus RFQ or a macrolidePseudomonas infection is an issue

5、but patient has a-lactam allergy:the Either(1)aztreonam plus levofluoxacin or(2)aztreonam plus moxifluoxacin or gatifluoxacin,with or without an aminoglycoside Nursing HomeReceiving treatment in nursing home:RFQ alone or amoxicillin-clavulanate plus AMHospitalized:Same as for medical ward and ICU第2页

6、/共31页2023/2/21Dr.HU Bijie3NNIS报告的医院内肺炎病原体病原体检出率检出率排位排位8082(15331)9096(13433)80829096枸橼酸菌枸橼酸菌111111肠杆菌肠杆菌91143大肠杆菌大肠杆菌8456肺炎杆菌肺炎杆菌10834其他克雷伯其他克雷伯41811奇异变形杆菌奇异变形杆菌5268其他变形杆菌其他变形杆菌001413粘质沙雷菌粘质沙雷菌4377其他沙雷菌其他沙雷菌101213肠杆菌科合计肠杆菌科合计4230绿脓杆菌绿脓杆菌131722金葡菌金葡菌131911CoNS12138肠球菌肠球菌22108念珠菌念珠菌3595其他其他2625第3页/共31

7、页2023/2/21Dr.HU Bijie4铜绿假单胞菌、肺炎克雷伯菌和鲍曼不动杆菌是HAP常见的革兰阴性杆菌Antimicrob Agents Chemother.2003 Nov;47(11):3442-7第4页/共31页2023/2/21Dr.HU Bijie5Nosocomial tracheobronchitis in MV patients:incidence,aetiology and outcomeSurgical Medical Patients n 36 165 Gram-negative microorganisms 34(77.2)162(78.7)Pseudomona

8、s aeruginosa 14(31.8)58(28)Acinetobacter baumannii 6(13.6)55(26.5)Klebsiella spp.4(9.0)6(2.8)Enterobacter aerogenes 3(6.8)4(1.9)Serratia spp.2(4.5)11(5.3)Stenotrophomonas maltophilia 2(4.5)7(3.3)Escherichia coli 1(2.2)8(3.8)Haemophilus influenzae 0 4(1.9)Other 2(4.5)9(4.3)Gram-positive microorganism

9、s 10(22.7)45(21.7)MRSA 7(15.9)31(14.9)MSSA 2(4.5)6(2.8)Streptococcus pneumoniae 1(2.2)8(3.8)Eur Respir J 2002;20:14831489.第5页/共31页2023/2/21Dr.HU Bijie6 医院内肺炎病原菌（Meta分析，全国19901998年，6062株菌）病原体病原体菌株菌株构成构成绿脓杆菌绿脓杆菌124120.6克雷伯菌克雷伯菌60810.1大肠杆菌大肠杆菌3565.9肠杆菌属肠杆菌属2784.6不动杆菌不动杆菌2754.6嗜麦芽窄食单胞嗜麦芽窄食单胞1001.7流感嗜血杆菌

10、流感嗜血杆菌500.8金黄色葡萄球菌金黄色葡萄球菌3585.9肠球菌肠球菌831.4肺炎链球菌肺炎链球菌611.0第6页/共31页2023/2/21Dr.HU Bijie7病原菌病原菌发生类型发生类型株数株数%早发性早发性晚发性晚发性鲍曼不动杆菌鲍曼不动杆菌1121318.6铜绿假单胞菌铜绿假单胞菌1101115.7金黄色葡萄球菌金黄色葡萄球菌36912.9大肠埃希菌大肠埃希菌0557.1阴沟肠杆菌阴沟肠杆菌1457.1肺炎克雷伯菌肺炎克雷伯菌1345.7粘质沙雷菌粘质沙雷菌0445.7念珠菌念珠菌1345.7嗜麦芽窄食单胞嗜麦芽窄食单胞0334.3变形杆菌变形杆菌0334.3表皮葡萄球菌表皮

11、葡萄球菌1122.9肠球菌肠球菌1122.9产碱杆菌产碱杆菌0222.9肺炎链球菌肺炎链球菌1011.4洛菲不动杆菌洛菲不动杆菌0111.4黄杆菌黄杆菌0111.4合计合计115970100.0 52例VAP病原分布(9901)第7页/共31页2023/2/21Dr.HU Bijie8NLRTI前五位病原菌在前五位病原菌在6个常见科室的比较个常见科室的比较 谢红梅，胡必杰，何礼贤，等.2819例医院下呼吸道感染病原和预后分析.上海医学2003；26：880-885第8页/共31页2023/2/21Dr.HU Bijie9医院内肺炎病原早期早期早期早期中期中期中期中期晚期晚期晚期晚期1 3 5

12、10 15 1 3 5 10 15 2020链球菌链球菌链球菌链球菌流感杆菌流感杆菌流感杆菌流感杆菌金葡菌金葡菌金葡菌金葡菌 MRSAMRSA肠杆菌肠杆菌肠杆菌肠杆菌肺克，大肠肺克，大肠肺克，大肠肺克，大肠绿脓杆菌绿脓杆菌绿脓杆菌绿脓杆菌不动杆菌不动杆菌不动杆菌不动杆菌嗜麦芽窄食单胞菌嗜麦芽窄食单胞菌嗜麦芽窄食单胞菌嗜麦芽窄食单胞菌入院天数入院天数入院天数入院天数第9页/共31页2023/2/21Dr.HU Bijie10呼吸科常见耐药革兰阴性杆菌肺炎克雷伯杆菌，大肠埃希菌肠杆菌属，沙雷菌，枸橼酸菌，变形杆菌铜绿假单胞菌，其他假单胞菌鲍曼不动杆菌，其他不动杆菌嗜麦芽窄食单胞菌属伯克霍尔德菌属产

13、碱杆菌属，黄杆菌属NPRS结果显示，铜绿和鲍曼作为MDR问题正在凸现第10页/共31页2023/2/21Dr.HU Bijie11细菌耐药是否会影响病死率?治疗肺炎杆菌ESBL菌株血液感染(n=31)合适治疗(n=19)病死率 5%不恰当治疗(n=12)病死率 42%P=0.02Source:Schiappa et al JID 1996;74:529-36第11页/共31页2023/2/21Dr.HU Bijie12第12页/共31页2023/2/21Dr.HU Bijie13在在ICUICU中肺部感染耐药菌问题尤为突出中肺部感染耐药菌问题尤为突出第13页/共31页2023/2/21Dr.H

14、U Bijie14MDR引起肺炎的防治策略预防医院内肺炎（HAPHAP、VAPVAP、HCAPHCAP）早期、准确的病原学诊断，不要治疗定植菌和污染菌停止无效、耐药的抗生素，避免更严重的后果加大剂量：从药敏单中寻找中介（低敏）的药物联合使用，在安全范围内的最大剂量，时间依赖性的药在允许范围缩短用药间隔，甚至24h24h连续点滴旧药新用：多粘菌素E E，舒巴坦对不动杆菌等联合用药：MICMIC为16ug/ml16ug/ml的头孢他啶和16ug/ml16ug/ml的阿米卡星合用可能有效；特门汀与氨曲南联合治不发酵糖菌效果有时很好；氨曲南可耐受金属酶第14页/共31页2023/2/21Dr.HU B

15、ijie15Managing Infection In The Critical Care Unit:How Can Infection Control Make The ICU Safe?Crit Care Clin.2005 Jan;21(1):111-28 Shulman L,Ost DDivision of Pulmonary and Critical Care Medicine,North Shore University Hospital,Manhasset,NY 11030,USA第15页/共31页2023/2/21Dr.HU Bijie16VAP预防方法的有效性评价Route

16、of intubationSearch for sinusitisCircuit changesHumidifierHumidifier changesEndotracheal suctioningSubglottic secretion drainageChest physiotherapyTracheostomyKinetic bedsSemi-recumbent positionProne positionStress ulcer prophylaxisProphylactic antibiotics第16页/共31页2023/2/21Dr.HU Bijie17第17页/共31页2023

17、/2/21Dr.HU Bijie18Antiseptic impregnated endotracheal tubes for the prevention of bacterial colonization在实验室气道模型中建立不同对MRSA,PA,AB 和产气肠杆菌有抗菌作用的气管插管(ETTs)，包裹有洗必泰和碳酸银抗菌ETT和对照 ETT(未包裹）用浓度108cfu/ml的菌液污染，5天孵育，管腔的远端和近端分别采样细菌培养抗菌ETT细菌定植量为1-100 cfu/管，而对照ETT达106cfu/管(P 24 hrs.INTERVENTIONS:Patients were random

18、ized into two groups;one group was suctioned with CS and another group with the OS.MEASUREMENTS:Throat swabs were taken at admission and twice a week until discharge to classify pneumonia in endogenous and exogenous.MAIN RESULTS:A total of 443 pts(210 with CS,233 with OS)were included.There were no

19、significant differences between groups of patients in age,sex,diagnosis groups,mortality,number of aspirations per day,and APCHE II score.No significant differences:in percentage of pts who developed VAP(20.47%vs.18.02%);in the number of VAP cases per 1000 MVDs(17.59 vs.15.84);in the VAP incidence b

20、y MV duration;in the incidence of exogenous VAP;in the microorganisms responsible for pneumonia.Patient cost per day for the CS was more expensive than the OS(11.11 US dollars+/-2.25 US dollars vs.2.50 US dollars+/-1.12 US dollars,p .001).结论:闭合痰液吸引系统不能降低VAP发病率，包括外源性肺炎Crit Care Med.2005 Jan;33(1):115

21、-9第20页/共31页2023/2/21Dr.HU Bijie21Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia:a role for routine endotracheal aspirate cultures方法：299需要机械通气至少48 h的病例，每周两次采集气管内吸引物（EA）定量培养。发生VAP后用 BAL培养确定病原体，并与EA结果进行比较。最后有75例诊断VAP，41例BAL培养阳性，先前常规EA培养中有34例(83%)阳性，1例早发肺炎发生VAP时还没有采集EA；4例结果

22、不一致但抗菌药物选用合适，2例选用药物有延迟结论：每周两次常规EA培养对早期正确选用VAP治疗抗菌药物是合适的Chest.2005 Feb;127(2):589-97第21页/共31页2023/2/21Dr.HU Bijie22Blind and bronchoscopic sampling methods in suspected VAP-A multicentre prospective study.OBJECTIVE:To compare 4 sampling methods:blind tracheal aspirate(blind TA),blind protected telesc

23、oping catheter(blind PTC),bronchoscopic PTC and bronchoscopic BAL,for diagnosis of VAP.DESIGN&SETTING:Prospective multicentre study.Five ICU in France.PATIENTS:63 pts with MV for more than 48 h,no recent antibiotic change(72 h)and suspected nosocomial pneumonia.INTERVENTIONS:All patients underwent t

24、he four sampling methods.Direct examination and quantitative cultures of the four specimens were performed.MEASUREMENTS AND RESULTS:Visible secretions expelled from the catheter were present 40 times(63%)for blind PTC and 45 times(71%)for bronchoscopic PTC.After exclusion of 11 uncertain cases,34 VA

25、P were diagnosed.Direct examination of PTC(either blind or bronchoscopic)did not differ from direct examination of bronchoscopic BAL in predicting VAP diagnosis and in guiding initial antibiotic treatment correctly.Compared to that of bronchoscopic BAL(0.98),the area under receiver operating charact

26、eristics(ROC)curve was smaller for blind TA(0.78,p=0.002),blind PTC(0.83,p=0.009)and bronchoscopic PTC(0.85,p=0.01).When samples with visible secretions expelled from the catheter were considered,blind and bronchoscopic PTC had areas under ROC curve close to that of bronchoscopic BAL(0.90,p=0.22 and

27、 0.91,p=0.27,respectively).CONCLUSIONS:Blind PTC appears to be a good alternative to bronchoscopic sampling for VAP diagnosis,provided that the sample contains visible secretions expelled from the catheter.Intensive Care Med.2004 Jul;30(7):1319-26第22页/共31页2023/2/21Dr.HU Bijie23Combination therapy wi

28、th polymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infectionsBACKGROUND:The treatment of infections caused by multidrug-resistant(MDR)Gram-negative organisms poses a therapeutic challenge.The use of polymyxin B has been resurrected specifically for this purpose.P

29、ATIENTS AND METHODS:We retrospectively reviewed the clinical and microbiological efficacy,and safety profile of polymyxin B in the treatment of MDR Gram-negative bacterial infections of the respiratory tract.Twenty-five critically ill patients received a total of 29 courses of polymyxin B administer

30、ed in combination with another antimicrobial agent.RESULTS:Patients were treated with intravenous,and/or aerosolized polymyxin B.Mean duration of polymyxin B therapy was 19 days(range 2-57 days).End of treatment mortality was 21%,and overall mortality at discharge was 48%.Nephrotoxicity was observed

31、 in three patients(10%)and did not result in discontinuation of therapy.CONCLUSIONS:Polymyxin B in combination with other antimicrobials can be considered a reasonable and safe treatment option for MDR Gram-negative respiratory tract infections in the setting of limited therapeutic options.J Antimic

32、rob Chemother.2004 Aug;54(2):566-9第23页/共31页2023/2/21Dr.HU Bijie24铜绿假单胞菌Pseudomonas aeruginosa第24页/共31页2023/2/21Dr.HU Bijie25A 7-year study of severe hospital-acquired pneumonia requiring ICU admission在1616张和2020张内科-外科ICUICU中，连续观察需要入住ICUICU的重症HAPHAP，共7 7年。9696次重症HAPHAP中，GNBGNB占5151，PAPA最常见（2424）。5151

33、例（5353）死亡，曲菌和PAPA引起的肺炎病死率最高。感染性休克(OR:14.27)(OR:14.27)和COPD(OR:6.11)COPD(OR:6.11)是影响预后的独立危险因素。Intensive Care Med.2003 Nov;29(11):1981-8第25页/共31页2023/2/21Dr.HU Bijie26鲍曼不动杆菌Acinetobacter baumannii第26页/共31页2023/2/21Dr.HU Bijie27Effect from multiple episodes of inadequate empiric antibiotic therapy for

34、ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patientsBACKGROUND:The purpose of this retrospective study was to determine the effect of inadequate empiric antibiotic therapy(IEAT)on the outcome for adult trauma patients with VAP.METHODS:This study enrolled 82

35、 patients with multiple VAP episodes(200 VAP episodes;mean 2.4;range 2-5).An episode of IEAT was a VAP episode with empiric therapy having no in vitro activity against causative bacteria.There were 78(39%)IEAT episodes involving 54 patients.Most often,IEAT was attributable to the presence of Acineto

36、bacter spp,Stenotrophomonas maltophilia,or Alcaligenes xylosoxidans.All the patients received appropriate definitive therapy according to the final culture.The patients were classified by number of IEAT episodes:0(n=28),1(n=34),and more than 1(n=20).RESULTS:Demographics and injury severity were simi

37、lar among the groups.The mortality rate was 3.6%for no episodes,8.8%for one episode,and 45%for more than one episode(p 0.001).On the basis of multiple logistic regression,experiencing multiple IEAT episodes was independently associated with the risk of death(odds ratio,4.28;95%confidence interval,1.

38、44-12.71).Additionally,experiencing multiple IEAT episodes was associated with prolonged intensive care unit stay(p=0.007)and prolonged mechanical ventilation(p=0.005).CONCLUSIONS:Critically ill trauma patients experiencing multiple episodes of IEAT for VAP have increased morbidity and mortality.The

39、se findings reinforce the importance of developing and refining a unit-specific pathway for the empiric management of VAP.J Trauma.2005 Jan;58(1):94-101第27页/共31页2023/2/21Dr.HU Bijie28鲍曼不动杆菌泛耐株的治疗Treatment of pan-drug resistant Acinetobacter baumannii方法：89例PDRAB感染用不同方案治疗：A组(n=39)：carbapenem sulbactam

40、；B组(n=30)：2/3 代cephalosporins,antipseudomonas penicillins,or fluoroquinolones+aminoglycosides 结果：两组临床结果无差异：感染吸收(25/59,42%vs 12/30,40%)或存活(35/59,59%vs 17/30,57%)。但48株细菌中有16株对imipenem/sulbactam敏感，单独对imipenem敏感仅2株；8株对meropenem/sulbactam敏感，单独对meropenem敏感仅3株结论：carbapenem-sulbactam合用不能明确是否可提高临床效果，但可降低 PDR

41、AB菌株的MIC，早期用药可能对防治PDRAB有价值Scand J Infect Dis.2005;37(3):195-9第28页/共31页2023/2/21Dr.HU Bijie29Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections评价多粘菌素E和利福平联合应用对MDR铜绿假单胞菌的抗菌活性在7株试验细菌中有6株有协同作用，使MIC下降达到治疗水平。在4例难治的由MDR铜绿引起的临床病例(sepsis 或肺炎)中均获得成功治疗结论：微生物和临床观察发现多粘菌素E和利福平有协同作用，可用于难治性耐多药铜绿假单胞菌的治疗J Chemother.2004 Jun;16(3):282-7第29页/共31页2023/2/21Dr.HU Bijie30第30页/共31页2023/2/21Dr.HU Bijie31感谢您的观看！第31页/共31页