1、 株洲市二医院株洲市二医院刘和平副主任医师e5吸科耐药革兰阴性杆菌与治疗策略CAP:Outpatient Previously Healthy No recent antibiotic therapy:A macrolidea or doxycycline Recent antibiotic therapy:A respiratory fluoroquinolone(RFQ)alone,an advanced macrolide(AM)plus high-dose amoxicillin or AM plus high-dose amoxicillin-clavulanate Comorbid
2、ities(COPD,Diabetes,Renal or Congestive Heart Failure,or Malignancy)No recent antibiotic therapy:AM or RFQ Recent antibiotic therapy:RFQ alone or AM plus a B-lactam Suspected aspiration with infection:Amoxicillin-clavulanate or clindamycin Influenza with bacterial superinfection:B-lactam or a RFQe5吸
3、科耐药革兰阴性杆菌与治疗策略CAP:Inpatient Medical Ward No recent antibiotic therapy:RFQ alone or AM plus B-lactam Recent 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 e
4、ither AM or RFQ Pseudomonas infection is not an issue but patient has B-lactam allergy:RFQ,with or without clindamycin Pseudomonas infection is an issue:Either(1)an antipseudomonal agent plus ciprofluoxacin,or(2)an antipseudomonal agent plus an aminoglycoside plus RFQ or a macrolide Pseudomonas infe
5、ction is an issue 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 Home Receiving treatment in nursing home:RFQ alone or amoxicillin-clavulanate plus AM Hospitalized:Same as for med
6、ical ward and ICUe5吸科耐药革兰阴性杆菌与治疗策略NNIS报报告告的的医医院院内内肺肺炎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359
7、5其他其他2625e5吸科耐药革兰阴性杆菌与治疗策略铜绿假单胞菌、肺炎克雷伯菌和鲍曼不动杆菌铜绿假单胞菌、肺炎克雷伯菌和鲍曼不动杆菌是是HAP常见的革兰阴性杆菌常见的革兰阴性杆菌Antimicrob Agents Chemother.2003 Nov;47(11):3442-7e5吸科耐药革兰阴性杆菌与治疗策略Nosocomial tracheobronchitis in MV patients:incidence,aetiology and outcomeSurgical Medical Patients n 36 165 Gram-negative microorganisms 34(77
8、.2)162(78.7)Pseudomonas 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-
9、positive microorganisms 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.e5吸科耐药革兰阴性杆菌与治疗策略 医院内肺炎病原菌医院内肺炎病原菌（Meta分析，全国分析，全国19901998年，年，6062株菌）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
10、.6嗜麦芽窄食单胞嗜麦芽窄食单胞1001.7流感嗜血杆菌流感嗜血杆菌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611.0e5吸科耐药革兰阴性杆菌与治疗策略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
11、杆菌0334.3表皮葡萄球菌表皮葡萄球菌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例例VAP病病原原分分布布(9901)e5吸科耐药革兰阴性杆菌与治疗策略NLRTI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；26：880-885e5吸科耐药革兰阴性杆菌与治疗策略医院内肺炎病原医院内肺炎病原e5吸科耐药革兰阴性杆菌与治疗策略呼吸科常见耐药革兰
12、阴性杆菌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，变形杆菌肠杆菌属，沙雷菌，枸橼酸菌，变形杆菌 铜绿假单胞菌铜绿假单胞菌，其他假单胞菌，其他假单胞菌 鲍曼不动杆菌鲍曼不动杆菌，其他不动杆菌，其他不动杆菌 嗜麦芽窄食单胞菌属嗜麦芽窄食单胞菌属 伯克霍尔德菌属伯克霍尔德菌属 产碱杆菌属，黄杆菌属产碱杆菌属，黄杆菌属NPRS结果显示，铜绿和鲍曼作为结果显示，铜绿和鲍曼作为MDR问题正在凸现问题正在凸现e5吸科耐药革兰阴性杆菌与治疗策略细菌耐药是否会影响病死率细菌耐药是否会影响病死率?治疗肺炎杆菌治疗肺炎杆菌ESBL菌株血液菌株血液感
13、染感染(n=31)合适治疗合适治疗(n=19)病死率病死率 5%不恰当治疗不恰当治疗(n=12)病死率病死率 42%P=0.02Source:Schiappa et al JID 1996;74:529-36e5吸科耐药革兰阴性杆菌与治疗策略e5吸科耐药革兰阴性杆菌与治疗策略在在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e5吸科耐药革兰阴性杆菌与治疗策略MDR引起肺炎的防治策略引起肺炎的防治策略 预防医院内肺炎（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早期、准确的病原学诊断，不要治疗定植菌和污染菌 停
14、止无效、耐药的抗生素，避免更严重的后果停止无效、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，甚至允许范围缩短用药间隔，甚至24h24h连续点滴连续点滴 旧药新用：多粘菌素旧药新用：多粘菌素E E，舒巴坦对不动杆菌等，舒巴坦对不动杆菌等 联合用药：联合用药：MICMIC为为16ug/ml16ug/ml的头孢他啶和的头孢他啶和16ug/ml16ug/ml的阿米的阿米卡星合用可能有效；特门汀与氨曲南联合治不发
15、酵糖卡星合用可能有效；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菌效果有时很好；氨曲南可耐受金属酶e5吸科耐药革兰阴性杆菌与治疗策略 Managing 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 D Division of Pulmonary and Critical Care Medicine,North Shore University Hospital,
16、Manhasset,NY 11030,USAe5吸科耐药革兰阴性杆菌与治疗策略VAP预防方法的有效性评价预防方法的有效性评价Route of intubationSearch for sinusitisCircuit changesHumidifierHumidifier changesEndotracheal suctioningSubglottic secretion drainageChest physiotherapyTracheostomyKinetic bedsSemi-recumbent positionProne positionStress ulcer prophylaxis
17、Prophylactic antibioticse5吸科耐药革兰阴性杆菌与治疗策略e5吸科耐药革兰阴性杆菌与治疗策略Antiseptic impregnated endotracheal tubes for the prevention of bacterial colonization 在实验室气道模型中建立不同对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包裹有洗必泰和碳酸银 抗菌抗菌ETT和对照和对照 ETT(未包裹）用浓度未包裹）用浓度108cfu/ml的菌液污染，的菌液污染，5天孵
18、育，管腔的远端和近端分别天孵育，管腔的远端和近端分别采样细菌培养采样细菌培养 抗菌抗菌ETT细菌定植量为细菌定植量为1-100 cfu/管，而对照管，而对照ETT达达106cfu/管管(P 24 hrs.INTERVENTIONS:Patients were randomized 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 discharg
19、e 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 significant differences between groups of patients in age,sex,diagnosis groups,mortality,number of aspirations per day,and APCHE II score.No significant differences
20、: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 by 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
21、 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):115-9e5吸科耐药革兰阴性杆菌与治疗策略Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia:a role for routine endotracheal aspirate cultures 方法：方法：299需要机械通气至少需
22、要机械通气至少48 h的病例，每的病例，每周两次采集气管内吸引物（周两次采集气管内吸引物（EA）定量培养。）定量培养。发生发生VAP后用后用 BAL培养确定病原体，并与培养确定病原体，并与EA结果进行比较。结果进行比较。最后有最后有75例诊断例诊断VAP，41例例BAL培养阳性，先培养阳性，先前常规前常规EA培养中有培养中有34例例(83%)阳性，阳性，1例早发例早发肺炎发生肺炎发生VAP时还没有采集时还没有采集EA；4例结果不一例结果不一致但抗菌药物选用合适，致但抗菌药物选用合适，2例选用药物有延迟例选用药物有延迟 结论：结论：每周两次常规每周两次常规EA培养培养对早期正确选用对早期正确选用
23、VAP治疗抗菌药物是合适的治疗抗菌药物是合适的Chest.2005 Feb;127(2):589-97e5吸科耐药革兰阴性杆菌与治疗策略Blind and bronchoscopic sampling methods in suspected VAP-A multicentre prospective study.OBJECTIVE:To compare 4 sampling methods:blind tracheal aspirate(blind TA),blind protected telescoping catheter(blind PTC),bronchoscopic PTC an
24、d 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 the four sampling methods.Direct examination an
25、d 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 VAP were diagnosed.Direct examination of PTC(eit
26、her 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 characteristics(ROC)curve was smaller for blind TA(0.
27、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 0.91,p=0.27,respectively).CONCLUSIONS:Blind P
28、TC 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):1319-26e5吸科耐药革兰阴性杆菌与治疗策略Combination therapy with polymyxin B for the treatment of multidrug-resistant Gram
29、-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.PATIENTS AND METHODS:We retrospectively reviewed the clinical
30、 and microbiological efficacy,and safety pro 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 administered in combination with another antimicrobial agent.RESULTS:Patients
31、 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 in three patients(10%)and did not result in discontinuation of the
32、rapy.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 Antimicrob Chemother.2004 Aug;54(2):566-9e5吸科耐药革兰阴性杆菌与治疗策略铜绿假单胞菌铜绿假单胞菌Pseu
33、domonas aeruginosae5吸科耐药革兰阴性杆菌与治疗策略A 7-year study of severe hospital-acquired pneumonia requiring ICU admission 在在1616张和张和2020张内科张内科-外科外科ICUICU中，连续观中，连续观察需要入住察需要入住ICUICU的重症的重症HAPHAP，共，共7 7年。年。9696次重症次重症HAPHAP中，中，GNBGNB占占5151，PAPA最常见最常见（2424）。）。5151例（例（5353）死亡，）死亡，曲菌和曲菌和PAPA引起的肺引起的肺炎病死率最高炎病死率最高。感染性休克
34、感染性休克(OR:14.27)(OR:14.27)和和COPD(OR:COPD(OR:6.11)6.11)是影响预后的独立危险因素。是影响预后的独立危险因素。Intensive Care Med.2003 Nov;29(11):1981-8e5吸科耐药革兰阴性杆菌与治疗策略鲍曼不动杆菌鲍曼不动杆菌Acinetobacter baumanniie5吸科耐药革兰阴性杆菌与治疗策略Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on m
35、orbidity 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 patients with multiple VAP episodes
36、(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 Acinetobacter spp,Stenotrophomonas maltophi
37、lia,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 similar among the groups.The mortality r
38、ate 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,1.44-12.71).Additionally,experiencing
39、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.These findings reinforce the importance
40、 of developing and refining a unit-specific pathway for the empiric management of VAP.J Trauma.2005 Jan;58(1):94-101e5吸科耐药革兰阴性杆菌与治疗策略鲍曼不动杆菌泛耐株的治疗鲍曼不动杆菌泛耐株的治疗Treatment of pan-drug resistant Acinetobacter baumannii 方法：方法：89例例PDRAB感染用不同方案治疗：感染用不同方案治疗：A组组(n=39)：carbapenem sulbactam；B组组(n=30)：2/3 代代cepha
41、losporins,antipseudomonas penicillins,or fluoroquinolones+aminoglycosides 结果：两组临床结果无差异：感染吸收结果：两组临床结果无差异：感染吸收(25/59,42%vs 12/30,40%)或存活或存活(35/59,59%vs 17/30,57%)。但。但48株株细菌中有细菌中有16株对株对imipenem/sulbactam敏感，单独对敏感，单独对imipenem敏感仅敏感仅2株；株；8株对株对meropenem/sulbactam敏敏感，单独对感，单独对meropenem敏感仅敏感仅3株株 结论：结论：carbapen
42、em-sulbactam合用不能明确是否可提合用不能明确是否可提高临床效果，但可降低高临床效果，但可降低 PDRAB菌株的菌株的MIC，早期用，早期用药可能对防治药可能对防治PDRAB有价值有价值Scand J Infect Dis.2005;37(3):195-9e5吸科耐药革兰阴性杆菌与治疗策略Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections 评价多粘菌素评
43、价多粘菌素E和利福平联合应用对和利福平联合应用对MDR铜绿铜绿假单胞菌的抗菌活性假单胞菌的抗菌活性 在在7株试验细菌中有株试验细菌中有6株有协同作用，使株有协同作用，使MIC下下降达到治疗水平。降达到治疗水平。在在4例难治的由例难治的由MDR铜绿引起的临床病例铜绿引起的临床病例(sepsis 或肺炎或肺炎)中均获得成功治疗中均获得成功治疗 结论：微生物和临床观察发现多粘菌素结论：微生物和临床观察发现多粘菌素E和利和利福平有协同作用，可用于难治性耐多药铜绿假福平有协同作用，可用于难治性耐多药铜绿假单胞菌的治疗单胞菌的治疗J Chemother.2004 Jun;16(3):282-7e5吸科耐药革兰阴性杆菌与治疗策略e5吸科耐药革兰阴性杆菌与治疗策略
