吸科耐药革兰阴性杆菌与治疗策略课件

1、呼吸科耐药革兰阴性杆菌与治疗策略 1呼吸科耐药革兰阴性杆菌与治疗策略 1CAP: 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-clavulanateComorb

2、idities (COPD, Diabetes, Renal 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

3、 RFQ2CAP: OutpatientPreviously HealCAP: 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 a

4、n issue: B-lactam plus either AM or RFQPseudomonas 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 o

5、r a macrolidePseudomonas infection 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 HomeReceiving treatment in nursing home: RFQ alone or amoxicillin-clavulanate

6、plus AMHospitalized: Same as for medical ward and ICU3CAP: InpatientMedical Ward3NNIS报告的医院内肺炎病原体检出率排位8082(15331)9096(13433)80829096枸橼酸菌111111肠杆菌91143大肠杆菌8456肺炎杆菌10834其他克雷伯41811奇异变形杆菌5268其他变形杆菌001413粘质沙雷菌4377其他沙雷菌101213肠杆菌科合计4230绿脓杆菌131722金葡菌131911CoNS12138肠球菌22108念珠菌3595其他26254NNIS报告的医院内肺炎病原体检出率排位80

7、82(153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):3442-75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Nosocomial tracheobronchitis in MV patients:incidence, aetiology and outcomeSurgical Medical Patients n 36 165 Gram-negative microorganisms 34 (77.2) 162 (78.7) Pseudomonas aerugin

8、osa 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)

9、Gram-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: 14831489.6Nosocomial tracheobronchitis i 医院内肺炎病原菌（Meta分析，全国19901998年，6062株菌） 病原体菌株构成绿脓杆菌124120.6克雷伯菌60810.1大肠杆菌3565.9肠杆菌属2784.6不动杆菌2754.6嗜麦芽窄食

10、单胞1001.7流感嗜血杆菌500.8金黄色葡萄球菌3585.9肠球菌831.4肺炎链球菌611.07 医院内肺炎病原菌（Meta分析，全国19901998年病原菌发生类型株数%早发性晚发性鲍曼不动杆菌1121318.6铜绿假单胞菌1101115.7金黄色葡萄球菌36912.9大肠埃希菌0557.1阴沟肠杆菌1457.1肺炎克雷伯菌1345.7粘质沙雷菌0445.7念珠菌1345.7嗜麦芽窄食单胞0334.3变形杆菌0334.3表皮葡萄球菌1122.9肠球菌1122.9产碱杆菌0222.9肺炎链球菌1011.4洛菲不动杆菌0111.4黄杆菌0111.4合计115970100.0 52例VAP病

11、原分布(9901) 8病原菌发生类型株数%早发性晚发性鲍曼不动杆菌1121318.NLRTI前五位病原菌在6个常见科室的比较 9NLRTI前五位病原菌在6个常见科室的比较 9医院内肺炎病原早期中期晚期1 3 5 10 15 20链球菌流感杆菌金葡菌 MRSA肠杆菌肺克，大肠绿脓杆菌不动杆菌嗜麦芽窄食单胞菌入院天数10医院内肺炎病原早期中期晚期1 3 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11呼

12、吸科常见耐药革兰阴性杆菌肺炎克雷伯杆菌，大肠埃希菌11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; 74:529-3612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1313在ICU中肺部感染耐药菌问题尤为突出14在ICU中肺部感染耐药菌问题尤为突出14MDR引起肺炎的防治策略预防医院内肺炎（HAP、VAP、HCAP）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

13、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24h连续点滴旧药新用：多粘菌素E，舒巴坦对不动杆菌等联合用药：MIC为16ug/ml的头孢他啶和16ug/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15MDR引起肺炎的防治策略预防医院内肺炎（HAP、VAP、HCManaging Infection In The Critical Care Unit: How Can Infection Control Make The ICU Safe?Crit Care Clin. 2005

14、 Jan;21(1):111-28 Shulman L, Ost DDivision of Pulmonary and Critical Care Medicine, North Shore University Hospital, Manhasset, NY 11030, USA16Managing Infection In The CritVAP预防方法的有效性评价Route of intubationSearch for sinusitisCircuit changesHumidifierHumidifier changesEndotracheal suctioningSubglotti

15、c secretion drainageChest physiotherapyTracheostomyKinetic bedsSemi-recumbent positionProne positionStress ulcer prophylaxisProphylactic antibiotics17VAP预防方法的有效性评价Route of intubati1818Antiseptic 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

16、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 randomized into two groups; one group was suctioned with CS and another group with the OS. MEASUREMENTS: Throat swabs were taken at ad

17、mission 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 significant differences between groups of patients in age, sex, diagnosis groups, mortality, number of aspirations per

18、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 by MV duration; in the incidence of exogenous VAP; in the microorganisms responsible for pneumonia. Patien

19、t 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):115-921Ventilator-associated pneumoniEarly antibiotic treatment for BAL-confirmed ventilator-ass

20、ociated 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):589-9722Ear

21、ly antibiotic treatment forBlind 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 and bronchoscopic BAL, for diagnosis

22、 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 and quantitative cult

23、ures 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 (either blind

24、 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 (0.78

25、, 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). CONCLUS

26、IONS: 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):1319-2623Blind and bronchoscopic sampliCombination therapy with polymyxin B for the treatme

27、nt 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. PATIENTS AND METHODS: We r

28、etrospectively 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 administered in combination with

29、 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 in three pati

30、ents (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 Antimicrob Chemot

31、her. 2004 Aug;54(2):566-924Combination therapy with polym铜绿假单胞菌Pseudomonas aeruginosa25铜绿假单胞菌25A 7-year study of severe hospital-acquired pneumonia requiring ICU admission在16张和20张内科-外科ICU中，连续观察需要入住ICU的重症HAP，共7年。96次重症HAP中，GNB占51，PA最常见（24）。51例（53）死亡，曲菌和PA引起的肺炎病死率最高。感染性休克(OR: 14.27)和COPD (OR: 6.11) 是影响

32、预后的独立危险因素。Intensive Care Med. 2003 Nov;29(11):1981-826A 7-year study of severe hospi鲍曼不动杆菌Acinetobacter baumannii27鲍曼不动杆菌27Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patientsBACKGRO

33、UND: 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 (200 VAP episodes; mean 2.4; range 2-5). An episode of IEAT

34、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 maltophilia, or Alcaligenes xylosoxidans. All the patients

35、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 rate was 3.6% for no episodes, 8.8

36、% 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 multiple IEAT episodes was associated with prolonged intensive care unit stay (p = 0.007) and prolonged mechanical ventilation (p = 0.005). CO