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1、2020/9/18,Dr.HU Bijie,1,呼吸科耐药革兰阴性杆菌与治疗策略,株洲市二医院 刘和平副主任医师,2020/9/18,Dr.HU Bijie,2,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

2、 AM plus high-dose amoxicillin-clavulanate Comorbidities (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 I

3、nfluenza with bacterial superinfection: B-lactam or a RFQ,2020/9/18,Dr.HU Bijie,3,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) Inte

4、nsive Care Unit (ICU) Pseudomonas infection is not an issue: B-lactam plus either 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 a

5、ntipseudomonal agent plus an aminoglycoside plus RFQ or a macrolide Pseudomonas 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 Home Receiving treatmen

6、t in nursing home: RFQ alone or amoxicillin-clavulanate plus AM Hospitalized: Same as for medical ward and ICU,2020/9/18,Dr.HU Bijie,4,NNIS报告的医院内肺炎,2020/9/18,Dr.HU Bijie,5,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):3442-7,2020/9/18,Dr.HU Bijie,6,Nosocomial tracheo

7、bronchitis in MV patients:incidence, aetiology and outcome,Eur Respir J 2002; 20: 14831489.,2020/9/18,Dr.HU Bijie,7,医院内肺炎病原菌(Meta分析,全国19901998年,6062株菌),2020/9/18,Dr.HU Bijie,8,52例VAP病原分布(9901),2020/9/18,Dr.HU Bijie,9,NLRTI前五位病原菌在6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;26:880-885,2020/

8、9/18,Dr.HU Bijie,10,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,2020/9/18,Dr.HU Bijie,11,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,2020/9/18,Dr.HU Bijie,12,细菌耐药是否会影响病死率 ?,治

9、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=0.02,Source:Schiappa et al JID 1996; 74:529-36,2020/9/18,Dr.HU Bijie,13,2020/9/18,Dr.HU Bijie,14,在ICU中肺部感染耐药菌问题尤为突出,2020/9/18,Dr.HU Bijie,15,MDR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 加大剂量:从药敏单中寻找中介(低

10、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,2020/9/18,Dr.HU Bijie,16,Managing Infection In The Critical Care Unit: How Can Infection Control Make The ICU Safe? Crit Care Clin. 2005 Jan;21(1):111-28 S

11、hulman L, Ost D Division of Pulmonary and Critical Care Medicine, North Shore University Hospital, Manhasset, NY 11030, USA,2020/9/18,Dr.HU Bijie,17,VAP预防方法的有效性评价,Route of intubation Search for sinusitis Circuit changes Humidifier Humidifier changes Endotracheal suctioning Subglottic secretion drain

12、age Chest physiotherapy Tracheostomy Kinetic beds Semi-recumbent position Prone position Stress ulcer prophylaxis Prophylactic antibiotics,2020/9/18,Dr.HU Bijie,18,2020/9/18,Dr.HU Bijie,19,Antiseptic 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,

13、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 0.001). 结论:抗菌导管可有效预防VAP相关细菌在ETT上的生长,J Hosp Infect. 2004 Jun;57(2):170-4,2020/9/18,Dr.HU Bijie,20,Efficacy of heat and moisture exchangers in preventing VAP: meta-a

14、nalysis of RCT,OBJECTIVE: Several RCT have examined the effect of antibacterial humidification strategies, particularly the replacement of heated humidifiers (HH) by heat and moisture exchangers (HME), in preventing VAP. The present meta-analysis reviews these RCTs. METHODS: RCTs were identified by

15、searching the Medline and Cochrane Central Register of Controlled Trials databases from 1990 to 2003. We included RCTs using HMEs in the treatment group and HHs in the control group and reporting the incidence of pneumonia as a study outcome. Two investigators independently abstracted key data on de

16、sign, population, intervention and outcome of the studies. RESULTS: Between 1990 and 2003 eight RCTs met the inclusion criteria of this analysis. Pooling the results from these studies revealed a reduction in the relative risk of VAP in the HME group (0.7), particularly in MV with a duration of at l

17、east 7 days (five RCTs, relative risk 0.57). CONCLUSIONS: This meta-analysis found a significant reduction in the incidence of VAP in pts humidified with HMEs during MV, particularly in pts ventilated for 7 days or longer. This finding is limited by the exclusion of pts at high risk for airway occlu

18、sion from some of the studies. Contraindications (tenacious secretions, airway obstructive disease, hypothermia) and technical issues of HMEs must be considered. Further RCTs are necessary to examine the wider applicability of HMEs and their extended use.,Intensive Care Med. 2005 Jan;31(1):5-11,2020

19、/9/18,Dr.HU Bijie,21,Ventilator-associated pneumonia using a closed versus an open tracheal suction system,OBJECTIVE: The aim of this study was to analyze the prevalence of VAP using a closed-tracheal suction system (CS) vs. an open system (OS). SETTING: A 24-bed medical-surgical ICU in a 650-bed te

20、rtiary hospital. PATIENTS: Patients requiring MV for 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 discharge to classify pneumonia in endogenous

21、 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: in percentage of pts wh

22、o 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 US dollars +

23、/- 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):115-9,2020/9/18,Dr.HU Bijie,22,Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures,方法:299需要机械通气

24、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):589-97,2020/9/18,Dr.HU Bijie,23,Blind and bronchoscopic sampling methods in suspected VAP

25、- 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 of VAP. DESIGN 30(7):1319-26,2020/9/18,Dr.HU Bijie,24,Combination therapy with pol

26、ymyxin B for the treatment of multidrug-resistant Gram-negative respiratory tract infections,BACKGROUND: 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

27、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 adminis

28、tered 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 w

29、as observed 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 op

30、tions.,J Antimicrob Chemother. 2004 Aug;54(2):566-9,2020/9/18,Dr.HU Bijie,25,铜绿假单胞菌 Pseudomonas aeruginosa,2020/9/18,Dr.HU Bijie,26,A 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

31、率最高。 感染性休克(OR: 14.27)和COPD (OR: 6.11) 是影响预后的独立危险因素。,Intensive Care Med. 2003 Nov;29(11):1981-8,2020/9/18,Dr.HU Bijie,27,鲍曼不动杆菌 Acinetobacter baumannii,2020/9/18,Dr.HU Bijie,28,Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and

32、mortality among critically ill trauma patients,BACKGROUND: 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 V

33、AP 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 malto

34、philia, 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 gr

35、oups. 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, 1.44-12.71). Additionally, experiencing multiple IEAT episodes was associated with prolonged intensive care unit stay (p = 0.007) and prolonged mechanical ventilation (p = 0.005). CONCLUS

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