吸科耐藥革蘭陰性桿菌與治療策略

1、2024/2/28,Dr.HU Bijie,1,呼吸科耐藥革蘭陰性桿菌與治療策略,株洲市二醫(yī)院劉和平副主任醫(yī)師,2024/2/28,Dr.HU Bijie,2,CAP: Outpatient,Previously HealthyNo recent antibiotic therapy: A macrolidea or doxycyclineRecent antibiotic therapy: A respiratory fluo

2、roquinolone (RFQ) alone, an advanced macrolide (AM) plus high-dose amoxicillin or AM plus high-dose amoxicillin-clavulanateComorbidities (COPD, Diabetes, Renal or Congestive Heart Failure, or Malignancy)No recent ant

3、ibiotic 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 RF

4、Q,2024/2/28,Dr.HU Bijie,3,CAP: Inpatient,Medical 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

5、antibiotic therapy)Intensive Care Unit (ICU)Pseudomonas infection is not an issue: B-lactam plus either AM or RFQPseudomonas infection is not an issue but patient has B-lactam allergy: RFQ, with or without clindamycin

6、Pseudomonas 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 but patient ha

7、s 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 amo

8、xicillin-clavulanate plus AMHospitalized: Same as for medical ward and ICU,2024/2/28,Dr.HU Bijie,4,NNIS報告的醫(yī)院內(nèi)肺炎,2024/2/28,Dr.HU Bijie,5,銅綠假單胞菌、肺炎克雷伯菌和鮑曼不動桿菌是HAP常見的革蘭陰性桿菌,Antimicrob Agents Chemother. 2003 Nov;47(11):344

9、2-7,,2024/2/28,Dr.HU Bijie,6,Nosocomial tracheobronchitis in MV patients:incidence, aetiology and outcome,Eur Respir J 2002; 20: 1483–1489.,2024/2/28,Dr.HU Bijie,7,醫(yī)院內(nèi)肺炎病原菌（Meta分析，全國1990～1998年，6062株菌）,2024/2/28,Dr.HU B

10、ijie,8,52例VAP病原分布(99~01),2024/2/28,Dr.HU Bijie,9,NLRTI前五位病原菌在6個常見科室的比較,謝紅梅，胡必杰，何禮賢，等. 2819例醫(yī)院下呼吸道感染病原和預(yù)后分析.上海醫(yī)學(xué)2003；26：880-885,2024/2/28,Dr.HU Bijie,10,,,醫(yī)院內(nèi)肺炎病原,早期,中期,晚期,1 3 5 10

11、 15 20,鏈球菌,流感桿菌,金葡菌 MRSA,腸桿菌,肺克，大腸,綠膿桿菌,不動桿菌,嗜麥芽窄食單胞菌,入院天數(shù),2024/2/28,Dr.HU Bijie,11,呼吸科常見耐藥革蘭陰性桿菌,肺炎克雷伯桿菌，大腸埃希菌腸桿菌屬，沙雷菌，枸櫞酸菌，變形桿菌銅綠假單胞菌，其他假單胞菌鮑曼不動桿菌，其他不動桿菌嗜麥芽窄食單胞菌屬伯克霍爾德菌屬產(chǎn)堿桿菌屬，黃桿菌屬

12、NPRS結(jié)果顯示，銅綠和鮑曼作為MDR問題正在凸現(xiàn),2024/2/28,Dr.HU Bijie,12,細菌耐藥是否會影響病死率 ?,治療肺炎桿菌ESBL菌株血液感染 (n=31),合適治療 (n=19) 病死率 5%不恰當治療(n=12)病死率 42% P=0.02,Source:Schiappa et al JID 1996; 74:529-36,2024/2/28,Dr.HU Bijie,13,,,2024/2/28,Dr

13、.HU Bijie,14,,,在ICU中肺部感染耐藥菌問題尤為突出,2024/2/28,Dr.HU Bijie,15,MDR引起肺炎的防治策略,預(yù)防醫(yī)院內(nèi)肺炎（HAP、VAP、HCAP）早期、準確的病原學(xué)診斷，不要治療定植菌和污染菌停止無效、耐藥的抗生素，避免更嚴重的后果加大劑量：從藥敏單中尋找中介（低敏）的藥物聯(lián)合使用，在安全范圍內(nèi)的最大劑量，時間依賴性的藥在允許范圍縮短用藥間隔，甚至24h連續(xù)點滴舊藥新用：多粘菌素E，舒巴坦

14、對不動桿菌等聯(lián)合用藥：MIC為16ug/ml的頭孢他啶和16ug/ml的阿米卡星合用可能有效；特門汀與氨曲南聯(lián)合治不發(fā)酵糖菌效果有時很好；氨曲南可耐受金屬酶,2024/2/28,Dr.HU Bijie,16,Managing Infection In The Critical Care Unit: How Can Infection Control Make The ICU Safe?Crit Care Clin. 2005 Jan

15、;21(1):111-28 Shulman L, Ost DDivision of Pulmonary and Critical Care Medicine, North Shore University Hospital, Manhasset, NY 11030, USA,2024/2/28,Dr.HU Bijie,17,VAP預(yù)防方法的有效性評價,Route of intubationSearch for sinusitis

16、Circuit changesHumidifierHumidifier changesEndotracheal suctioningSubglottic secretion drainageChest physiotherapyTracheostomyKinetic bedsSemi-recumbent positionProne positionStress ulcer prophylaxisProphylact

17、ic antibiotics,2024/2/28,Dr.HU Bijie,18,,2024/2/28,Dr.HU Bijie,19,Antiseptic impregnated endotracheal tubes for the prevention of bacterial colonization,在實驗室氣道模型中建立不同對MRSA, PA, AB 和產(chǎn)氣腸桿菌有抗菌作用的氣管插管(ETTs) ，包裹有洗必泰和碳酸銀抗菌ETT

18、和對照 ETT (未包裹）用濃度108cfu/ml的菌液污染，5天孵育，管腔的遠端和近端分別采樣細菌培養(yǎng)抗菌ETT細菌定植量為1-100 cfu/管，而對照ETT達106cfu/管(P < 0.001).結(jié)論：抗菌導(dǎo)管可有效預(yù)防VAP相關(guān)細菌在ETT上的生長,J Hosp Infect. 2004 Jun;57(2):170-4,2024/2/28,Dr.HU Bijie,20,Efficacy of heat and moi

19、sture exchangers in preventing VAP: meta-analysis of RCT,OBJECTIVE: Several RCT have examined the effect of antibacterial humidification strategies, particularly the replacement of heated humidifiers (HH) by heat and moi

20、sture exchangers (HME), in preventing VAP. The present meta-analysis reviews these RCTs.METHODS: RCTs were identified by searching the Medline and Cochrane Central Register of Controlled Trials databases from 1990 to 20

21、03. 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 design, population,

22、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 t

23、he HME group (0.7), particularly in MV with a duration of at least 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

24、 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 occlusion from some of the studies. Contraindications (tenacious secretions, airway

25、 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):5-11,20

26、24/2/28,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 (C

27、S) vs. an open system (OS). SETTING: A 24-bed medical-surgical ICU in a 650-bed tertiary hospital. PATIENTS: Patients requiring MV for >24 hrs. INTERVENTIONS: Patients were randomized into two groups; one group was

28、 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

29、(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 diffe

30、rences: 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 microorganism

31、s 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). 結(jié)論:閉合痰液吸引系統(tǒng)不能降低VAP發(fā)病率，包括外源性肺炎,Crit

32、 Care Med. 2005 Jan;33(1):115-9,2024/2/28,Dr.HU Bijie,22,Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures,方法：299需要機械通氣至少48 h的病例，每周兩次采集氣管內(nèi)吸引物（

33、EA）定量培養(yǎng)。發(fā)生VAP后用 BAL培養(yǎng)確定病原體，并與EA結(jié)果進行比較。 最后有75例診斷VAP，41例BAL培養(yǎng)陽性，先前常規(guī)EA培養(yǎng)中有34例 (83%)陽性，1例早發(fā)肺炎發(fā)生VAP時還沒有采集EA；4例結(jié)果不一致但抗菌藥物選用合適，2例選用藥物有延遲結(jié)論：每周兩次常規(guī)EA培養(yǎng)對早期正確選用VAP治療抗菌藥物是合適的,Chest. 2005 Feb;127(2):589-97,2024/2/28,Dr.HU Bijie,23

34、,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),

35、 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

36、 h) and suspected nosocomial pneumonia. INTERVENTIONS: All patients underwent the four sampling methods. Direct examination and quantitative cultures of the four specimens were performed. MEASUREMENTS AND RESULTS: Visi

37、ble 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 (eithe

38、r 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 a

39、rea under receiver operating characteristics (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 ca

40、theter 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 PTC appears to be a good alternative to

41、bronchoscopic sampling for VAP diagnosis, provided that the sample contains visible secretions expelled from the catheter.,Intensive Care Med. 2004 Jul;30(7):1319-26,2024/2/28,Dr.HU Bijie,24,Combination therapy with poly

42、myxin 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 challeng

43、e. The use of polymyxin B has been resurrected specifically for this purpose. PATIENTS AND METHODS: We retrospectively reviewed the clinical and microbiological efficacy, and safety profile of polymyxin B in the treatme

44、nt 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. RESU

45、LTS: 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

46、48%. Nephrotoxicity was 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 treatm

47、ent option for MDR Gram-negative respiratory tract infections in the setting of limited therapeutic options.,J Antimicrob Chemother. 2004 Aug;54(2):566-9,2024/2/28,Dr.HU Bijie,25,銅綠假單胞菌Pseudomonas aeruginosa,2024/2/28,D

48、r.HU Bijie,26,A 7-year study of severe hospital-acquired pneumonia requiring ICU admission,在16張和20張內(nèi)科-外科ICU中，連續(xù)觀察需要入住ICU的重癥HAP，共7年。96次重癥HAP中，GNB占51％，PA最常見（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: 6.1

49、1) 是影響預(yù)后的獨立危險因素。,Intensive Care Med. 2003 Nov;29(11):1981-8,2024/2/28,Dr.HU Bijie,27,鮑曼不動桿菌Acinetobacter baumannii,2024/2/28,Dr.HU Bijie,28,Effect from multiple episodes of inadequate empiric antibiotic therapy for vent

50、ilator-associated pneumonia on morbidity and mortality among critically ill trauma patients,BACKGROUND: The purpose of this retrospective study was to determine the effect of inadequate empiric antibiotic therapy (IEAT)

51、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 was a VAP episode with empiric therapy h

52、aving 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 Alc

53、aligenes 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).

54、RESULTS: Demographics and injury severity were similar 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 logis

55、tic 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 assoc

56、iated 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 morbi

57、dity and mortality. These findings reinforce the importance of developing and refining a unit-specific pathway for the empiric management of VAP.,J Trauma. 2005 Jan;58(1):94-101,2024/2/28,Dr.HU Bijie,29,鮑曼不動桿菌泛耐株的治療Trea

58、tment of pan-drug resistant Acinetobacter baumannii,方法：89例PDRAB感染用不同方案治療：A組(n=39)：carbapenem ＋ sulbactam；B組(n=30)：2/3 代cephalosporins, antipseudomonas penicillins, or fluoroquinolones + aminoglycosides 結(jié)果：兩組臨床結(jié)果無差異：感染吸收

59、(25/59, 42% vs 12/30,40%)或存活(35/59, 59% vs 17/30, 57%)。但48株細菌中有16株對imipenem/sulbactam敏感，單獨對imipenem敏感僅2株；8株對meropenem/sulbactam敏感，單獨對meropenem敏感僅3株結(jié)論：carbapenem-sulbactam合用不能明確是否可提高臨床效果，但可降低 PDRAB菌株的MIC，早期用藥可能對防治PDRAB有價

60、值,Scand J Infect Dis. 2005;37(3):195-9,2024/2/28,Dr.HU Bijie,30,Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections,評價多粘菌素E和利福平聯(lián)合