嚴(yán)重感染治療策略

1、邱海波東南大學(xué)醫(yī)學(xué)院附屬中大醫(yī)院東南大學(xué)急診與危重病醫(yī)學(xué)研究所,重癥感染的重要性 細(xì)菌耐藥機(jī)制及ICU細(xì)菌流行情況 重癥感染的治療策略－感染灶的充分引流－早期經(jīng)驗(yàn)性治療－正確的目標(biāo)性治療,,內(nèi) 容 提 要,醫(yī)院內(nèi)感染的發(fā)生率,普通病房中一般病人: 6-17%ICU病人：25-40%,Sepsis = Infection+SIRS,細(xì)

2、菌侵入,臨床體征,infection損傷 SIRS sepsis severe sepsis septic shock MODS/ MOF,感染過(guò)程,,,,,,,Impact of adequate empirical antibiotic therapy on the outcome of pats admitted to I

3、CU with sepsis,CCM, 2003, 31: 2742,Annual incidence of severe sepsis: 3 cases/ 1,000 Kill: 1,400 people worldwide /d 25 people /hMoreover, No. of sepsis pats is projected to increase by 1.5% per annum 嚴(yán)重感染的病死人數(shù)超過(guò)乳腺癌

4、、直腸癌、結(jié)腸癌、胰腺癌和前列腺癌的總和嚴(yán)重感染 vs AMI:發(fā)病率相同，病死率明顯高,Sepsis in worldwide,Surviving Sepsis Compaign拯救Sepsis運(yùn)動(dòng),,巴塞羅那宣言,ESICM SCCM ISF 2002年10月2日, 西班牙,全球Sepsis的發(fā)病率和死亡率均很高，耗費(fèi)大量的人力物力呼吁全球 醫(yī)務(wù)專(zhuān)業(yè)人員和組織、政府、衛(wèi)生機(jī)構(gòu)甚至公眾支持該行動(dòng)Improve su

5、rvival in severe sepsisAIM: 5年內(nèi)Sepsis死亡率減少25%,第一階段/Phase I,Develop guidelines Bedside clinician could use to improve outcome in severe sepsis ans septic shock,第二階段/Phase II,ESICM SCCM ISFAACCN/ACCP/ACEP/ATS/ANZICS/

6、ESCMID/ERS/SIF,Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555,Guidelines for management of severe sepsis/ septic shockInitial resuscitation: early goal-directed therapyDiagnosis: appropriate cultureAntib

7、iotic therapy: Early broad-spectrum, reassessed 2-3d Source control: Fluid therapy: colloids=crystalloids,VLTVasopressors: After VLS, NE vs Dopa, Low-dose dopa is not , cath for vaso Inotropic therapy: low CO-dobu,

8、high CO is notSteroid: low dose rhAPC: APACHE II >25, sepsis-induced ARDS/MOF and no bleeding risk,第二階段/Phase II,Guidelines for management of severe sepsis/septic shockBlood product administration: target Hb 7-9g

9、/dl, EPO only in renal failureMechanical ventilation: Ppla<30, Hypercapnia, optimal PEEP, Prone positionSedation, analgesia and NBMs: ProtocolGlucose control: <150mg%Renal replacement: Bicarbonate: pH < 7.

10、15DVT: UH/LMWHStress ulcer prophylaxis: H2blocker,第二階段/Phase II,To use the management guidelinesTo evalute the impact on clinical outcome of severe sepsis,第三階段/Phase III,ESICM SCCM ISFAACCN/ACCP/ACEP/ATS/ANZICS/ES

11、CMID/ERS/SIF,重癥感染的重要性 細(xì)菌耐藥機(jī)制及ICU細(xì)菌流行情況 重癥感染的治療策略 －感染灶的充分引流 －早期經(jīng)驗(yàn)性治療 －正確的目標(biāo)性治療,內(nèi) 容 提 要,MRS 耐苯唑西林，對(duì)Vaco敏感性降低VRSAPRP 耐青霉素和多重耐藥的肺炎鏈球菌VRE 耐萬(wàn)古霉素的腸球菌ESBL 產(chǎn)生超廣譜β-Lac酶的KPN和EcoAmpC 持續(xù)高

12、產(chǎn)AmpC酶的 陰溝、腸桿菌和弗 勞地枸櫞酸桿菌等Multi-res 多重耐藥銅綠、嗜麥芽和不動(dòng)桿菌,細(xì)菌耐藥--全球性難題,細(xì)菌的抗生素耐藥機(jī)制,改變細(xì)胞膜的通透性 使抗生素滲透障礙產(chǎn)生滅活酶和鈍化酶改變抗生素作用靶位,ESBLs Plasmid-Mediated Extended Spectrum Beta-Lactamase,對(duì)三代頭孢菌素如頭孢他啶、頭孢曲松、頭孢噻肟或氨曲南

13、的抑菌圈減小(R、I、S)加克拉維酸可使抑菌圈擴(kuò)大(≥5 mm)如為ESBL，應(yīng)報(bào)告所有青霉素類(lèi)，頭孢菌素類(lèi)，氨曲南耐藥，即使體外敏感，也應(yīng)視為耐藥,ESBLs與高產(chǎn)AmpC的差異,ESBLs 高產(chǎn)AmpC耐藥譜多重多重三代頭孢耐藥耐藥四代頭孢部分敏感敏感棒酸敏感不敏感哌酮/舒巴坦多敏感耐藥 PIP/三唑多敏感耐藥頭霉素敏感耐藥碳青霉烯類(lèi)敏

14、感敏感,,,,,,,32個(gè)醫(yī)院1994-2001年大腸桿菌及肺炎克雷伯菌產(chǎn)生ESBLs百分率,101 66,319 263,260 229,356 270,300 150,158 164,數(shù)字為株數(shù),%,年,ESBLs對(duì)重癥感染患者的預(yù)后有明顯影響,臨床研究證明：ESBL組死亡率(40%)明顯高于無(wú)ESBL組(18%）,（P=0.06),,抗生素應(yīng)用與AmpC突變,抗生素種類(lèi)治療后耐藥的發(fā)生率三代頭孢菌素

15、 19%(6/13)氨基糖苷類(lèi) 1%(1/89)亞胺配南 0%(0/17)其他 0%(0/33)最初敏感的菌株，經(jīng)治療后出現(xiàn)耐藥,Joseph W. Chow, et al. Ann Int Med, 1991, 115(8):585-590,三代頭孢不僅可誘導(dǎo)ESBLs，也可選擇出AmpC,三代頭孢選擇出高產(chǎn)AmpC耐藥菌的速度,使用的出現(xiàn)耐藥的MI

16、C(治療前)MIC(治療后)抗菌藥物抗菌藥物抗菌藥物mg/mlmg/ml使用天數(shù)頭孢唑肟頭孢唑肟8324頭孢他啶，慶大霉素頭孢他啶≤2>165頭孢噻肟，阿米卡星頭孢噻肟≤4>326頭孢噻肟，慶大霉素頭孢噻肟8327頭孢噻肟頭孢噻肟≤4>3216頭孢他啶，妥布霉素頭孢他啶≤2>1618,高產(chǎn)AmpC腸桿菌耐藥與三代頭孢使用的關(guān)系,三代

17、頭孢使用4-18天后就可選擇出高產(chǎn)AmpC霉腸桿菌耐藥菌,Joseph W. Chow, MD, et al. Annals of Internal Medicine. 1991; 115:585-590,AmpC酶流行情況,約30-50%腸桿菌屬 (弗勞地枸櫞酸菌,沙雷氏菌)高產(chǎn)AmpC酶131株三代頭孢耐藥的E coli的耐藥分析 ESBL’s 13.7% 高產(chǎn)AmpC34.0%

18、 其他酶機(jī)制6.5%,JAMA 2000,產(chǎn)AmpC酶耐藥菌引發(fā)的臨床后果更加嚴(yán)重,產(chǎn)AmpC霉腸桿菌屬感染患者死亡率是非耐藥菌感染患者的2倍,產(chǎn)AmpC酶細(xì)菌感染的患者死亡率更高,Joseph W. Chow, MD, et al. Annals of Internal Medicine. 1991; 115:585-590,持續(xù)高產(chǎn)AmpC酶的對(duì)策,中重度感染應(yīng)選擇的抗生素：碳青霉烯類(lèi)、四代頭孢、氟喹喏酮類(lèi)、氨基糖苷類(lèi)避

19、免使用第三代頭孢、酶抑制劑復(fù)合藥,AmpC 酶,Inoue K, et al. Chemotherapy 1995, 41(4): 257-266,SSBL--24株陰溝腸桿菌的耐藥情況,酶型株數(shù)三嗪 他啶吡肟 亞胺配南AmpC+14 14 14 0 0ESBL+4 4 2 4 0AmpC+ESBL+5 5 5 20From PUMC hosp

20、ital,,,,超級(jí)?內(nèi)酰胺酶耐藥(SSBL) Super Spectrum Beta Lactamases,ESBLs/高產(chǎn)AmpC酶位于同一細(xì)菌或細(xì)菌質(zhì)粒,,NPRS-7年最常見(jiàn)的G-菌（株數(shù)）,銅綠假單胞菌大腸埃希菌克雷伯菌屬不動(dòng)桿菌屬腸桿菌屬嗜麥芽窄單胞菌變形桿菌屬沙雷菌屬其它假單胞菌屬枸櫞酸桿菌屬,,時(shí)間：1994年～2001年醫(yī)院：4～14家菌株：554～1949株,,NPRS-7年最常見(jiàn)的革蘭陰性菌（

21、株數(shù)）,,菌株數(shù),554 1048 1348 1542 1291 1678 1949,總菌株,,1994～2001年主要抗菌素對(duì)革蘭陰性菌敏感率變化趨勢(shì),,敏感率％,,1994～2001年亞胺培南等主要抗菌素對(duì)革蘭陰性菌敏感率變化趨勢(shì),,敏感率％,ICU重癥感染的重要性 細(xì)菌耐藥機(jī)制及ICU細(xì)菌流行情況 重癥感染的治療策略 －感染灶的充分引流 －早期經(jīng)驗(yàn)性治療與降階梯策略 －

22、正確的目標(biāo)性治療,內(nèi) 容 提 要,Source control-Grade E,Every pats presenting with severe sepsis should be evaluated for the presence of a focus of infection amenable to source control measuresDrainage of an abscess or local focus of i

23、nfectionRemoval of a potientially infected device,Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555,重癥感染的重要性 細(xì)菌耐藥機(jī)制及ICU細(xì)菌流行情況 重癥感染的治療策略－感染灶的充分引流－早期經(jīng)驗(yàn)性治療與降階梯策略－正確的目標(biāo)性治療,內(nèi) 容 提 要,34,早期經(jīng)驗(yàn)性治療的對(duì)象,對(duì)有急性而危及生命的全身性

24、感染患者無(wú)法及時(shí)得到細(xì)菌學(xué)資料應(yīng)根據(jù)本病房的細(xì)菌流行病學(xué)調(diào)查結(jié)果選擇對(duì)常見(jiàn)致病菌有效的廣譜抗生素經(jīng)驗(yàn)性治療＝推理性治療,提高患者的生存率降低細(xì)菌產(chǎn)生耐藥性,早期經(jīng)驗(yàn)性治療的目標(biāo),Dr. Jordi RelloProfessor of Critical Care ,University Rovira & virgili Tarragona, Spain,,死亡： 絕對(duì)危險(xiǎn)度下降16%,死亡： 絕對(duì)危險(xiǎn)度下降8%,早期有

25、效抗感染治療的重要性,,死亡： 絕對(duì)危險(xiǎn)度下降6.1%,早期有效抗感染治療的重要性,死亡： 絕對(duì)危險(xiǎn)度下降9％,Impact of adequate empirical antibiotic therapy on the outcome of pats admitted to ICU with sepsis,CCM, 2003, 31: 2742,死亡： 絕對(duì)危險(xiǎn)度下降23%,不適當(dāng)?shù)慕?jīng)驗(yàn)性治療---概念,根據(jù)細(xì)菌培養(yǎng)結(jié)果起始治療的抗

26、生素未能針對(duì)引起感染的某一種或多種細(xì)菌或細(xì)菌對(duì)所用的抗生素耐藥認(rèn)為經(jīng)驗(yàn)性治療是不恰當(dāng)?shù)摹?（Kollef和 Ibrahim分別于 1999和 2000年的研究）,ICU嚴(yán)重感染病人起始抗生素治療覆蓋面不足--死亡率增加,ICU經(jīng)驗(yàn)性抗生素治療VAP:22-73%為抗生素起始治療不當(dāng),醫(yī)院獲得性肺炎--迅速恰當(dāng)?shù)目股刂委煟黠@提高生存率,Luna CM et al.Chest 1997,Adequate38%(6/1

27、6)Not-adequate/not-ANT81.6%(40/49),132 pats with suspected NPBAL in 55 pats,Bloodstream infections,Leibovici et alAdequate vs inadequate initial antibiotic: Mortality: 20% vs 34% From J Intern Med, 1998, 244:

28、379,Antibiotic therapy,1. Grade EIntravenous antibiotic therapy should be started within 1st h of recognition of severe sepsis, after appropriate cultures have been obtained,,Guidelines for sepsis. Intensive Care Med

29、2004, 30: 536-555,Antibiotic therapy,2. Grade DInitial empiric anti-infective therapy should include one or more drugs that have activity against the likely pathogensThe choice of drug should be guided by the suscepti

30、bility patterns of microorganisms in the community and the hospital,,Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555,Antibiotic therapy,降階梯治療策略的特性 (De-Escalation Therapy),是抗感染的經(jīng)驗(yàn)性治療方案，具有如下兩個(gè)特性： 開(kāi)始即使用廣譜抗生素

31、以覆蓋所有可能的致病菌 隨后(48-72h)根據(jù)微生物學(xué)檢查結(jié)果調(diào)整抗生素的使用，使之更有針對(duì)性,Dr. Luciano GattinoniProfessor of Anesthesiology,Institute of Emergency Surgery,University of Milan, Italy,如何保證起始治療的準(zhǔn)確性Getting it right (A--protocol),Treatment protocol

32、s and guidelines---important tool for optimal therapy Establishing local susceptibility profiles that can be used to develop therapy protocols“Not only we did want to treat with the initial therapy that was appropriate

33、, but we wanted to minimize the emergence of resistance”,CCM 2001， 29：1109－1115,如何保證起始治療的準(zhǔn)確性Getting it right (A),CCM 2001， 29：1109－1115,如何保證起始治療的準(zhǔn)確性Getting it right (B-Bacteria resis),It is essential to be able to reco

34、gnize those pats who are treatment failure,CCM 2003， 31：676,抗生素治療3d－VAP無(wú)效---tended to be survivors有效---tended to be non-SMore importantlyThose pats who had no clinical response within the first 3d were receiving in

35、adequate antimicrobial therapy,Most common pathogens associated with inadequate initial antimicrobial threapy,PA: Pseuso aeruginosa; SA:Staphylococcus aureus; AS: Acinetobacter species; KP: Klebsiella pneumoniae; ES: En

36、terobacter species; SP: Strep pneumoniaeOther: E coli, Haemophilus influ, Serratia,Kollef MH Clinical Inf Dis 2000, 31 (S4):131-8,,不動(dòng)桿菌的問(wèn)題,院內(nèi)肺炎常見(jiàn)病因環(huán)境中普遍存在對(duì)抗菌素耐藥嚴(yán)重耐受肥皂醫(yī)務(wù)工作者手上最常分離到的G—,,,抗菌素對(duì)不動(dòng)桿菌屬敏感性,敏感菌的比例%,,,銅綠假單胞菌的問(wèn)

37、題,院內(nèi)獲得性呼吸機(jī)相關(guān)性肺炎的首位病因引起的菌血癥死亡率70%所有廣譜抗菌素對(duì)其耐藥已升至20~37%,,,2001年抗菌素對(duì)銅綠假單胞菌活性,,中介加耐藥率％,機(jī)械通氣時(shí)間與既往抗生素治療是多重耐藥致病菌VAP的獨(dú)立危險(xiǎn)因素,Trouillet JL et al.Am J Respir Crit Care Med 157:531-39, 1998,銅綠假單胞菌建議治療方案－聯(lián)合用藥,亞胺培南與阿米卡星聯(lián)用，耐藥率降至7％亞

38、胺培南與環(huán)丙沙星聯(lián)用，耐藥率降至10％,『1994～2001年中國(guó)重癥監(jiān)護(hù)病房非發(fā)酵糖細(xì)菌的耐藥變遷』 中華醫(yī)學(xué)雜志 2003，83，5；385－340,,細(xì)菌交叉耐藥,一類(lèi)抗生素的應(yīng)用可導(dǎo)致細(xì)菌對(duì)另一類(lèi)抗生素的耐藥,銅綠假單胞菌,經(jīng)驗(yàn)性治療,,外排泵MexAB-OprM系統(tǒng)的表達(dá)增加,膜孔蛋白OprD表達(dá) 降低,喹諾酮類(lèi),對(duì)喹諾酮類(lèi)耐藥,對(duì)碳青霉烯類(lèi)的耐藥,對(duì)喹諾酮類(lèi)選擇性的nfxc(mexT)突變株,,大多數(shù) beta-內(nèi)酰胺類(lèi)

39、藥物 (包括美羅培南，但不包括IMP) 喹諾酮類(lèi), 四環(huán)素類(lèi), 氯霉素類(lèi), TMP,14th ECCMID,聯(lián)合用藥,16 beds MICU of 1300 beds teaching hospital1993.5~1995.6VAP occurring after >7 d of MV and prior antibiotic use,Trouillet JL. Am J Respir Crit Care Med 1

40、998, 157: 531~539,% susceptibility,,細(xì)菌耐藥特點(diǎn),VAP病原菌耐藥的危險(xiǎn)因素:最重要的是最近接受過(guò)抗生素治療(最近15天)其次是機(jī)械通氣至少7天,經(jīng)驗(yàn)性治療,VAP的致病菌,敏感性最高,IMP＋Amikacin＋Vanco,聯(lián)合用藥,Laforce: noncritically ill pts with NPSchleupner: noncritically ill pts with NP (S

41、 pneumo, H influ )Hilf: pats with bacteremia involving P aeruginosa,Prospective, multicenter6 ICU in Argentina63Pats, MV＞72hClinical evidence of VAP and bacteriologic confirmation by BAL or blood culturesCPIS measu

42、red at 3 d before VAP (VAP-3); at the onset of VAP (VAP); and at 3 (VAP+3), 5 (VAP+5), and 7 (VAP+7) days after onset,Luna CM.Crit Care Med 2003,31(3) 676-82,降階梯治療,如何保證起始治療的準(zhǔn)確性Getting it right (C-Clinical evaluation),簡(jiǎn)化

43、的臨床診斷標(biāo)準(zhǔn)Clinical Pulmonary Infection Score,Value PointsTemperature C > 36.5 and 38.5 and 39 or 4,000 and 11,000 1 Tracheal secretions Few0 Moderate1

44、 Large2 PaO2/FiO2, mmHg > 240 or present ARDS1 < 240 and absent ARDS 0 Pulmonary radiography no infiltrate 0

45、 Patchy or diffuse infiltrate 1 localized infiltrate 2,,Luna CM. CCM, 2003, 31: 676,Luna CM et al. Crit Care Med 2003, 31(3):676-82,P=0.013,P=0.005,治療反應(yīng)差,治療反應(yīng)好,病死率,持續(xù)評(píng)價(jià)CPIS可評(píng)估VAP患者的臨床轉(zhuǎn)歸,臨床表現(xiàn)在降階梯治療中的應(yīng)用

46、,如何保證起始治療的準(zhǔn)確性Getting it right (C-Clinical evaluation),Antibiotic therapy,3.2 Grade EExperts:Combination therapy for neutropenic patientsBroad-specturm therapy ueually must be continued for the duration of the neutro

47、penia,,Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555,Antibiotic therapy,Antibiotic therapy,4. Grade EIf the presenting clinical syndrome is determined to due to a non-infectious cause, antimicrobial thera

48、py should be stopped promptly to minimize the development of resistant pathogens and superinfection with other pathogenic organisms,,Guidelines for sepsis. Intensive Care Med 2004, 30: 536-555,Antibiotic therapy,,降階梯治療的

49、藥物選擇,對(duì)于ESBLs，頭孢菌素并不是經(jīng)驗(yàn)治療的好選擇 對(duì)于產(chǎn)AmpC酶的腸桿菌科細(xì)菌，頭孢菌素和酶抑制劑復(fù)合制劑的治療失敗率非常高,亞胺培南是降階梯治療的最佳選擇,Dr.David PatersonVisiting Associate Professor, Department of Medicine,University of Pittsburgh Medical Center Pittsburgh,Pennsylvania

50、,USA,StageⅠ,最能獲益的患者：以下原因?qū)е碌膰?yán)重感染 HAP VAP 菌血癥 膿毒癥（包括細(xì)菌和真菌） 嚴(yán)重的社區(qū)獲得性肺炎 腦膜炎等,經(jīng)驗(yàn)性治療,初始廣譜抗生素經(jīng)驗(yàn)治療降低病死率,ICU重癥感染的重要性 細(xì)菌耐藥機(jī)制及ICU細(xì)菌流行情況 重癥感染的治療策略 －感染灶的充分引流 －早期經(jīng)驗(yàn)性治療 －正確的目標(biāo)性治療,內(nèi) 容 提 要

51、,Antibiotic therapy,3. Grade EThe antimicrobial regimen should always be reassessed after 48~72h on the basis of using a narrow-antibiotic to prevent the development of resistance, to reduce toxicity, and costs,,Guideli

52、nes for sepsis. Intensive Care Med 2004, 30: 536-555,Antibiotic therapy,降階梯治療策略的特性 (De-Escalation Therapy),是抗感染的經(jīng)驗(yàn)性治療方案，具有如下兩個(gè)特性： 開(kāi)始即使用廣譜抗生素以覆蓋所有可能的致病菌 隨后(48-72h)根據(jù)微生物學(xué)檢查結(jié)果調(diào)整抗生素的使用，使之更有針對(duì)性,Stage II 降階梯以減少耐藥優(yōu)化治療成本效益比

53、,目標(biāo)性治療,經(jīng)驗(yàn)性治療盡早轉(zhuǎn)為目標(biāo)性治療轉(zhuǎn)換所需時(shí)間反映抗感染治療水平,如何實(shí)現(xiàn)降階梯 ？,明確病原體、敏感性，同時(shí)也應(yīng)意識(shí)到微生物學(xué)結(jié)果可能的局限性（時(shí)間性，in vitro） 根據(jù)藥敏結(jié)果評(píng)估初始抗生素，必要時(shí)做相應(yīng)調(diào)整 根據(jù)初始治療是否使患者有所好轉(zhuǎn) 根據(jù)患者體征和臨床反應(yīng)性，治療時(shí)間個(gè)體化,降階梯治療,病原學(xué)診斷－降階梯中的作用,初始經(jīng)驗(yàn)性治療之前，應(yīng)采集呼吸道標(biāo)本呼吸道標(biāo)本的病原學(xué)檢查結(jié)果并不總是可靠的,細(xì)菌耐藥

54、性試驗(yàn)(藥敏)及時(shí)、正確、反復(fù)標(biāo)本采樣 標(biāo)準(zhǔn)化的細(xì)菌培養(yǎng)和藥敏試驗(yàn)選擇敏感的抗生素監(jiān)測(cè)：細(xì)菌培養(yǎng)和藥敏,如何實(shí)現(xiàn)降階梯Getting it right (A-Bac culture),Luna CM et al. Crit Care Med 2003, 31(3):676-82,P=0.013,P=0.005,治療反應(yīng)差,治療反應(yīng)好,病死率,持續(xù)評(píng)價(jià)CPIS可評(píng)估VAP患者的臨床轉(zhuǎn)歸,臨床表現(xiàn)在降階梯治療中的應(yīng)用,如何實(shí)現(xiàn)降

55、階梯Getting it right (B--Clinical evaluation),73,目標(biāo)性治療－藥代動(dòng)力學(xué)與藥效學(xué),Pharmacokinetics,Pharmacodynamics,,,Drug concentration at site of infectionSerum levelTissue level,EffectGrowth inhibitionKillingClinical cureClini

56、cal failure,如何實(shí)現(xiàn)降階梯Getting it right (C-Decrease Res),殺菌速度不同,綠膿桿菌美羅培南雖然最終可以達(dá)到和亞安培南相同的殺菌速度,但在最初的5小時(shí)內(nèi),亞安培南殺菌速度明顯高于前者,Comparative in vitro killing activity of meropenem versus imipenem against multiresistant nosocomial Ps

57、eudomonas aeruginosa. J Chemother 1995 Jun;7(3):179-83,起始?xì)⒕钚?起始?xì)⒕钚?泰能>克倍寧>美平 泰能分子量?。?99），且電荷中性； 美平分子量（437.51） 泰能比美平更快速地進(jìn)入細(xì)菌[Evaluation of antibiotics by the method of initial bacte

58、ricidal activity] Matsuda K,Inoue M. Banyu Pahrnaceutical Co.,Ltd.,2-3 Nihonbashi-Honcho 2-Chome,Chuo-ku, Tokyo 103-8416,Japan,76,目標(biāo)性治療－ 組織滲透能力,血漿濃度組織濃度,,Prospective multicenter randomized study

59、Pats with microbiologically proven VAPReceive appropriate initial empiric treatment for 8 (n=197) vs 15 d (n=204)Mortality and recurrent infection: No diffAntibiotic-free days: 13.1d vs 8.7d (P<0.001)Multirsist

60、ance pathogens emerged significantly less frequently in 8d group than 15d group (42.1% vs 62.4%, P=0.04),減少抗生素療程－Safety,JAMA, 2003, 290: 2598,早期經(jīng)驗(yàn)性治療,嚴(yán)重感染抗菌藥物的原則,碳青霉烯類(lèi)/或加Van(Teico)或加抗真菌藥物,目標(biāo)性治療,,根據(jù)細(xì)菌學(xué)結(jié)果+臨床療效,選用一個(gè)廣譜抗