《最新重症患者真菌感染聚焦念珠菌及氟康唑的地位76广西北海M1PPT文档.ppt》由会员分享，可在线阅读，更多相关《最新重症患者真菌感染聚焦念珠菌及氟康唑的地位76广西北海M1PPT文档.ppt（82页珍藏版）》请在三一办公上搜索。
1、提 要,ICU与感染危重病人侵袭性真菌感染念珠菌来源抗真菌药物及选择关于氟康唑,提 要,ICU与感染危重病人侵袭性真菌感染念珠菌来源抗真菌药物及选择关于氟康唑,ICU 感染患者,感染性疾病诊治感染的预防与控制,重症感染入住ICUICU获得感染（ICU-acquired infections）,ICU内获得性感染的预防与控制,感染相关问题是ICU永恒主题ICU 工作要点之一是感染,75 countries1265 ICUS13 796 patients7087(51.4%)infected patients9084(71%)receiving antibioticsICU mortality r
2、ate 25%(infected)&11%(non-infected)(p.001)Infection accounted for 40%of total ICU expenditures,Site of infection 7087(51.4%of 13 796),Distribution of Nosocomial Infections by Site in Medical-Surgical ICU in US,Infect Control Hosp Epidemiol.2000;21:510-515.,Distribution of Nosocomial Infections by Si
3、te in Medical-Surgical ICU in US,Infections at three major sites represented 68%of all reported infections Nosocomial pneumonia 31%Urinary tract infections(UTIs)23%Bloodstream infections(BSIs)14%83%of episodes of nosocomial pneumonia were associated with mechanical ventilation(VAP)97%of UTIs occurre
4、d in catheterized patients(CAUTI)87%of primary BSIs in patients with a central line(CRBSI),ICU 与 感染,ICU感染病人：呼吸、腹腔、泌尿、血流ICU获得感染：呼吸、泌尿、血流、(手术部位-SICU),感染相关问题是ICU永恒主题ICU 工作要点之一是感染(51%感染病人）,提 要,ICU与感染危重病人侵袭性真菌感染真菌感染诊断相关问题抗真菌药物抗真菌药物选择,ICU感染的病原学,细菌(G+;G-;厌氧菌)不典型细菌真菌病毒etc,Mycoses.2012,55:435443,日本Toho 1955-
5、2006年间的10297例尸检进行分析,Mycoses.2012,55:435443,Among 2,984 ICU admissions,there were 489 deaths222 autopsies were conducted Post mortem examination revealed unexpected findings in 50 patients,Intensive Care Med.2004,30:20802085,Critical and urgent care:61-73,Positive isolates(4947/7087=70%),Vincent JL,e
6、t al.JAMA.2009,302(21):2323-2329.,Tortorano AM et al.Mycoses.2011,55:7379.,May 2006-April 200838 ICUs of 27 Italian hospitals 384 fungal infections(318 invasive Candida infections,63 mould infections and 3 cryptococcosis)were notified.,Aspergillus 57 Mucormycosis 4 Fusarium verticillioides 1Trichode
7、rma sp 1,CandidaAspergillusCryptococcosisMucormycosis,18 ICUs18-month study105 episodes IFIs occurred in 5,561 PatientsCandida:16.5 cases/1,000 admissions Filamentous fungi:2.3 cases/1,000 admissions,Filamentous fungi:mainly invasive pulmonary aspergillosis(IPA),Guo F,et al.J Antimicrob Chemother.20
8、13,68(7):1660-8.,中国16家大型教学医院HAP临床调查(599例分离到694株菌),Microbiology of Peritonitis,1.Laroche M,Harding G.Eur J Clin Microbiol Infect Dis.1998;17:542-550.2.Barie PS.J Chemother.1999;11:464-477.,B.fragilis groupClostridium spp.EnterococciS.EpidermidisMRSAPseudomonas+A.baumanniiCandida,B.fragilis groupClost
9、ridium spp.E.coliKlebsiella spp.Streptococcus Enterococcus spp.Candida,E.coliKlebsiella spp.Streptococcus spp.,Tertiary(Polymicrobial)2,Secondary(Polymicrobial)1,2,Primary(Monomicrobial)1,最初1-4周病原特征,Korean J Urol.2013;54:59-65,ESBL 53.1%,ESBL 37.5%,Wisplinghoff H,et al.Clinical Infectious Diseases.2
10、004;39:30917,1995-2002,Nosocomial bloodstream isolates(SCOPE Study),49 US hospitals7-year24,179 cases,Surveillance and Control of Pathogens of Epidemiological,Nosocomial Bloodstream Isolates(SCOPE Study),9.8%,23.2%,67.0%,Wisplinghoff H,et al.Clinical Infectious Diseases.2004;39:30917,Tortorano AM et
11、 al.Mycoses.2011,55,7379.,危重病人侵袭性真菌感染,Candida、Aspergillus、Cryptococcosis、MucormycosisICU:60%(-);40%(+);20%(Fungal,mostly candida)呼吸(Candida 5)腹腔(继发性、第三类型腹膜炎）泌尿(Candida 2-4)血流(Candida 3),其它部位,消化系统、骨关节、心血管系统等念珠菌最为常见,腹腔感染,以念珠菌最为常见（除外近平滑）,真菌血流感染,呼吸系统,泌尿系统,中枢神经系统,以隐球菌多见念珠菌，曲霉菌少见,常见病原体为曲霉菌和念珠菌、隐球菌（烟曲霉）,以念
12、珠菌最为常见(近平滑）,以念珠菌尿最为多见（除外近平滑）,侵袭性真菌感染,危重病人侵袭性真菌感染,提 要,ICU与感染危重病人侵袭性真菌感染念珠菌来源抗真菌药物及选择关于氟康唑,C.Albicans(白色念）C.Glabrata（光滑念）C.parapsilosis（近平滑念）C.Tropicalis（热带念）C.Krusei（克柔念）C.Guilliermondii（季也蒙念）C.Lusitaniae（葡萄牙念）,C.inconspicuaC.norvegensisC.dubliniensisC.lipolyticaC.zeylanoidesC.pelliculosaCandida spp.
13、,C.kefyrC.rugosaC.famata,Candida SPP.(165 species),C.Albican 白念Non C.Albicans 非白念,Candida Colonization,Pulmonary tree,Bowel,Vagina,Esophageal/GI,Candida:Infection sites,C.parapsilosis,C.tropicalis,C.albicans,C.krusei,C.glabrata,The Source of Candidemia,Clinical Infectious Diseases.2001,33:1959-67,Mo
14、del for Invasive CandidiasisBlijlevens,Donnelly,De Pauw.Brit J Haematol 2002;117:259-64,injury,antibiotics,GI tract,Lancet Infect Dis.2003.3:685-702,Nat Rev Microbiol.2013.10(2):112-122,Nat Rev Microbiol.2013.10(2):112-122,念珠菌来源,外源性：导管位置、导管护理内源性：胃肠粘膜保护、肠内营养定植&高负荷定植&感染,提 要,ICU与感染危重病人侵袭性真菌感染念珠菌来源抗真菌药物
15、及选择关于氟康唑,系统性抗真菌药：全球,isavuconazole,ravuconazole,fluconazole,itraconazole,posaconazole,L-AMB,ABCD,ABLC,voriconazole,caspofungin,micafungin,anidulafungin,Amphotericin B,Azoles,Candins,AMB,Phospholipid bilayerof the fungal cellmembrane,Fungalcell wall,b-(1,3)-glucan,b-(1,6)-glucan,b-(1,3)-glucan synthas
16、eGlucan Synthesis InhibitorEchinocadinCaspofunginMicafungin(FK463)Anidulafungin(LY303,306),ErgosterolPolyenes(AmB,LFAB)Azoles Fluconazole,ItraconazoleVoriconazolePosaconazoleRavuconazole(BMS-207,147),Antifungal Mechanisms of Action:“Newer”Antifungal Agents,nucleus,Nucleoside Analogs Flucytosine,Mayo
17、 Clin Proc.2011;86(8):805-817,General patterns of susceptibility of Candida Spp.,IDSA Guidelines.CID 2009,48:50335,CHIF-NET 2010,Journal of clinical microbiology.2010,48(4):13661377,In vitro susceptibilities of Candida spp.to uconazole and voriconazole,Journal of clinical microbiology.2010,48(4):136
18、61377,IDSA：Candidiasis Guideline 2009,Intensive Care Med.2009,35:206214,Carmeli like score,Antifungal systemic therapy according to Carmeli-like score,Carmeli-like score extended antifungal therapy algorithm,抗真菌药物及选择,抗真菌药物选择,唑类、多烯类、棘白菌素类机制抗真菌谱,严重程度粒细胞三唑类暴露局部的流行病学Carmeli Score,提 要,ICU与感染危重病人侵袭性真菌感染念珠
19、菌来源抗真菌药物及选择关于氟康唑,The Dosage of Fluconazole,AAC.1998,42(5):1105-1109,T MICCmax/MICAUC/MIC,抗真菌药物按PK/PD分类,Int J Antimicrob Agents.2012 Jan;39(1):1-10.,Fluconazole dose&Cmax and AUC,Fungal densities in kidneys of mice treated with various Fluconazole,Pharmacodynamic variables for five total doses of Flu
20、conazole,ED16,ED37,ED49,ED60,ED75,Dose-response curve,p=0.009,AAC.2007,51(10):3599-3604,Correlation of MIC data with Fluconazole treatment success,Correlation of Dose/MIC and AUC/MICversus outcomes,氟康唑剂量/MIC50时临床有效率可达86%以上,氟康唑不同给药剂量/MIC比值治疗粘膜/侵袭性念珠菌病总体临床治愈率,Pfaller MA.Clinical Microbiology Reviews.2
21、006;19(2):435-47.,三项侵入性念珠菌病的研究及一项粘膜感染的研究的汇总结果,PK/PD of Fluconazole,Dose Dependent AgentAUC/MIC 45-90Dose/MIC 50-100,S 8mg/l 6mg/kg/dSDD 16-32mg/l 12mg/kg/dR 64mg/l 20mg/kg/d,AndesD.Pharmacokinetics and Pharmacodynamics of Antifungals.Infect Dis Clin North Am.2006,20:679-697,IDSA Guidelines.CID 2009,
22、48:50335,Fluconazole at a dose of 10 mg/kg/day would seem to be an effective and safe drug for the management of C.albicans fungaemia,Graninger W et al.J Infect.1993;26:133-146,Current Medical Research and Opinion.2007,23(5):1057-1065,氟康唑首剂负荷剂量AUC更高,真菌症学術集会抄録集：27，2003(L20030303006),AUC/MIC,关于氟康唑,剂量依赖AUIC;Dose/MIC 50-100剂量 与 结局Loading dose,小 结,ICU与感染危重病人侵袭性真菌感染念珠菌来源抗真菌药物及选择关于氟康唑,
