替考拉宁临床应用PPT课件.ppt

对糖肽类抗生素临床应用的再认识,1,2,Folliculitis,Abscess,Cellulitis,StaphylococcusaureusSkinorSoft-TissueInfections,Necrotizingpneumonia,Endocarditis,Osteomyelitis,StaphylococcusaureusDeep-SeatedInfections,Intracranialinfection,3,当前用于耐药革兰阳性菌的抗生素,药名属类MRSPRPVISAVRE毒付作用及其他万古霉素糖肽YYXX肾毒替考拉宁糖肽YY溶血葡萄球菌弱夫西地酸YY利奈唑胺恶唑烷酮YYYY可贫血，血小板Quinupristin/链阳霉素YYYX粪肠球菌差Dalfopristin副作用达托霉素环酯肽YY呼吸道感染差替加环素四环素YYYY?oritavancin糖肽ly33328YYYY组织浓度不理想TelithromycinKetolideYYYY对MRSA弱,4,真的王牌经得起时间的考验,抗G+球菌：万古霉素替考拉宁抗G-杆菌：多粘菌素抗真菌：两性霉素B,5,替考拉宁对葡萄球菌属的抗菌活性,*替考拉宁对金葡菌的抗菌活性比万古霉素强24倍*替考拉宁对凝固酶阴性葡萄球菌的抗菌活性与万古霉素相似,但对溶血葡萄球菌的抗菌作用较万古霉素差,SpencerRC,GoeringR,IntJAntimicrobAgents1995;5:169-177,6,替考拉宁对链球菌属的抗菌活性,*替考拉宁对肺炎链球菌和化脓性链球菌等的抗菌活性较万古霉素稍强或相仿,SpencerRC,GoeringR,IntJAntimicrobAgents1995;5:169-177,7,替考拉宁对肠球菌属的抗菌活性,SpencerRC,GoeringR,IntJAntimicrobAgents1995;5:169-177,8,替考拉宁的抗菌活性,耐万古霉素肠球菌的耐药类型,9,替考拉宁对厌氧菌的抗菌活性,Glupczynskietal.EurJClinMicrobiol1984;3:50-51,10,11,MRSA菌血症、自体瓣膜感染性心内膜炎糖肽类首选,MRSA菌血症：非复杂性（迅速转阴，迅速退热，无心内膜炎、迁涉灶、假体）：万古霉素或达托霉素2周复杂性：万古霉素或达托霉素46周心内膜炎：万古霉素或达托霉素6周评估、处理菌血症的来源！菌血症者常规行心超检查！,12,万古霉素+利福平：6周万古霉素+庆大霉素：2周,MRSA人工瓣膜感染性心内膜炎推荐糖肽类,13,MRSA儿童菌血症、感染性心内膜炎首选糖肽类,万古霉素：15mg/kgq6h，26周鉴于替代药物疗效和安全性有限数据的考虑，不推荐利奈唑胺、克林霉素；达托霉素等选择也需慎重,14,2011IDSA糖肽类治疗MRSA菌血症与感染性心内膜炎推荐剂量,LiuC,etal.ClinicalPracticeGuidelinesbytheInfectiousDiseasesSocietyofAmericafortheTreatmentofMethicillin-ResistantStaphylococcusAureusInfectionsinAdultsandChildren.CID2011:52.,15,MRSA肺炎的推荐抗菌治疗,重症CAP（进入ICU/坏死或空洞浸润/脓胸）经验性治疗MRSA感染HA-MRSACA-MRSA伴脓胸MRSA肺炎，抗生素+引流儿童MRSA肺炎：万古霉素（克林霉素，替代利奈唑胺）,万古霉素利奈唑胺克林霉素,721天,LiuC,etal.ClinicalPracticeGuidelinesbytheInfectiousDiseasesSocietyofAmericafortheTreatmentofMethicillin-ResistantStaphylococcusAureusInfectionsinAdultsandChildren.CID2011:52.,16,2011IDSA糖肽类治疗MRSA肺炎推荐剂量,LiuC,etal.ClinicalPracticeGuidelinesbytheInfectiousDiseasesSocietyofAmericafortheTreatmentofMethicillin-ResistantStaphylococcusAureusInfectionsinAdultsandChildren.CID2011:52.,17,MRSA骨关节感染,骨髓炎：清创引流+万古霉素或达托霉素、利奈唑胺、克林霉素（+利福平），8周化脓性关节炎：同骨髓炎，34周骨关节、脊柱植入物术后感染：早发：同骨髓炎（+2周利福平）迟发：取出植入物儿童：万古霉素（克林霉素，达托霉素，利奈唑胺）,18,MRSA中枢神经系统感染,脑膜炎：万古霉素2周（+利福平）替代治疗：利奈唑胺，TMP-SMX引流管：取出，培养转阴后再置入脑脓肿、硬膜下积脓：切开引流+万古霉素46周（+利福平）替代治疗：利奈唑胺，TMP-SMX海绵窦栓塞：万古霉素46周（+利福平）替代治疗：利奈唑胺，TMP-SMX儿童：万古霉素,19,万古霉素治疗失败怎么办？,20,21,ImpactofIncreasingVancomycinDosage,Recommendedvancomycintroughlevel1015mg/Lor1520mg/LAchievableby15mg/kgever12hourBaddourLM,etal.Circulation2005;111:e394434GemmellCG,etal.JAntimicrobAgent2006;57:589608WangJT,etal.JAntimicrobAgent2001;47:246Highertroughlevel?2025mg/L:nooutcomedifferenceMorerenaltoxicityWysockiM,etal.AntimicrobAgentsChemother2001;45:24607,22,万古霉素治疗失败怎么办？,清创引流替代一：达托霉素+（庆大霉素，利福平，利奈唑胺，SMZco）替代二：奎奴普丁/达福普丁，SMZco，利奈唑胺，特拉万星,23,台湾传染病协会推荐替考拉宁为MRSA-HAP的经验性治疗,GuidelinesonantimicrobialtherapyofpneumoniainadultsinTaiwan,revised2006.JMicrobiolImmunolInfect.2007;40(3):279-283.,推荐替考拉宁作为MRSA感染的迟发性HAP和VAP的经验性治疗用药对于存在多重耐药危险因素和任何严重疾病的迟发性HAP(肺炎发生于入院第5天或以后)，推荐替考拉宁联合其他抗生素作为MRSA感染的经验性治疗用药对于VAP，推荐替考拉宁联合其他抗生素作为MRSA感染的经验性治疗用药,台湾成人肺炎抗生素治疗指南(2007)台湾传染病协会(IDST),24,亚洲HAP工作组专家共识推荐替考拉宁为MRSA-HAP的一线用药,SongJH,etal.AmJInfectControl.2008;36(4):S83-S92.,亚洲HAP工作组专家共识(2008),推荐万古霉素和替考拉宁作为治疗MRSA感染HAP的一线用药万古霉素具有肾毒性和耳毒性等副作用，治疗时需要严密监测其血药浓度；替考拉宁严重不良反应少，无需监测血药浓度为避免耐药菌株选择抗生素，利奈唑胺应作为治疗MRSA感染HAP的二线用药,25,英国MRSA感染预防和治疗指南推荐MRSA感染选用糖肽类治疗,GouldFK,etal.JournalofAntimicrobialChemotherapy.2009;63:849861.,英国MRSA感染预防和治疗指南(2008),无并发症的菌血症推荐使用糖肽类抗生素，疗程至少14d证据级别,严重皮肤软组织感染和/或菌血症高危因素的住院患者，可考虑使用使用糖肽类抗生素证据级别A,26,糖肽类分子结构,万古霉素,替考拉宁,27,组织浓度(%ofserumconcentration),28,1986-2007年265篇论文，RCT46篇，符合荟萃分析标准24篇。粒细胞减少伴发热和非粒细胞减少伴发热各12篇，病例数1872例结论：替考拉宁疗效与万古霉素相似（万古霉素MIC1.5），而不良反应（肾毒性）少于万古霉素,SyetitskyS,etal.Comparativeefficacyandsafetyofvancomycinversusteicoplanin:systematicreviewandmeta-analysis.AntimicrobAgentsChemother.2009;53:4069-79.,替考拉宁与万古霉素的疗效与安全性:荟萃分析,29,VancomycinTeicoplanin,-64%,p0.05,Hahn-AstCetal.Infection2008;36:548.,替考拉宁肾毒性发生率低于万古霉素,30,Nephrotoxicityofglycopeptides,Definations:50%riseincreatinine,JChemother2000;12(supp5):21-5,31,29/49,32/42,Hahn-AstCetal.Infection2008;36:548.,2/11,11/19,%,Overall,Overall,Pneumonia,Pneumonia,替考拉宁vs万古霉素-肺部感染,OverallvsPneumoniaClinicalEfficacyinFebrileNeutropenia,32,C.Tascini.et.al.JournalofChemotherapy.2009;21:311-316.,利奈唑胺与替考拉宁治疗G+菌感染的回顾性研究,33,菌血症及肺炎是两组患者最常见的感染类型,C.Tascini.etal.JournalofChemotherapy.2009;21:311-316.,34,临床有效率(%),32/37,12/15,15/22,7/10,15/16,11/14,13/16,9/14,13/14,8/13,利奈唑胺治疗各部位感染的临床有效率与替考拉宁无统计学差异,C.Tascini.etal.JournalofChemotherapy.2009;21:311-316.,研究结果,35,Time,MIC90,LogConcentration,24h-AUC,Troughlevel:15-20mg/L24h-AUC:800gh/mL(teicolanin)24h-AUIC(AUC24/MIC):AtleastanAUC24/MIC125，BetteranAUC24/MIC345or400,GlycopeptidesTime-dependentBacterialKilling,MIC,Dose,Dose,Cmax,TMIC,36,TeicoplaninPharmacokinetics,TeicoplanincanbegivenbytheIVorIMrouteLongserumhalflife(88182hrs)90%boundtoserumalbuminExcretedthroughthekidneys,80%ofthedosebeingrecoveredinurineand3%instoolin16days,37,4.98,7.64,9.4,一,一,TeicoplaninLevelsinCriticallyIllPatients202Patients,JAntimicrobChemother2003;51:9715.,Anappropriateloadingdoseofteicoplanin(6mg/kgevery12hforatleastthreedoses)wasadministeredonlyin38.6%ofcases41.2%withnormalrenalfunction8.7%withmoderatelyimpairedrenalfunction2.2%ofpatientswithtotallyimpairedrenalfunctionHypoalbuminaemicin74.5%Morerapiddistributionandhigherclearance,38,JAntimicrobChemother2003;51:9715.,4.24,6.47,10.8,6.11,11.22,8.66,TeicoplaninLevelsinCriticallyIllPatientsLoadingDoseIsNeeded,6mg/kgevery12hforthreedoses,39,4.98,7.64,9.4,一,一,TeicoplaninLevelsinCriticallyIllPatients202Patients,JAntimicrobChemother2003;51:9715.,40,NiwaTetal.IntJAntimicrobAgents2010;35:507-10.,KanazawaNetal.JInfectChemother2011;17:297-300.,MatsumotoKetal.JInfectChemother2010;16:193-9.,AhnBJ,etal.YonseiMedJ2011;52:616-23.,41,ClinicalResponsevs.TroughTeicoplaninLevelsCtrough13mg/Lon4thDay(N=69),MatsumotoKetal.JInfectChemother2010;16:193-9.,83%,20%,42,TeicoplaninDosingforMRSAInfections,Teicoplaninatotaldoseof36mg/kgduringthefirst3daysandatroughconcentrationof13mg/Lonthefourthday,9%,88%,36mg/kgwasrecommendedtoachieveCtrough13mg/L,MatsumotoKetal.JInfectChemother2010;16:193-9.,13,43,SerumLevelofTeicoplanin,12mg/kgq12hx3doses,followedby12mg/kg24hx1dose,6mg/kgq12hx3doses,followedby6mg/kg24hx1dose,Maintenancedose:both6mg/kg.day,WangJT,etal.Manuscriptprepared,44,RecommendedTeicoplaninLoadingDoses,Aloadingdoseof400mgq12hforthreedosesfollowedby400mgoncedaily:Noneachievedtheoptimalteicoplanintroughconcentrationwithin3days800mgand400mg12hapartonDay1and600mgand400mg12hapartonDay2,followedbyahighmaintenancedoseof400mg95%ofpatients(21/22)showedtheoptimalconcentration800mgonDay1followedby400mgonDays2and3isrecommendedastheinitialloadingdosestoach