多重耐药菌感染的治疗.ppt

多重耐药菌感染的治疗,李光辉复旦大学华山医院抗生素研究所liguanghui,mdr定义,无公认的定义对现行之标准治疗产生耐药之细菌第三代头孢菌素耐药肠杆菌科细菌青霉素耐药肺炎链球菌碳青霉烯类耐药铜绿假单胞菌碳青霉烯类耐药不动杆菌vremrsa,visa,vrsa-,革兰阳性菌,prsp,青霉素0.190%jauregui,cidnov15,2005,clinicalefficacyofweeklydalbavancinvsstandard-of-careantimicrobialsforsssis,standard-of-careantibioticsincludedcefazolin,vancomycin,clindamycin,ceftriaxone,andpiperacillin/tazobactam.,seltzereetal.clininfectdis.2003;37:1298-1303.,dalbavancin(zeven),与万古霉素比较?治疗gpc所致导管相关性bsi临床有效率:dalbavancin=87%万古霉素=50%raadetal,cidfeb2005,telavancin,新一代糖肽类治疗csssi细菌清除率:telavancin=92%万古霉素=68%stryjewskietal,aacmar2006,telavancin,新一代糖肽类对gpc呈浓度依赖性快速杀菌作用mrsa,mrse,vre,visa,vrsa随即对照双盲iii期临床试验(n=167)telavancinqdvs耐酶青霉素qid或万古霉素bid,stryjewskimeetal.clininfectdis.2005;40:1601-1607.,oritavancin,新一代糖肽类作用机制同万古霉素对gpc呈浓度依赖性杀菌作用mrsa,mrse,vre消除半衰期132-356hrs临床试验qd给药，但qweek更好2项治疗csssis临床试验疗效良好,guaydr.pharmacotherapy.2004;24:58-68.,ceftobiprole,四代后头孢菌素对mrsa具有活性对gnb活性与3/4gcs相仿适应证：2008,3,19fda批准复杂性皮肤软组织感染,临床有效率,ceftarolinefosamil(ppi-0903,tak-599),新一代头孢菌素对mrsa，mdrsp和gnb均具抗菌活性ii期临床试验与万古霉素比较治疗csssi获满意疗效iii期临床试验中,sanfranciscocalif.september292006,46thicaac,克拉普林(iclaprim）,新二氢叶酸还原酶抑制剂广谱抗菌作用抗革兰阳性菌活性较强mrsa,visa/vrsa和大环内酯类、氟喹诺酮类和tmp耐药菌株肺炎链球菌，包括青霉素、红霉素、左氧氟沙星和smz-tmp耐药菌株对gnb和不典型病原体具有活性期临床试验与万古霉素比较获满意效果正在进行期临床试验,晚霉素(evernimicin),晚霉素(evernimicin,ziracin)抗mrsa与vre活性优于万古霉素与synercid静脉给药，t1/21.22h正在进行期临床试验,aurograb,aurograb为抗mrsa单抗和万古霉素结合药物主要用于治疗mrsa的感染正处于期临床试验阶段,arbekacin,aderivativeofdibekacin,isanaminoglycosidedevelopedandusedinjapanforthetreatmentmrsainfections,nationwideinvestigationinjapanontheefficacyofarbekacininmrsainfections,aclinicalinvestigationofmrsainfectionstostudytheefficacyofarbekacinwascarriedin115institutionsinjapan348patientswereevaluated.74patientsweretreatedwithabkaloneand274withabkincombinationwithothercompoundsbacteriologicalclinicalefficacywas75.6%/67.9%inpureinfectionand63.6%/71.3%inpolymicrobialinfectionadverseeffectswereseenin4.76%/5.7%,butnocasewasserious.abnormallaboratoryfindingswerenotedin15.4%ofcases,drugsexpclinres.1994;20(6):225-32.,肠球菌感染的治疗,首选青霉素或氨苄西林庆大霉素（全身感染）;磷霉素,呋喃妥因（仅用于uti）青霉素耐药或过敏糖肽类fq、氯霉素、rfp或多西环素（根据药敏）糖肽类耐药利奈唑胺600mgpo或ivq12hq-d7.5mg/kgivq8h,达托霉素，替加环素体外有效呋喃妥因或磷霉素对uti有效vanb菌株：替考拉宁联合ag。临床试验q-d有效率70，利奈唑胺相仿,万古霉素耐药肠球菌（vre）,最新趋势利奈唑胺耐药增多：匹兹堡13daptomycin耐药出现建议常规作利奈唑胺药敏，daptomycin应作e-test,革兰阴性菌,耐药菌感染的治疗,产esbl肠杆菌科细菌，耐3gcs或氨曲南重症感染：碳青霉烯类、fqag尿路感染：smz-tmp、am-cl、呋喃妥因、fq备注头孢吡肟、tc/cl、pip/taz体外具有活性，但动物实验效果差，部分高产esbls菌株对tc/cl、pip/taz原发耐药注意部分产esbls菌株体外可对2、3gcs敏感，但对头孢他啶耐药；此类菌株所致感染用2、3gcs治疗无效如对fq敏感，可能有效注意kpc菌株少数菌株仅对多粘菌素敏感,carbapenemase-producingklebsiellapneumoniae,organismsthatproducekpchavesimilarresistanceprofilestomostesbls,butwiththeadditionofcarbapenemresistance.treatmentoptionstigecyclinepolymyxinsothertetracyclines(attimes)aminoglycosides(attimes),pharmacotherapy.2008;28(2):235-249,铜绿假单胞菌,治疗选择抗假单胞菌青霉素类哌拉西林、哌拉西林/他唑巴坦、替卡西林/克拉维酸抗假单胞菌头孢菌素类头孢他啶、头孢哌酮、头孢哌酮/舒巴坦、头孢吡肟碳青霉烯类亚胺培南、美罗培南、帕尼培南氨基糖苷类庆大霉素、妥布霉素、阿米卡星、异帕米星氟喹诺酮类环丙沙星、左氧氟沙星除尿路感染外通常联合用药，内酰胺类（ag或fq）,耐药菌感染的治疗,铜绿假单胞菌:耐亚胺培南及美罗培南选用药物环丙沙星（根据药敏）氨基糖苷类（根据药敏）粘菌素静脉给药备注许多菌株仍对氨曲南和头孢他啶或appen敏感appen+ag、或头孢他啶+ag可能有效,鲍曼不动杆菌,治疗选择碳青霉烯类氨苄西林/舒巴坦、头孢哌酮/舒巴坦(舒巴坦对不动杆菌具高度活性),或氟喹诺酮类(环丙沙星,左氧氟沙星)联合氨基糖苷类以预防耐药并获协同作用体外具有活性米诺环素/多西环素替加环素多粘菌素,鲍曼不动杆菌感染的治疗,鲍曼不动杆菌:耐亚胺培南、appen或cef、ag、fq选用药物：含舒巴坦制剂（舒巴坦单用对部分鲍曼不动杆菌有效）黏菌素有效备注：6/8例鲍曼不动杆菌脑膜炎am/sb治疗痊愈，其中7例对亚胺培南耐药fq+ag、泰能+ag或rfp、或appen或apcef+ag对部分泛耐药株具有活性体外活性：黏菌素+泰能+rfp,替加环素,jac(2007)60,12061215,jac(2007)60,12061215,lancetinfectdis2006;6:589601,jantimicrobchemother.2008feb;61(2):417-20,jantimicrobchemother.2008jul;62(1):45-55,jantimicrobchemother.2008jun;61(6):,jantimicrobchemother.2008jun;61(6):,efficacyandsafetyofhigh-doseampicillin/sulbactamvs.colistinasmonotherapyforthetreatmentofmultidrugresistantacinetobacterbaumanniiventilator-associatedpneumonia,methodsaprospectivecohortstudyinadultcriticallyillpatientswithvapamp/sulb(9gevery8h)orcol(3miuevery8h)intravenouslyresultsatotalof28patientswereenrolled(15col,13amp/sulb).resolutionofsymptomsandsignsoccurredin60%(9/15)ofthecolgroupand61.5%(9/13)oftheamp/sulbgroup,improvementin13.3%(2/15)vs.15.3%(1/13)andfailurein26.6%(4/15)vs.23%(3/13bacteriologicsuccesswasachievedin66.6%(10/15)vs.61.5%(8/13)inthecolandamp/sulbgroupsmortalityrates(14daysand28days)were15.3%and30%fortheamp/sulband20%and33%forthecolgroupadverseeventswere39.6%(including33%nephrotoxicity)forthecolgroupand30.7%(15.3%nephrotoxicity)fortheamp/sulbgroup(p=ns)conclusioncolistinandhigh-doseam/sbwerecomparablysafeandeffectivetreatmentsforcriticallyillpatientswithmdra.baumanniivap,jinfect.2008jun;56(6):432-6,managementofmdrpathogens,ifpaeruginosa,combinationtherapyisrecommendedifacinetobacterspp,themostactiveagentsarethecarbapenems,sulbactam,colistin,andpolymyxinavoidmonotherapywithathird-generationcephalosporinforesbl+enterobacteriaceaeconsideradjunctiveinhaledaminoglycosideformdrgram-negativepneumoniainpatie