陈佰义抗生素专项治理chen.ppt

陈佰义/辽宁省感染性疾病医疗中心/,“抗菌药物专项治理”中医务人员与管理者的角色-关注抗菌药物合理应用与临床管理,抗感染药物发展简史,1929AlexanderFleming发现青霉素,HowardFlorey和ErnstChain分离获得青霉素，用于动物试验。,青霉素首次用于救治战伤患者，拯救了许多人的生命,1950s大量抗生素用于临床。,AposterfromWorldWarII,dramaticallyshowingthevirtuesofthenewmiracledrug,andrepresentingthehighlevelofmotivationinthecountrytoaidthehealthofthesoldiersatwar.,DiscoveryofAntibacterialAgents,CycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycin,Imipenem,1930,1940,1950,1960,1970,1980,1990,2000,PenicillinProntosil,CephalosporinC,EthambutolFusidicacidMupirocinNalidixicacid,OxazolidinonesCecropin,Fluoroquinolones,Neweraminoglycosides,Semi-syntheticpenicillins119;405-411,ControlofAntibioticResistance,寻找新的抗感染药物-新药越来越少限制人以外(畜牧业)使用-减少对人类的影响优化抗感染药物预防VS治疗优化抗感染药物的临床管理加强医院感染的控制-减少耐药菌传播,细菌耐药的临床对策-MeasurestoResistance,-减少抗生素选择性压力,临床医生的职责,临床医生的职责,慢性咳嗽和黄痰-原因,哮喘后鼻腔鼻漏病毒感染后气道高反应性胃酸返流吸烟相关的慢性支气管炎支气管扩张症弥漫性泛细支气管炎肺泡蛋白沉积症,急性发热WBC不高/淋巴增高（无感染灶）病毒！WBC增高/中性粒增高/核左移可能细菌！部位/病原体？原发性菌血症？慢性发热IE、布病、慢性感染灶？结核病？非感染性发热药物热、风湿病、恶性肿瘤,正确诊断是正确治疗的前提,发热的诊断与鉴别诊断,CryptogenicOrganizingPneumonia,FightingInfectionInTheFirsthours,RapidtestsWhenavailable.Gramstain!,Startadequateantibioticcoverage(within1hour?)TillouAetal.AmSurg2004;70:841-4,Drainpurulentcollection,SamplingIncludinginvasiveprocedureswhenneeded(BAL),经验性治疗和目标治疗的统一留取标本进行微生物学检查开始经验性抗感染治疗目标治疗,选择哪种抗菌药物(whichantibiotic?)感染部位的常见病原学(possiblepathogensonsiteofinfection)选择能够覆盖病原体的抗感染药物(antibioticsrequirement)-抗菌谱/组织穿透性/耐药性/安全性/费用考虑药代动力学/药效动力学(PK/PD)考虑病人生理和病理生理状态(physiologicandpathophysiology)高龄/儿童/孕妇/哺乳(advancedage/children/pregnantwomen/breastfeeding)肾功能不全/肝功能不全/肝肾功能联合不全(renal/hepticdysfunction/combined)其它因素(otherconsiderations)杀菌和抑菌/单药和联合/静脉和口服/疗程(cidalvsstatic/monovscombination/IVvsPO/duration),经验性抗感染治疗药物选择-considerationsinchoosingantibioticforempirictherapy,培养结果前依据基本信息选择抗感染药物choosingAbxbeforecultureresult感染部位和可能病原体的关系associationofpathogenwithsiteofinfectionGram染色结果-与上述病原体是否符合？Gramstain-inaccordancewithsuspectedpathogen?某些病原体易于造成某些部位的感染Somepathogeneasilycausesomesiteofinfection,经验性抗感染治疗药物选择-considerationsinchoosingantibioticforempirictherapy,不同感染部位的常见感染性病原体Possiblepathogensonsiteofinfection,注意特殊修正因子/特别是先期抗菌药物对细菌学的影响,不同感染部位的常见感染性病原体Possiblepathogensonsiteofinfection,关注特殊病原体,肺孢子菌肺炎-免疫缺陷-相对特异临床-积极病原学检查,重症军团菌肺炎-发热、少痰-多肺叶、多肺段受累-肺外表现,抗菌谱(coverage)组织穿透性(tissuepenetration)耐药性(resistance,specificallylocalresistance)参考代表性资料/依靠当地资料安全性(safetyprofile)药物本身/制剂/工艺/杂质费用/效益(cost/effectiveness)失败或副作用致再治疗费用更高,经验性抗感染治疗药物选择的基本原则,评价病原体耐药可能？,是否耐药菌？-了解耐药病原体流行状况参考代表性治疗/依靠当地资料-个体化用药病人来源：社区、养老院、医院高龄、基础疾病、近期抗菌药物、近期住院、侵袭性操作、晚发医院感染,S.aureus,Penicillin,1944,Penicillin-resistantS.aureus,金黄色葡萄球菌耐药的发生发展过程,Methicillin,1962,Methicillin-resistantS.aureus(MRSA),Vancomycin-resistantenterococci(VRE),Vancomycin,1990s,1997,VancomycinintermediateS.aureus(VISA),2002,Vancomycin-resistantS.aureus,CDC,MMWR2002;51(26):565-567,1960,评价病原体耐药可能？,是否耐药菌？-了解耐药病原体流行状况参考代表性治疗/依靠当地资料-个体化用药病人来源：社区、养老院、医院高龄、基础疾病、近期抗菌药物、近期住院、侵袭性操作、晚发医院感染,中国大陆ESBL的发生率,%,WangH,ChenM.DiagnosMicrobiolInfectDis,2005,51,201-208CMSS/SEANIR/CARES.,year,细菌耐药监测结果如何解读？,实验室药物敏感性监测的意义及缺陷,意义-反映了耐药趋势/告诫我们要慎重使用抗菌药物-在制定用药方案时考虑耐药性导致的治疗失败缺陷-实验室收集到的菌株/大型教学医院/ICU抗生素选择压力导致耐药性高估！-没有临床背景资料/不利用于个体化用药(年龄、基础疾病、社区/医院感染、前期抗菌药物使用),PrevalenceofrectalcarriageofExtended-Spectrum-lactamase-producingEscherichiaColiamongelderlypeopleinacommunitysettinginShenyang,Crosssectionalstudy-276elderly、rectalswab/Ecoliisolation/ESBLscreening、genotypingandPEGFResult:prevalenceofESBLpositiveEColi7.0%（19/270）CTX-Mtype-CTX-M-1463.2%,other:CTX-M-22andCTX-M-24，2CTX-M-57-like-GAsubstitutionin865pointleadingtoDNsubsitutionin289pointinAA(new,sequenceNo.EF426798),TianSF,ChenBY.PrevalenceofrectalcarriageofExtended-Spectrum-lactamase-producingEscherichiaColiamongelderlypeopleinacommunitysettinginShenyang,China.CanadianJournalofmicrobiology2008;54:15,RiskfactorsforinfectionwithESBLproducers(MDR)outsidehospital,ColodneretalEJCMID200423,163.,医院感染-产ESBL细菌感染的危险因素,Prospectivestudyof455episodesofK.pneumoniaebacteremia(253nosocomial)in12hospitals30.8%为医院获得,ICU中43.5%产ESBLsESBLs危险因素-先期使用氧亚氨基-内酰胺类抗菌药物-过去14天内使用2d(OR=3.9).其它危险因素TPN,肾功衰竭,烧伤非ESBL危险:碳青霉烯、头孢吡肟、喹诺酮、氨基糖苷类Patersonetal:AnnInternMed2004;140:26-32.,VAP耐药菌感染的危险因素,135次VAPICU变量ORPMV7days6.0.009先期ABs13.57days/priorABs,Trouillet,etal.AmJRespirCritCareMed.1998;157:531,aExceptnonfermenters/non-Pseudomonasspecies.AdaptedfromCarmeliY.Predictivefactorsformultidrug-resistantorganisms.In:RoleofErtapenemintheEraofAntimicrobialResistancenewsletter.Availableat:www.invanz.co.il/secure/downloads/IVZ_Carmeli_NL_2006_W-226364-NL.pdf.Accessed7April2008;DimopoulosG,FalagasME.EurInfectDis.2007;4951;Ben-AmiR,etal.ClinInfectDis.2006;42(7):925934;Pop-VicasAE,DAgataEMC.ClinInfectDis.2005;40(12):17921798;ShahPM.ClinMicrobiolInfect.2008;14(suppl1):175180.,StratificationforRiskforMDRGram-NegativePathogens,EpidemiologyofMRSA,H-MRSAReservoires-hospitals-LTCFs5geneticbackgrouds,H-MRSAincommunity-patientswithriskfactors-contactwithpatientswithriskfactors,Truecommunity-MRSA-nohealthcare-associatedriskfactors-withPVLgenes,healthcare,community,AcquiredOnset,H-MRSA感染危险因素:年龄65岁，严重基础疾病，伤口广谱抗生素使用，住院时间延长，多次住院侵袭性操作（气管插管、切开/植入血管导管）,合理使用抗MRSA药物糖肽类/利奈唑胺,Greaterthan65yearsoldResidenceinalong-termcarefacilitySevereunderlyingdisease(Chronicliver,lung,orvasculardiseaseNeutropenia)Previous/multiplehospitalization/increasedLOS/StayinanICUPriororprolongedexposuretoantibioticsPresenceofinvasiveindwellingdeviceNeonatePresenceandsizeofawounddialysisExposuretocolonizedorinfectedpatient,RiskfactorsforMDRbugs,InfectControlHospEpidemiol2000;21:718-23,MRSAcolonizationorinfection,重症感染耐药菌感染！重症感染革兰阴性肠杆菌科细菌感染！-PCP、军团菌、肺炎链球菌都可致重症感染,是否重症?-依据临床表现/器官功能状态-氧和、血液动力学、肾功能、肠功能,PCP,LD,为什么随意使用超广谱药物或联合使用抗感染药物对于选择抗菌药物-耐药性VS严重性哪个更重要？,PCP,LD,耐药菌感染VS严重感染-PCP和LD告诉我们什么？,如何合理应用“高级”抗菌药物？,观点:耐药性判断对于合理选择抗菌药物更重要！包括重症感染,碳青霉烯抗MRSA药物抗真菌药物-要有指征使用！,选择哪种抗菌药物(whichantibiotic?)感染部位的常见病原学(possiblepathogensonsiteofinfection)选择能够覆盖病原体的抗感染药物(antibioticsrequirement)-抗菌谱/组织穿透性/耐药性/安全性/费用考虑药代动力学/药效动力学(PK/PD)考虑病人生理和病理生理状态(physiologicandpathophysiology)高龄/儿童/孕妇/哺乳(advancedage/children/pregnantwomen/breastfeeding)肾功能不全/肝功能不全/肝肾功能联合不全(renal/hepticdysfunction/combined)其它因素(otherconsiderations)杀菌和抑菌/单药和联合/静脉和口服/疗程(cidalvsstatic/monovscombination/IVvsPO/duration),经验性抗感染治疗合理选择药物-considerationsinchoosingantibioticforempirictherapy,评估病原体有的而放矢！评估耐药性到位不越位！,评估严重性广谱VS窄谱？单药VS联合？,选择哪种抗菌药物(whichantibiotic?)感染部位的常见病原学(possiblepathogensonsiteofinfection)选择能够覆盖病原体的抗感染药物(antibioticsrequirement)-抗菌谱/组织穿透性/耐药性/安全性/费用考虑药代动力学/药效动力学(PK/PD)考虑病人生理和病理生理状态(physiologicandpathophysiology)高龄/儿童/孕妇/哺乳(advancedage/children/pregnantwomen/breastfeeding)肾功能不全/肝功能不全/肝肾功能联合不全(renal/hepticdysfunction/combined)其它因素(otherconsiderations)杀菌和抑菌/单药和联合/静脉和口服/疗程(cidalvsstatic/monovscombination/IVvsPO/duration),经验性抗感染治疗药物选择-considerationsinchoosingantibioticforempirictherapy,选择抗菌药物时应考虑的其它因素OtherconsiderationsinchoosingAbx,杀菌vs抑菌(Cidalvsstatic)严重/复杂感染选杀菌剂cidalforseriousandcompicatedinfections单药vs联合(monotherapyvscombination)：静脉vs口服(IVvsoral)疗程(duration),联合用药的理由,补充单一用药的抗菌谱不足！协同作用如铜绿假单孢菌菌血症减少耐药？,2007ATS/IDSAGuidelines:Inpatients,MandellLA,etal.ClinInfectDis2007,CAPInpatientTherapy,MedicalWard,IntensiveCareUnit,RecentAntibiotic,NoRecentAntibiotic,RespiratoryFQaloneORAdvancedmacrolide+-lactam,NoPseudomonasRisk,No-lactamAllergy,-lactamAllergy,-lactam+advancedmacrolideOR+respiratoryFQ,*RegimendependonnatureofrecentAbxtherapy,RespiratoryFQ+aztreonam,PseudomonasRisk,No-lactamAllergy,-lactamAllergy,Anti-pseudomonal,antipneumococcalb-lactam/penem+Cipro/Levo750ORAnti-pseudomonal,antipneumococcalb-lactam/penem+aminoglycoside+Azithromycin,Aztreonam+respiratoryFQ+aminoglycoside,Advancedmacrolide+-lactamORrespiratoryFQ*,抗菌药物联合药敏,药物联合能够提高铜绿假单胞菌对药物的敏感率(平均增加3.49.2),CID2005，40(Suppl2)：S89一S98,TheDurationofAntimicrobialTherapy,Bacteriaload,Clinicalcourse,Recurrence,急性感染Acuteinfection,慢性感染，疗程不足Chronicinfection,durationnotenough,慢性感染，足疗程Chronicinfection,durationenough,抗感染药物的临床应用,治疗性应用经验治疗因无法确定感染的微生物，推断可能的病原体，参考本地区药敏监测结果，抗生素须覆盖所有可能微生物，常选用联合治疗或单一广谱抗生素,治疗性应用目标治疗确定病原体，选用窄谱、低毒性的抗生素,预防性应用,抗菌药物预防性应用的基本原则内科和儿科预防用药,抗菌药物临床应用指导原则,有明确应用预防指征者仅限于少数情况原则只能预防一或二种特定病原体只能一段时间内，不能长期使用不用于原发疾病不能治愈或缓解者不用于病毒、昏迷、休克、中毒、心衰、肿瘤不用于病毒性疾病:普通感冒、麻疹、水痘等不用于应用肾上腺皮质激素,预防对象抗菌药物风湿热复发青霉素或红霉素（青霉素过敏者）流行性脑脊髓膜炎SD、环丙沙星（成人）或头孢曲松结核病（与排菌者密切接触儿童）异烟肼疟疾（进入疫区者）青篙素、氯喹新生儿眼炎四环素、红霉素或硝酸银实验中不慎直接接触布鲁菌菌、鼠疫杆菌等四环素链霉素菌尿症（孕妇、婴幼儿、老人等）SMZCo、喹诺酮、阿莫西林,抗菌药物预防性应用的基本原则内科和儿科预防用药,PreventionofSSIs,PerioperativeantimicrobialprophylaxisHyperoxygenationMaintainnormalbodytemperatureHairremovalimmediatelypriortooperationusingelectricclippersHandwashingGoodsurgicaltechniqueMaintainnormalbloodsugarlevelsHostfactors,Normothermia,Clippingv.Shaving,GlucoseControl,and,Oxygenation,ProphylacticAntibiotics,外科围术期抗生素预防性应用,用不用?-预防用药的指证用什么?-选择抗菌药物的原则何时用?-用药时机怎么用?-用药途径用几次?-用药次数,感染的高危病人(HighRiskPatient)手术时间延长/病人术前ASA身体状态评分2分高危手术病人(HighRiskProcedure)II类清洁-污染切口及部分类污染切口上、下呼吸道、上下消化道、泌尿生殖道手术或经以上器官手术,如经口腔部大手术、经阴道子宫切除术、经直肠前列腺手术，及开放性骨折或创伤手术感染后果严重(ConsequenceofSSISevere)血管手术、心脏手术、开颅手术、门脉高压症手术使用人工材料或人工装置的清洁手术类切口及严重污染类切口，应治疗性使用抗菌药物，不属于预防,外科围术期抗生素预防性应用-用不用？,外科围术期抗生素预防性应用,用不用?-预防用药的指证用什么?-选择抗菌药物的原则何时用?-用药时机怎么用?-用药途径用几次?-用药次数,手术部位感染预防-抗生素选用时应考虑,选择的抗生素应覆盖常见病原菌不同部位的常见病原差别不同地区与不同年代的耐药性变迁良好大的药代动力学特性价格低,毒性小青霉素和头孢菌素过敏病人的替代方案,RelativeDistributionofBacteriaFromSuperficialtoDeepInfections,StaphylococcusStreptococcus,Gram-negativeBacilli,Anaerobes,Superficialinfection,Deepinfection,NicholsRL,etal.ClinInfectDis.2001;33(suppl2):S84-S93.,手术类型、SSI常见病原菌及预防用药选择,临床常见手术围术期抗生素种类选择,SIGN（ScottishIntercollegiateGuidelineNetwork）,Ceftriaxoneversusothercephalosporinsforperioperativeantibioticprophylaxis:ameta-analysisof43RCT.,比较头孢曲松对其它头孢菌素-19861996年文献43篇13482例-外科手术切口感染13303例,RR98.3%;CI:0.550.89减低感染30%-泌尿道感染8865例,RR0.66,98.3%;CI为0.430.67(CDC定义:0.361.12)-呼吸道感染9567例RR0.81,98.3%;CI为0.611.09结论:对污染手术头孢曲松优于其他头孢菌素,对其他手术,则无显著差异,DietrichES,etal.Chemotherapy2002;48:4956,过敏患者的抗菌药物替代方案,病人对青霉素过敏不宜使用头孢菌素时-针对葡萄球菌、链球菌可用克林霉素-针对革兰阴性杆菌可用氨曲南,或二者联合应用氨基糖苷类因其价廉易得-在我国耐药情况不严重的基层医院,在密切监控不良反应情况下,氨基糖苷类抗生素(庆大霉素、阿米卡星)仍有实用价值万古霉素一般不作预防用药-除非已证明有MRSA所致的SSI流行时喹诺酮类一般不宜用作预防用药关键问题：是否确实存在过敏反应,外科围术期抗生素预防性应用,用不用?-预防用药的指证用什么?-选择抗菌药物的原则何时用?-用药时机怎么用?-用药途径用几次?-用药次数,WittmannDHetal,JournalofChemotherapy,vol9,suppl2,p19-33,1997,“Bolusdose30minutesbeforetheskinincision”,Timeofantibioticadministration,PerioperativeProphylacticAntibioticsTimingofAdministration,Infections(%),HoursFromIncision,14/369,5/699,5/1009,2/180,1/81,1/41,1/47,15/441,2847例选择性清洁或清洁污染切口,抗生素应该在皮肤切开前半小时或麻醉诱导开始时,ClassenDC,etal.NEJM1992;326(5):281286,外科围术期抗生素预防性应用,用不用?-预防用药的指证用什么?-选择抗菌药物的原则何时用?-用药时机怎么用?-用药途径用几次?-用药次数,采用怎样给药途径,静脉口服或经肌肉注射给药-药物吸收的个体差异-不能保证有效血浆浓度-不主张,外科围术期抗生素预防性应用,用不用?-预防用药的指证用什么?-选择抗菌药物的原则何时用?-用药时机怎么用?-用药途径用几次?-用药次数,AppropriateDurationofProphylaxis,多剂给药与单剂并无明显优越性Noclearadvantageofeithersingledoseormultipledoses1多数手术预防用药都应小时24小时Prophylaxislessthan24hoursindicatedformostprocedures2,1McDonaldM,etal.AustNZJSurg.1998;68:388-396.2AmJHealth-SystPharm.1999;56:1839-1888.,AppropriateDurationofProphylaxis,血管手术（Vascular）Recommendation:24hours1心胸外科（Cardiothoracic）Prospectivenon-randomizedtrialof353patients2单剂VS48小时Singledosevs.48hours感染率无差别NosignificantdifferenceininfectionrateProspectiveobservationalstudyof2,641patients3短时间VS长时间Short(48hours)感染风险无差别Nodifferenceinriskofinfection长疗程增加耐药风向Increasedriskofresistanceinlongcourse,1AmJHealth-SystPharm.1999;56:1839-1888.2BucknellSJ,etal.AustNZJSurg.2000;70:409-411.3HarbarthS,etal.Circulation.2000;101:2916-2921.,AppropriateDurationofProphylaxis,实体脏器移植SolidOrganTransplant研究不充分Insufficientstudies推荐Recommendations心肺Heart/Lungtransplantation:48to72hours肝脏Livertransplantation:48hours肾脏Kidneytransplantation:singledose,AmJHealth-SystPharm.1999;56:1839-1888.,Re-Dosing,如果下列情况可以考虑追加抗生素Considerre-dosingantibioticsif:手术时间3小时以及抗生素为短效Procedure3hoursandantibioticisshort-acting长时间或过量出血Prolongedorexcessivebleedingduringprocedure存在导致抗生素半衰期缩短的因素Factorspresentthatmayshortenhalf-lifeoftheantimicrobial(e.g.,excessiveburns),AmJHealth-SystPharm.1999;56:1839-1888.,BohnenJM,etal.ArchSurg.1992;127:83-89.,GuidelinesforClinicalCareSurgicalInfectionSocietyPolicyStatement,无需延长抗生素治疗NoProlongedAntibioticTherapy早期急性阑尾炎（EarlyAcuteAppendicitis）急性化脓性阑尾炎（AcuteSuppurativeAppendicitis）急性单纯性胆囊炎（SimpleAcuteCholecystitis）单纯性缺血性肠病（未穿孔）SimpleIschemicBowel(noperforation)胃十二指肠溃疡穿孔（24h）GastroduodenalUlcerPerforation(24h)外伤性肠穿孔（12h）TraumaticEntericPerforation(12hours),外科围术期抗生素预防性应用,用不用?-预防用药的指证用什么?-选择抗菌药物的原则何时用?-用药时机怎么用?-用药途径用几次?-用药次数,寻找新的抗感染药物-新药越来越少限制人以外(畜牧业)使用-减少对人类的影响优化抗感染药物预防VS治疗加强抗感染药物的临床管理加强医院感染的控制-减少耐药菌传播,细菌耐药的临床对策-MeasurestoResistance,-减少抗生素选择性压力,AntibioticStewardshipinHospitals,Typesofstewardship,11.Cycling/rotation12.Therapeuticsubstitution13.Formularyintervention（restriction/add-on）,1.Generaleducation2.Guidelines3.Clinicalpathway4.Expertapprovalofrestricteddrugs5.Review/recommendchangestoAbxtherapy6.Therapeuticdrugmonitoring7.Auditandfeedback8.Compulsoryorderformsforrestricteddrugs9.Compulsoryinteractivecomputerorderform10.Automaticantibioticstop-orderpolicy,“thedominantlessonofhistoryisthatmankindisunteachable.”,-WinstonChurchill,RoleofEducationAlone?,Typesofstewardship,11.Cycling/rotation12.Therapeuticsubstitution13.Formularyintervention（restriction/add-on）,1.Generaleducation2.Guidelines3.Clinicalpathway4.Expertapprovalofrestricteddrugs5.Review/recommendchangestoAbxtherapy6.Therapeuticdrugmonitoring7.Auditandfeedback8.Compulsoryorderformsforrestricteddrugs9.Compulsoryinteractivecomputerorderform10.Automaticantibioticstop-orderpolicy,及时的临床会诊有效的临床会诊,专家资源匮乏和临床需要差距！,抗菌药物分级管理制度的建立和实施,Typesofstewardship,11.Cycling/rotation12.Therapeuticsubstitution13.Formularyintervention（restriction/add-on）,1.Generaleducation2.Guidelines3.Clinicalpathway4.Expertapprovalofrestricteddrugs5.Review/recommendchangestoAbxtherapy6.Therapeuticdrugmonitoring7.Auditandfeedback8.Compulsoryorderformsforrestricteddrugs9.Compulsoryinteractivecomputerorderform10.Automaticantibioticstop-orderpolicy,建立预警机制听证与反馈限制类药物强制性处方申请强制性交互式处方申请自动停止医嘱,Typesofstewardship,11.Cycling/rotation12.Therapeuticsubstitution13.Formularyintervention（restriction/add-on）,1.Generaleducation2.Guidelines3.Clinicalpathway4.Expertapprovalofrestricteddrugs5.Review/recommendchangestoAbxtherapy6.Therapeuticdrugmonitoring7.Auditandfeedback8.Compulsoryorderformsforrestricteddrugs9.Compulsoryinteractivecomputerorderform10.Automaticantibioticstop-orderpolicy,X,处方干预（formularyintervention）,根据细菌耐药的具体问题，调整医院处方集，改变耐药现状,优化抗菌药物临床管理OptimizingAntibioticstewardship,处方干预（formularyintervention）之处方限制（formularyrestriction）-限制使用某种或某类抗菌药物做为一种策略有助于减少细菌耐药性、不良反应以及费用1-尤其在耐药菌感染爆发流行时有效，如同时加强感染控制措施和对医生进行教育则效果更为明显-限制使用的抗菌药物常为广谱抗生素、快速出现耐药和容易出现毒性者-方法学问题-很难证明限制处方能从整体上控制细菌的耐药，限制使用某种或某类抗菌药物使其耐药性减低，但非限制使用药物则耐药性可能增加,KollefMH,FraserVJ:Antibioticresistanceintheintensivecareunit.AnnInternMed2001:134:298-314,优化抗菌药物临床管理OptimizingAntibioticstewardship,19831988年间沈阳地区大量应用头孢噻肟19901991年间院内下呼吸道感染肠杆菌科细菌耐药达42.9%.停用头孢噻肟4年重新评价头孢噻肟的敏感性时间:1996.011997.12研究对象:院内下呼吸道感染痰培养获得革兰阴性杆菌345株结果：肠杆菌科细菌对头孢噻肟耐药率由42.9%降至13.44%。,限制使用头孢噻肟使肠杆菌科细菌对其敏感性恢复,中国医大一院资料,处方干预（formularyintervention）之处方限制（formularyrestriction）,OptimizingAntibioticManagementStrategies,处方干预（formularyintervention）之处方追加（formularyadd-on）,根据细菌耐药的具体问题，调整医院处方集使临床有更多的选择余地，改变耐药现状,CMSS：绿脓杆菌的敏感性变迁,2008CMSSDataonfile,优化抗菌药物临床管理OptimizingAntibioticstewardship,TraditionalantibioticsareoftenlinkedtoemergenceofMDRgram-negativebacteria-non-fermentorsThereisaneedforaneffective,non-antipseudomonalcarbapeneminseriousinfectionscausedbyMDRgram-negativepathogens(withouttheneedforPseudomonascoverage).,AdaptedfromJacobyGA,Munoz-PriceLS.NEnglJMed.2005;352(4):380391;HammondML.JAntimicrobChemother.2004;53(supplS2):ii7ii9;LivermoreDM.ClinMicrobiolInfect.2004;10(suppl4):19;LivermoreDM.LancetInfectDis.2005;5:450459;ParamythiotouE,etal.ClinInfectDis.2004;38:670677.,MDR革兰阴性菌/碳青霉稀耐药铜绿逐渐增加呼唤不具抗假单胞菌活性碳氢霉烯,DAgataE.ICHE2004,PatersonDL.AnnInternMed,ErtapenemPharmacokinetics:MinimalSelectivityforResistantPaeruginosaUnderClinicalConditions,MinimalresistanceselectionamongPaeruginosa(MIC90:16mg/L)MinimalresistanceselectionamongEnterobacteriaceae(MIC90:0.03mg/L),N=68healthyvolunteers,MRSA=methicillin-resistantSaureus;MSSA=methicillin-susceptibleSaureus.AdaptedfromNixDE,etal.JAntimicrobChemother.2004;53(supplS2):ii23ii28;FriedlandI,etal.JChemother.2002;14(5):483491.,PlasmaErtapenemConcentration,mg/L,TotalFree,0.01,0.1,1000,1,10,100,0,4,8,12,16,20,24,MIC90,mg/LOrganism16Paeruginosa,enterococci,MRSA1.0Anaerobes0.25MSSA,pneumococci0.12GroupAstreptococci0.03Enterobacteriaceae,HoursAfter1gIntravenousDoseofErtapenem,ErtapenemEffectsonHospitalEcologyinClinicalMonitoringStu