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首页 抗生素合理应用全

抗生素合理应用全.ppt

抗生素合理应用全

DNSJDS
2019-04-14 0人阅读 举报 0 0 暂无简介

简介:本文档为《抗生素合理应用全ppt》,可适用于医药卫生领域

PUMCHospital急诊科抗生素的合理应用*PUMCHospitalDepofEmergencyMedicine【粉乖留爪】内容感染的有关概念抗生素的分类时间依赖型抗生素的药动学药效学参数临床常见抗生素的药动学药效学参数目前临床上抗生素的给药方式不规范的给药方式所导致的后果急诊科抗生素的合理应用DepofEmergencyMedicine【粉乖留爪】*今天我要讲的主要内容包括:照读幻灯片PUMCHospitalDepofEmergencyMedicine【粉乖留爪】合理使用抗生素的概念合理使用抗生素的临床药理概念为安全有效使用抗生素即在安全的前提下确保有效这就是合理使用抗生素的基本原则。首先要掌握抗生素的抗菌谱根据致病菌的敏感度选择抗生素根据感染疾患的规律及其严重程度选择抗生素,重症深部感染选择抗菌作用强血与组织浓度均较高的抗生素根据抗菌药物的药动学特点选择抗生素严格掌握适应症DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】全身性感染的概述  按传统习惯全身性感染指ldquo弥散性感染rdquo(disseminatedinfection) 全身性感染是感染引起的全身炎  症反应综合征(年)DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】 全身性感染是多脏器功能障碍综合征(MODS)的重要原因。 至年间北京协和医院ICU收治名危重病患者其中MODS 余名由严重感染诱发者占。DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】 流行病学调查 非心脏ICU患者的首要死亡原因 年死亡率与心肌梗塞相同 在美国人口的所有死因中居第位  每年约,例严重感染  发病率:  每年死亡者超过,例  死亡率:约%常见的致死率高的临床综合征DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】全身性感染发展趋势人口老龄化(不仅限于西方国家)医疗水平提高生命支持治疗发展免疫功能低下(肿瘤治疗、器官移植)介入性技术和装置推广应用细菌耐药性与院内感染增多DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】全身性感染:与其它主要疾病相比daggerNationalCenterforHealthStatistics,sectAmericanCancerSociety,*AmericanHeartAssociationDaggerAngusDCetalCritCareMedAIDS*ColonBreastCancersectCHFdaggerSevereSepsisDaggerCases,严重感染的发病率严重感染的死亡率AIDS*SevereSepsisDaggerAMIdaggerBreastCancersectDepofEmergencyMedicine【粉乖留爪】*Angusetalstudiedtheincidence,cost,andoutcomeofseveresepsisintheUnitedStatesInastudybasedonstatehospitaldischargerecordsfromlargestateswithpopulationandhospitaldatafromtheUSCensus,CentersforDiseaseControl,HCFA,andtheAmericanHospitalAssociation,theinvestigatorsgeneratednationalsepsisdataInthisstudy,theyreportthattheincidenceofseveresepsisiscases,populationAsshownontheslide,thisissignificantlygreaterthantheincidenceofotherwellrecognizeddiseasesasreportedbytheAmericanHeartAssociationSimilarly,Angusetalreportedthattheannualmortalityofseveresepsisinwas,AccordingtotheAmericanHeartAssociation,thisisvirtuallyidenticaltothenumberofpeopleintheUSwhodiesuddenlyofcoronaryheartdiseasewithoutbeinghospitalizedAmericanCancerSocietyStatisticsAvailableat:wwwcancerorgonAmericanHeartAssociationHeartandStrokeStatisticalUpdateDallas,Tex:AmericanHeartAssociation,AngusDC,LindeZwirbleWT,LidickerJ,etalIncidence,cost,outcomeofseveresepsisintheUnitedStatesCritCareMed(InPress)NationalCenterforHealthStatisticsFastStats(AIDSHIV)Availableat:wwwcdcgovnchsfastatsaidshivhtmonPUMCHospitalDepofEmergencyMedicine【粉乖留爪】*AngusDCCritCareMed严重感染:临床的重大挑战目前DepofEmergencyMedicine【粉乖留爪】*InthestudybyAngusetaldescribedonthepreviousslide,thenationalestimateofseveresepsiswas,casesSincethisfigurewasbasedondata,itisestimatedthattherewillbemorethan,casesthisyearBasedondatafromtheUScensus,AngusetalestimatethatthenumberofcasesofseveresepsiswillincreasesteadilyatperannumThisincreaseintheincidenceofseveresepsisisgreaterthantheanticipatedpopulationgrowthThedisproportionategrowthisduetothehighincidenceofsepsisinolderpatientsandadisproportionateincreaseinthenumberofelderlyAmericans(ldquograyingrdquoofAmerica)AngusDC,LindeZwirbleWT,LidickerJ,etalIncidence,cost,outcomeofseveresepsisintheUnitedStatesCritCareMed(InPress)PUMCHospitalDepofEmergencyMedicine【粉乖留爪】全身性感染的相关概念进展DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】ACCPSCCM联席会议定议感染对微生物的炎症反应,或微生物对正常无菌组织的入侵全身炎症反应综合症(SIRS)体温、呼吸、脉搏及血像全身性感染(sepsis)感染加SIRS诊断标准严重感染(severesepsis)全身性感染器官功能不全感染性休克全身性感染扩容后仍低血压多器官功能不全综合症(MODS)BoneRCetalChest:DepofEmergencyMedicine【粉乖留爪】*TheAmericanCollegeofChestPhysicians(ACCP)andSocietyofCriticalCareMedicine(SCCM)heldaconsensusconferenceinAugusttoagreeonasetofdefinitionsthatcouldbeappliedtopatientswithsepsisandorgandysfunctionTheconsensuspanelalsorecommendedtheuseofseverityscoringmethodstocharacterizethediseaseanddevelopacomprehensivemodelforthesyndromeThisslideprovidesabriefdefinitionofthevariouscomponentsofthesepsissyndromeNotably,thisisanonlinearprocessratherthanacontinuumandthepresenceoforgandysfunctionidentifiesapopulationwithasignificantriskofmortalityBoneRC,BalkRA,CerraFB,etalDefinitionsforsepsisandorganfailureandguidelinesfortheuseofinnovativetherapiesinsepsisChest:PUMCHospitalDepofEmergencyMedicine【粉乖留爪】全身性感染:一个复杂的疾病Chest:CritCareMed:SDepofEmergencyMedicine【粉乖留爪】*Thisconceptualframeworkshowstheinterrelationshipsbetweeninfection,noninfectiousdisorders,SIRS,sepsis,andseveresepsisComponentsoftheprocessnotdiscussedonthefollowingslidesinclude:Infection:amicrobialphenomenoncharacterizedbyaninflammatoryresponsetothepresenceofmicroorganismsortheinvasionofnormallysterilehosttissuebythoseorganismsBacteremia:thepresenceofviablebacteriainthebloodstreamSepticshock:sepsisinducedhypotensiondespiteadequatefluidresuscitationalongwiththepresenceofperfusionabnormalitiesthatmayinclude,butarenotlimitedto,lacticacidosis,oliguria,oranacutealterationinmentalstatusMultipleorgandysfunctionsyndrome(MODS):presenceofalteredorganfunctioninanacutelyillpatientsuchthathomeostasiscannotbemaintainedwithoutinterventionInflammationandhemostasisaretightlylinkedTherefore,althoughnotshownonthisslide,sepsisandseveresepsislieonabackgroundofdisturbedhemostasisBoneRC,BalkRA,CerraFB,etalDefinitionsforsepsisandorganfailureandguidelinesfortheuseofinnovativetherapiesinsepsisChest:OpalSM,ThijsL,CavaillonJM,etalRelationshipsbetweencoagulationandinflammatoryprocessesCritCareMed:SPUMCHospitalDepofEmergencyMedicine【粉乖留爪】SIRSSIRS:个以上下述条件体温degC或degCHR呼吸minWBC数,mLor,mLor未成熟中性粒细胞BoneRCetalChest:DepofEmergencyMedicine【粉乖留爪】*Thesystemicinflammatoryresponsesyndrome(SIRS)isaclinicalresponsearisingfromanonspecificinsultmanifestedbytwoormoreofthefollowing:FeverorhypothermiaTachycardiaTachypneaLeukocytosis,leukopenia,oraleftshift(increaseinimmatureneutrophilicleukocytesintheblood)RecentevidenceindicatesthathemostaticchangesplayasignificantroleinmanySIRSlinkeddisordersBoneRC,BalkRA,CerraFB,etalDefinitionsforsepsisandorganfailureandguidelinesfortheuseofinnovativetherapiesinsepsisChest:OpalSM,ThijsL,CavaillonJM,etalRelationshipsbetweencoagulationandinflammatoryprocessesCritCareMed:SPUMCHospitalDepofEmergencyMedicine【粉乖留爪】全身性感染:不仅仅是炎症反应全身性感染:确认或怀疑有感染个或多个SIRS标准BoneRCetalChest:DepofEmergencyMedicine【粉乖留爪】*TheoriginalACCPSCCMcriteriaforthediagnosisofsepsisrequiredthepresenceofknownorsuspectedinfectionplustwoormoreSIRScriteriaClimbingaflightofstairscanproducetwoSIRScriteria(tachypnea,tachycardia)inanormalsedentaryindividualThus,clinicalstudiesofsepsisgenerallyrequireatleastthreeSIRScriteriaplusknownorsuspectedinfectionforentryBoneRC,BalkRA,CerraFB,etalDefinitionsforsepsisandorganfailureandguidelinesfortheuseofinnovativetherapiesinsepsisChest:PUMCHospitalDepofEmergencyMedicine【粉乖留爪】严重感染严重感染:全身性感染伴有个以上器官功能不全心血管肾脏呼吸肝血液CNS无法解释的代谢性酸中毒BoneRCetalChest:DepofEmergencyMedicine【粉乖留爪】*Severesepsisissepsisplussignsandsymptomsofacuteorgandysfunction,hypoperfusion,orhypotensionHypoperfusionandperfusionabnormalitiesmayinclude,butarenotlimitedto,lacticacidosis,oliguria,oranacutealterationinmentalstatusAsshownonthenextslide,organdysfunctionmayinvolveanyofthefollowingaloneorincombination:CardiovascularsystemKidneyRespiratorysystemLiverHematologic(blood,coagulation)CentralnervoussystemPresenceofanotherwiseunexplainedmetabolicacidosisBoneRC,BalkRA,CerraFB,etalDefinitionsforsepsisandorganfailureandguidelinesfortheuseofinnovativetherapiesinsepsisChest:PUMCHospitalDepofEmergencyMedicine【粉乖留爪】感染创伤SIRS全身性感染严重感染MODS感染引起的SIRS全身性感染的演变过程具有二项以上下列临床表现:体温geoCorleoC心率ge次分呼吸频率ge次分白细胞计数ge,mm或le,mm或幼粒细胞DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】器官功能不全的表现心动过速低血压CVPPAOP黄疸肝酶白蛋白PT神志改变昏迷精神异常呼吸急促PaOmmHgSaOPaOFiO少尿无尿血肌酐血小板PTAPTTDdimerDepofEmergencyMedicine【粉乖留爪】*Followingidentificationofapatientwithsepsis,theclinicianmustassessthepatientforthepresenceofacuteorgandysfunction(severesepsis)ThepresenceofacuteorgandysfunctionisoftenrecognizedclinicallybythepatientrsquospresentingsignsandsymptomsHowever,insomeinstanceslaboratorydataorresultsofinvasivemonitoringwillconfirmthediagnosisoforgandysfunctionTheillustrationofthepatientonthisslidehasarrowspointingtovariousorgansthatmightprovidecluestothepresenceoforgandysfunctionIndicationsoforgandysfunctioninclude:Centralnervoussystem:alteredconsciousness,confusion,psychosis,deliriumRespiratorysystem:tachypnea,hypoxemia,oxygensaturation,decreasedratioofarterialoxygenvsinspiredoxygenLiver:jaundice,increasedliverenzymes,hypoalbuminemia,increasedprothrombintimeCardiovascular:tachycardia,hypotension,increasedcentralvenouspressure,increasedpulmonaryarteryocclusivepressureKidney:oliguria,anuria,increasedcreatinineHematological:thrombocytopenia,abnormalcoagulationtests,decreasedlevelsofProteinC,increasedDdimersPUMCHospitalDepofEmergencyMedicine【粉乖留爪】严重感染的常规治疗感染源的控制抗菌素循环支持机械通气肾脏替代治疗镇静止痛营养支持血制品其它WheelerAP,BernardGRNEnglJMed:DepofEmergencyMedicine【粉乖留爪】*Standardcareofthepatientwithseveresepsisconsistsofanumberofmedical(andsometimessurgical)interventionsintendedtonormalizephysiologyandeliminateinfectionThesearedividedinto:Sourcecontrol:ThistermreferstomanagementofthesourceoftheinfectionItcanconsistofsurgerytodrainanabscessorremovalofaninfectedcatheterAntibiotics:Whiletheinitialtherapymaybebroadbasedandempiric,identificationofthespecificpathogenbymicrobiologicstudiesmayresultinaswitchoftheantibiotictothosethatarethemostspecificandbacteriocidalHemodynamicsupport:Thistermreferstovolumereplenishmenttherapyfollowed,whennecessary,byappropriateuseofdrugssuchasnorepinephrinetomaintainbloodpressureandorganperfusionMechanicalventilation:RespiratoryfailureisacommonmanifestationofpulmonaryorgandysfunctioninpatientswithseveresepsisMechanicalventilationisinstitutedtoincreaseoxygenationandimprovegasexchangeRenalreplacementtherapy:ImpairedrenalfunctionisasignoforgandysfunctioninpatientswithseveresepsisRenalreplacementtherapyconsistsoftemporaryhemodialysisorultrafiltrationSedationandanalgesia:SedationisoftenrequiredtotreatanxietyandagitationinpatientswithseveresepsisBecausethesepatientsareatriskforpainandphysicaldiscomfort,analgesicsalsoarecommonlyemployedEnsureadequatenutrition:SepsisisahypercatabolicstateTherefore,caloricandnitrogenrequirementsshouldbemetandenteralnutritionprovidedinatimelyfashionProvidehematologicalsupport:Criticallyillpatientsmayrequirepackedredbloodcells,platelets,andcoagulationfactorsOthersupportivemeasures:Theseincludemeasurestopreventdeepvenousthrombosis,stressulcerprophylaxis,etcWheelerAP,BernardGRTreatingpatientswithseveresepsisNEnglJMed:PUMCHospitalDepofEmergencyMedicine【粉乖留爪】抗生素使用理想目标有效控制感染达到最佳疗效有效预防和减少抗生素的毒副作用剂量和疗程合理防止产生耐药菌株避免导致病人体内正常菌群失调选药、给药途径、给药方式合理。DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】目前临床抗生素使用情况普遍、大量、长时间、不规范地预防性使用抗菌药物药物资源浪费巨大不重视、不了解抗生素药物的药动学药效学随意制订给药剂量、途径、分配方案和疗程使很多抗菌药物没有发挥应有的作用抗菌药物滥用不但是造成医药费用增加的重要原因同时还可引发大量耐药菌产生对社会造成危害DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】抗菌药物-按杀菌活性分类时间依赖型抗生素浓度依赖型抗生素DepofEmergencyMedicine【粉乖留爪】*抗生素按杀菌活性可分成二类:时间依赖型浓度依赖型PUMCHospitalDepofEmergencyMedicine【粉乖留爪】抗菌药物-按杀菌活性分类第一大类:时间依赖杀菌作用持续后效应无或轻、中度b内酰胺类(青霉素类、头孢菌素、氨曲南、碳烯类)克林和大环(红、克)、四环、链、万古在MIC倍时杀菌率即处于饱和杀菌范围主要依赖于接触时间血药浓度超过MIC时间(TMIC)是与临床疗效相关的主要参数PAE(postantibioticeffect):PAE也称抗生素作用后效应:是指在体外经短时间接触药物后细菌延迟再生长的时间DepofEmergencyMedicine【粉乖留爪】*时间依赖型的抗生素主要的一大类就是b内酰胺类(青霉素类、头孢菌素、氨曲南、碳烯类)克林和大环(红、克、阿奇)、四环、链、万古是目前临床上应用最多的一些抗生素它有以下特点:持续后效应无或轻、中度在MIC倍时杀菌率即处于饱和杀菌范围主要依赖于接触时间血药浓度超过MIC时间是与临床疗效相关的主要参数PUMCHospitalDepofEmergencyMedicine【粉乖留爪】抗菌药物-按杀菌活性分类第二大类:浓度依赖杀菌作用药物持续后效应氨基糖苷类和喹诺酮类甲硝唑投药目标达到最大药物接触药物浓度越高杀菌率及杀菌范围也越大小时AUC(浓度时间曲线下面积)MIC、峰浓度MIC是疗效相关的主要参数DepofEmergencyMedicine【粉乖留爪】*浓度依赖型的抗生素包括氨基糖苷类和喹诺酮类甲硝唑它有以下几个特点投药目标达到最大药物接触药物浓度越高杀菌率及杀菌范围也越大小时AUC(浓度时间曲线下面积)MIC、峰浓度MIC是疗效相关的主要参数PUMCHospitalDepofEmergencyMedicine【粉乖留爪】时间依赖杀菌浓度依赖杀菌抗生素后效应细菌数量死亡率症状和体征的识别抗菌药物在体内的作用主要决定于药代动力学和MIC时间浓度TotalFreeMICDudleyMN,GriffithDAnimalmodelsofinfectionIn:NightingaleCH,MurakawaT,AmbrosePG,edsAntimicrobialPharmacodynamicsinTheoryandPracticestedNewYork,NY:MarcelDekker药动学药效学起效剂量抗菌药物在体内起效的过程溶解吸收分布代谢排泄DepofEmergencyMedicine【粉乖留爪】*ThissliderepresentskeyfactorsinvolvedinantimicrobialtherapyOncethedoseisadministered,pharmacokineticparametersthendescribewhathappenstothedrugonceitentersthebodyAbsorptionfromtheGItractisessentialfororaltherapyOnceinthebloodstreamcriticalfactorsforsuccessincludedistributionofthedrugintotheinfectedtissuesHowlongadrugremainsinthebloodstreamisdeterminedbyhalflife(metabolismorexcretion)Thedistributionandmetabolismofthedrugcanhaveanimpactonsafety(hepaticmetabolites)orefficacy(urineexcretionunchangedforUTI)ThedegreeofproteinbindingcanimpactthemicrobiologicactivityPharmacodynamicsrepresentstherelationshipbetweenthepharmacologicactivity(MIC)andpharmacokinetics(AUCorpeakconcentrations)Thepharmacologicactivityofanantibioticcanbedefinedbywhethertheyaretimedependent,(effectcanbepredictedbytimeabovetheMIC,orconcentrationdependenthighertheconcentrationthegreaterthebacterialkilling)asdefinedbypeak:MICorAUC:MICratiosInaddition,postantibioticeffect(PAE)orthecontinuedbacterialkillingwhentheantibioticbloodlevelfallbelowtheMICcanalsoimpactefficacyPharmacologiceffectcanbedeterminedbyadeclineinbacterialcolonycountswhichistypicallyobservedininvitromodelsMortalityratesinanimalstudiesisanotherendpointandfinallyinhumantrials,resolutionofsignsandsymptomsofaninfectiontypicallydeterminesclinicalsuccessratesPUMCHospitalDepofEmergencyMedicine【粉乖留爪】抗菌药物合理应用的药效学考虑药动学药效学参数与抗菌效力(动物模型)TMIC:血浆浓度高于细菌MIC值的时间hrAUCMIC:小时浓度时间曲线下面积与MIC比值峰值MIC:血浆峰浓度与MIC比值DepofEmergencyMedicine【粉乖留爪】参数药物高于MIC时(TMIC)青、头孢、碳青烯、氨曲、大环、克林hrAUCMIC氨基糖苷、氟喹酮、阿奇峰值MIC四环、万古、链阳、氨基糖苷、氟喹酮*不同的抗生素的抗菌效力参照的药动学药效学参数不一样。青、头孢、碳青烯、氨曲、大环克林参照(TMIC)氨基糖苷、氟喹酮、阿奇参照hrAUCMIC四环、万古、链阳、氨基糖苷、氟喹酮参照峰值MIC名词解释:TMIC:血浆浓度高于细菌MIC值的时间hrAUCMIC:小时浓度时间曲线下面积与MIC比值峰值MIC:血浆峰浓度与MIC比值PUMCHospitalDepofEmergencyMedicine【粉乖留爪】药效学及药代动力学重要参数时间依赖型的抗生素TMIC:血药浓度超过MIC的维持时间TMIC:血药浓度超过MIC的维持时间与给药间隔时间的比值即MIC时间浓度DepofEmergencyMedicine【粉乖留爪】*名词解释:TMIC:血浆浓度高于细菌MIC值的时间TMIC:血浆浓度高于细菌MIC值的时间与该药给药间隔(时间)的比值PUMCHospitalDepofEmergencyMedicine【粉乖留爪】内酰胺类:血药浓度高于MIC时间最主要参数给药间期并不需要都超过MICTMIC~-起效TMIC~mdash保证有效细菌清除药效学及药代动力学重要参数时间依赖型的抗生素DepofEmergencyMedicine【粉乖留爪】*照幻灯片读。强调以往一直认为TMIC但目前认为TMIC就能保证有效的细菌清除为什么会把TMIC定在请下面的两个实验结果PUMCHospitalDepofEmergencyMedicine【粉乖留爪】TimeaboveMIC()BacteriologicCure()药效学及药代动力学重要参数时间依赖型的抗生素肺炎链球菌感染动物的模型青霉素头孢菌素有效的细菌清除:青霉素:TMIC头孢菌素:TMICDepofEmergencyMedicine【粉乖留爪】*图示横轴表示TMIC,纵轴表示细菌清除率。大家可以看到当TMIC以后细菌清除率达到随着TMIC的增加细菌清除率仍在增加但增加的速度比前面减缓。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】TimeaboveMIC()Mortalityafterdaysoftherapy()药效学及药代动力学重要参数时间依赖型的抗生素肺炎链球菌感染动物的模型青霉素头孢菌素有效的细菌清除:青霉素:TMIC头孢菌素:TMICDepofEmergencyMedicine【粉乖留爪】*反过来看图示横轴表示TMIC纵轴表示治疗天后病人的死亡率。大家可以看到随着TMIC增加病人的死亡率在不断减少当TMIC病人的死亡率降到底线再增加TMIC的数值死亡率不再下降。所以综述以上二个图说明了TMIC是一个重要的界点。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】临床常见抗生素药动学药效学特点以及主要药效学参数DepofEmergencyMedicine【粉乖留爪】PUMCHospitalDepofEmergencyMedicine【粉乖留爪】临床常见头孢菌素的半衰期头孢西丁头孢甲肟头孢孟多头孢噻肟头孢呋辛头孢磺啶头孢唑肟头孢唑啉头孢他啶头孢派酮拉他头孢头孢替坦头孢曲松克静脉注射小时TfracKnotheetal,头孢曲松是半衰期最长的头孢菌素:~小时平均小时DepofEmergencyMedicine【粉乖留爪】*罗氏芬是半衰期最长的头孢菌素:~小时平均小时。临床常用头孢菌素给予静注克后只有罗氏芬半衰期长达小时其他头孢菌素半衰期大多数在小时之间PUMCHospitalDepofEmergencyMedicine【粉乖留爪】头孢曲松PDPK特点半衰期长(h)蛋白结合率高()但容易饱和随着剂量增加游离浓度增加单次给药可产生相对较高的游离浓度DepofEmergencyMedicine【粉乖留爪】*照读幻灯片。需要澄清的是罗氏芬的蛋白结合率高但蛋白结合力并不强罗氏芬与蛋白结合是可逆的。并且随着剂量增加容易饱和所以有相对较高的游离浓度。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】头孢曲松mdash半衰期最长的头孢菌素头孢曲松半衰期长的机理一、由于含三嗪环罗氏芬与血浆蛋白的结合率高达~%二、罗氏芬体内不代谢、不通过肾小管主动分泌Dudley,Kowalskyetal,Stoeckeletal,aL黷hy,Richardsetal,Bergan,Bergan,Fraschinietal,Nakashimaetal,Richardsetal,DepofEmergencyMedicine【粉乖留爪】*罗氏芬长半衰期的主要由其三嗪环上烯醇式阴离子基团所决定。同时罗氏芬体内不代谢也不通过肾小管主动分泌也使其半衰期延长。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】头孢曲松静脉单次给药公斤体重成年人注射g药物后总的药物浓度和游离药物浓度超过MIC的时间(TMIC)与MICAA:MIC的资料取自Widderman和Atkinson,其中流感嗜血杆菌和肺炎链球菌的MIC取自Neu等。B:药代动力学资料取自Vozeh等。C:这个数值很高一般说头孢曲松和头孢噻肟对金黄色葡萄球菌的MIC差别不会这么大。Pfaller等()测得头孢曲松对苯甲异恶唑青霉素敏感的金黄色葡萄球菌的MIC是DepofEmergencyMedicine【粉乖留爪】*头孢曲松(罗氏芬)和头孢噻肟静脉单次给药对于临床常见的致病菌罗氏芬TMIC都在小时以上所以罗氏芬TMIC。而头孢噻肟TMIC基本在小时左右头孢噻肟必须每小时给药一次。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】主要抗菌药物的药效学参数DepofEmergencyMedicine【粉乖留爪】Sheet半衰期药物方案肺炎球菌(中介)肺炎球菌(高耐)MICTMICMICTMIC小时青霉素MuqHmdashmdashmdashmdash小时头孢噻肟qhmdashmdashmdash小时头孢曲松qhmdashmdashmdashSheetSheet*对于耐药的肺炎链球菌来说要达到TMIC:对于半衰期小时的抗生素来说例如青霉素它的给药方案必需是Mu,qh。对于半衰期在小时之间的抗生素来说例如头孢噻肟它的给药方案必需是,qh。对于半衰期小时的抗生素来说例如头孢曲松(罗氏芬)它的给药方案是,qh。反过来说要达到TMIC只有罗氏芬的给药方式可以一天一次其他短半衰期的抗生素如果它也按一天一次这样给药它的TMIC不能达到也就是说不能保证有效的细菌清除。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】目前临床使用抗生素的现状DepofEmergencyMedicine【粉乖留爪】*PUMCHospitalDepofEmergencyMedicine【粉乖留爪】青霉素万u,bid青霉素万u,qh西力欣g,Bidg,qd西力欣g,qh凯福隆g,Bid凯福隆g,qh头孢拉定g,qd,Bid头孢拉定g,qhBid=qhTid=qh医护人员认知不足:各种药物的特性规范用药的重要性如果医生完全规范给药实际上有阻力:造成护士的工作量增加门急诊的病人顺应性差一天一剂使用的药物方便有效经济DepofEmergencyMedicine【粉乖留爪】*请看右边绿色的圈蓝色的字代表目前我们临床上常见抗生素的用法红色的字代表准确的给药方式:青霉素helliphellip正确的给药方式应该是helliphellip凯福隆helliphellip正确的给药方式应该是helliphellip头孢拉定helliphellip正确的给药方式应该是helliphellip西力欣helliphellip正确的给药方式应该是helliphellip另外大家也看到:BID并不代表QH有时护士只是中间间隔一瓶补液就算是BID了。TID也不代表QH。造成这个结果的最主要原因:医护人员对各种药物特性及规范用药的重要性认知不足。但是如果医生完全规范给药实际上有阻力:造成护士的工作量增加门急诊的病人顺应性差一天一剂使用的药物体现出方便有效经济的优越性。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】不规范的给药方式给临床带来的危害DepofEmergencyMedicine【粉乖留爪】*PUMCHospitalDepofEmergencyMedicine【粉乖留爪】临床不规范的给药方式将导致药物浓度长时间低于细菌MIC值细菌不能彻底清除可能有助于耐药细菌的产生CraigWAetal,PediatrInfectJCraigWARespirMed,SupplA:SdiscussionSDepofEmergencyMedicine【粉乖留爪】*照读幻灯片PUMCHospitalDepofEmergencyMedicine【粉乖留爪】DepofEmergencyMedicine【粉乖留爪】*以喹诺酮为例:横坐标代表治疗天数纵坐标代表细菌维持对该抗生素的敏感性。大家可以看到:如果hAUC:MIC,虽然细菌没有清除随着治疗天数的增加这些细菌对该喹诺酮的敏感性仍保持在以上。如果hAUC:MIC,虽然细菌没有清除但随着治疗天数的增加这些细菌对该喹诺酮的敏感性急剧下降导致临床疗效下降。PUMCHospitalDepofEmergencyMedicine【粉乖留爪】从感染部位彻底清除细菌减少病人个体携带耐药菌数治愈病人减少耐药菌的选择性减少耐药菌的传播抗生素的作用DepofEmergencyMedicine【粉乖留爪】*ProfessorDaganwillendhispresentationbycommentingthatantibioticsshouldtreatthewholepatient,ietheyshouldexertapositiveinfluenceatthesiteofinfectionandontheflorainthenasopharynx抗生素的作用包括二个方面:最主要的是从感染部位彻底清除细菌临床治疗病人同时减少耐药菌产生。另一方面每个个体都不同程度携带菌株有些是耐药菌株。运用抗生素后能够减少耐药菌传播PUMCHospitalDepofEmergencyMedicine【粉乖留爪】细菌学治愈:临床治愈临床感染的症状与体症迅速消退防止耐药菌的传播细菌学清除规范的给药方式意味着足够的抗生素治疗规范的给药方式足量抗生素治疗的结果敏感菌耐药菌DaganetalPediatrInfectDisJ:ndashTMICDepofEmergencyMedicine【粉乖留爪】*ProfessorDaganwillendhispresentationbycommentingthatantibioticsshouldtreatthewholepatient,ietheyshouldexertapositiveinfluenceatthesiteofinfectionandontheflorainthenasopharynx规范的给药方式意味着足够的抗生素治疗保证TMIC,假如某种细菌感染了宿主黄色的代表MIC值低的敏感菌绿色的

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