頭孢克洛獨(dú)特的免疫學(xué)特性課件

頭孢克洛獨(dú)特的免疫學(xué)特性1可編輯課件PPT抗生素參與機(jī)體免疫反應(yīng)間接效應(yīng)直接效應(yīng)2可編輯課件PPT間接效應(yīng)殺死細(xì)菌改變腸道菌群抗原性防止細(xì)菌毒素效應(yīng)3可編輯課件PPT直接效應(yīng)激活宿主防御機(jī)制(多形核白細(xì)胞)激活巨噬細(xì)胞－吞噬細(xì)胞伸出偽足包圍細(xì)菌并吞入激活調(diào)理作用－激活補(bǔ)體系統(tǒng)，使細(xì)菌易被吞噬并抑制細(xì)菌酶或毒素產(chǎn)生激活趨化作用－使白細(xì)胞向細(xì)菌移動(dòng)4可編輯課件PPT影響生物學(xué)效應(yīng)的抗菌藥對(duì)宿主防御系統(tǒng)無(wú)活性（一般的β內(nèi)酰胺類抗生素）抑制免疫功能（四環(huán)素類）與免疫系統(tǒng)協(xié)同作用（大環(huán)內(nèi)酯類、喹諾酮類）增強(qiáng)免疫功能（某些頭孢烯β內(nèi)酰胺類）5可編輯課件PPT影響體外免疫反應(yīng)的抗菌藥無(wú)作用作用減弱作用增強(qiáng)多數(shù)β內(nèi)酰胺類某些β內(nèi)酰胺類某些β內(nèi)酰胺類多粘菌素大環(huán)內(nèi)酯類*大環(huán)內(nèi)酯類**糖肽類氨基糖苷類四環(huán)素類氯霉素利福平氯法齊明氯法齊明異煙肼氨苯砜某些喹諾酮類某些喹諾酮類磺胺類夫西地酸克霉唑克霉唑**：體外活組織和體內(nèi)顯示出此活性。**：與所用方法有關(guān)6可編輯課件PPT增強(qiáng)吞噬細(xì)胞功能的β內(nèi)酰胺類頭孢咪唑誘導(dǎo)巨噬細(xì)胞釋放中性粒細(xì)胞刺激因子頭孢克洛恢復(fù)免疫缺陷動(dòng)物模型和人淋巴細(xì)胞的趨化和氧化電勢(shì)頭孢噻肟預(yù)先激活中性粒細(xì)胞對(duì)補(bǔ)體調(diào)理顆粒的反應(yīng)頭孢他啶強(qiáng)化殺菌功能，刺激NK細(xì)胞，增強(qiáng)免疫缺陷的實(shí)驗(yàn)室動(dòng)物模型和病人的趨化和氧化電勢(shì)7可編輯課件PPT文獻(xiàn)報(bào)道?？虅诋?dāng)體外試驗(yàn)敏感，臨床和細(xì)菌學(xué)的療效為95%當(dāng)體外藥敏耐藥，臨床療效為84%。8可編輯課件PPTLeuenbergerP,VrantchevS,Cefactorversusamoxicillininthetreatmentofbacterialpneumonia:acomparativedouble-blindstudy.EurJClinMicrobiology.1983;2(11):11-6.ZeluffB,CatchpoleM,LoweP,etal.Cefadroxilcomparedwithcefaclorinthetreatmentofstreptococcalpneumoniainadults.Drugs.1986;32Suppl;3:39-42.SchleupnerCJ,AnthonyWC,TanJ,etal.Blindedcomparisonofcefuroximetocefaclorforlowerrespiratorytractinfections.ArchinternMed.1988;148(2):343-42.OberlinJA.HyslopDL,Cefaclortreatmentofupperand;owerrespiratorytractinfectionscausedbymoraxellacatarrhalis.PediatrinfectDISJ,1990;9(1):41-4.WettengelR,VetterN,WaardenburgFA.Clarithromycirversuscefaclorforthetreatmentofmild-to-moderateacutebacterialbronchitis.JAntimicrobChemother.1993;31:963-72.O’DohertyB.Anopencomparativestudyofazithromycinversuscefaclorinthetreatmentofpatientswithupperrespiratorytractinfections.JAntimicrobChemother1996;37(SupplC):71-81.TurikMA,JohnsDJr,Comparisonofcefaclorandcefuroximeaxetilinthetreatmentofacuteotitismediawitheffusioninchildrenwhofailedamoxicillintherapy.JChemother,1998;10(4):306-12.HaczynskiJ,BardadinJ,GryczynskaD,etal.Acomparativestudyofcefaclorvs.amoxicillin/clavulanateintonsillopharyngitis.MedSciMonitor.2001;7(5):1016-22.EspositoS,MarchisioP,BososS,etal.Comparativeefficacyandsafetyof5-daycefaclorand10-dayamoxicillinteeatmentofgroupAstreptococcalpharyngitisinchildren.IntJAntimicrobialAgents.2002;20(1)28-33.HaczynskiJ,ChmielikM,BienSetal.Acomparativestudyofcefaclorvs.Amoxicillin/clavulanateinpediatricpharyngotonsillitis.MedSciMonit.2003;9(3):P129-35.CataniaS,GalloA.Clinicalefficacyandtolerabilityofshortcoursetherapywithcefaclorcomparedwithlong-termtherapyfortreatmentofacuteotitismediainchildren.InfezMed.2004;12(4):259-65.AggarwalM,SinhaR,MuraliMV,etal.Comparativeefficacyandsafetyevaluationofcefaclorvsamoxycillin+clavulanateinchildrenwithAcuteOtitisMedia(AOM).IndianJPediatr.2005;72(3):233-8.

希刻勞治療社區(qū)呼吸道感染

臨床療效值得信賴94％

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臨床有效率％9可編輯課件PPT為什么體外藥敏部分細(xì)菌對(duì)?？虅诓幻舾?，但治療后的臨床療效卻很好？10可編輯課件PPT頭孢克洛的免疫調(diào)節(jié)作用體外研究11可編輯課件PPT希刻勞具有體內(nèi)增效抗菌特性Ref:JChemother,1998;10(2):91-96.在人體內(nèi),?？虅谂c中性白細(xì)胞的相互作用,使?？虅诳咕钚燥@著加強(qiáng)（

對(duì)于肺炎鏈球菌的MBC僅為原來(lái)1/8）加入中性粒細(xì)胞前加入中性粒細(xì)胞后MBC降低到1/812可編輯課件PPT頭孢克洛對(duì)金葡菌體內(nèi)外療效比較(第一組)細(xì)菌名稱MICmg/lMBCmg/l加人白細(xì)胞后MBCmg/l金葡2010326416金葡213016648金葡200832648金葡21328164金葡100916328金葡00988164?？虅诰哂畜w內(nèi)增效抗菌特性13可編輯課件PPT頭孢克羅對(duì)金葡菌體內(nèi)及體外療效比較(第二組)細(xì)菌名稱MICmg/lMBCmg/l加白細(xì)胞后MBCmg/l金葡122116644金葡098832648金葡102316328金葡6288324金葡7614162金葡18188648ATCC292134162ATCC49619484?？虅诰哂畜w內(nèi)增效抗菌特性14可編輯課件PPT

?？虅隗w內(nèi)療效明顯大于體外藥敏試驗(yàn)實(shí)驗(yàn)表明：?？虅趯?duì)革蘭氏陽(yáng)性菌體外的MBC要明顯大于體內(nèi)◆頭孢克洛可增強(qiáng)吞噬細(xì)胞的趨化及氧化作用。◆頭孢克洛可抑制白細(xì)胞合成丙三烯，抑制氧自由基形成和組胺釋放。艾效曼,趙瑩,張秀珍.頭孢克洛免疫調(diào)節(jié)功能體外實(shí)驗(yàn)15可編輯課件PPT頭孢克洛對(duì)流感嗜血桿菌體內(nèi)和體外模擬試驗(yàn)編號(hào)MIC/MIC(加免疫細(xì)胞后)MBC/MBC(加免疫細(xì)胞后)10.06/<0.030.125/<0.0320.06/<0.030.125/<0.033<=0.03/<0.03<=0.03/<0.034<=0.03/<0.030.06/<0.035<=0.03/<0.030.06/<0.036<=0.03/<0.030.06/<0.0372/0.58/284/116/292/0.58/2102/0.58/2111/0.54/1121/0.54/2131/0.1254/0.25140.5/0.52/1154/116/2希刻勞具有體內(nèi)增效抗菌特性16可編輯課件PPT頭孢克洛對(duì)卡他莫拉菌菌體內(nèi)和體外模擬試驗(yàn)編號(hào)MIC/加免疫細(xì)胞后MICMBC/加免疫細(xì)胞后MIC1>256/16>256/3228/432/1638/432/848/432/8516/264/1668/216/874/432/884/232/498/432/8108/416/8?？虅诰哂畜w內(nèi)增效抗菌特性17可編輯課件PPT實(shí)驗(yàn)表明：希刻勞對(duì)革蘭氏陰性菌體外的MBC要明顯大于體內(nèi)◆頭孢克洛可增強(qiáng)吞噬細(xì)胞的趨化及氧化作用?！纛^孢克洛可抑制白細(xì)胞合成丙三烯，抑制氧自由基形成和組胺釋放。艾效曼，胡云建，張秀珍修改.頭孢克洛對(duì)流感嗜血桿菌和卡他莫拉菌體內(nèi)模擬實(shí)驗(yàn)

?？虅隗w內(nèi)療效明顯大于體外藥敏試驗(yàn)18可編輯課件PPT頭孢克洛體內(nèi)模擬試驗(yàn)MBC值比較ug/ml細(xì)菌名稱MBC50/加免疫細(xì)胞后MBC50MBC90/加免疫細(xì)胞后MBC90流感嗜血桿菌2/0.125降8倍8/0.5降16倍卡他莫拉菌32/8降4倍64/16降4倍

?？虅隗w內(nèi)療效明顯大于體外藥敏試驗(yàn)19可編輯課件PPT頭孢克洛對(duì)細(xì)胞因子的免疫調(diào)節(jié)作用體內(nèi)研究20可編輯課件PPT感染引起的全身炎癥反應(yīng)及隨后機(jī)體的代償性抗炎癥反應(yīng)是導(dǎo)致臟器功能損傷的主要原因SergioZanotti,SseemKumar,AnandKumar,Cytokinemodulationinsepsisandsepticshock.ExpertOpinInvestig.Drugs2002,11(8):1061-107521可編輯課件PPT細(xì)菌感染治療結(jié)果的決定因素藥物的抗菌作用宿主的免疫功能+通過(guò)體外藥敏試驗(yàn)來(lái)判斷通過(guò)免疫功能測(cè)定先天免疫獲得性免疫M(jìn)anganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

22可編輯課件PPT有些抗菌藥具有免疫調(diào)節(jié)作用抗生素對(duì)宿主先天免疫和獲得性免疫的作用可能影響治療結(jié)果頭孢地嗪免疫調(diào)節(jié)作用最大頭孢噻肟有免疫抑制作用頭孢克洛也具有免疫調(diào)節(jié)作用體外增強(qiáng)粒細(xì)胞的吞噬作用和殺菌活性體外增強(qiáng)巨噬細(xì)胞的吞噬作用和殺菌活性體外增強(qiáng)多形核中性粒細(xì)胞(PMN)的活性可能對(duì)免疫細(xì)胞因子也有調(diào)節(jié)作用23可編輯課件PPT免疫指數(shù)定義免疫指數(shù)=正面報(bào)告數(shù)-負(fù)面報(bào)告數(shù)總的報(bào)告數(shù)24可編輯課件PPT頭孢克洛的免疫調(diào)節(jié)作用可影響機(jī)體免疫防御機(jī)制?？虅诒蛔C實(shí)有提高機(jī)體免疫反應(yīng)的作用◆抗生素能提高機(jī)體的細(xì)胞免疫和體液免疫。◆抗生素能降低細(xì)菌的毒力因子或使其更易被免疫攻擊。◆抗生素能幫助機(jī)體免疫功能的恢復(fù)。1、JM.T.HAMILTON-MILLERDepartmentofMedicalMicrobiology,RoyalFreeandUniversityCollegeMedicalSchool.London,U.K.ImmunopharmacologyofAntibiotics:DirectandIndirectImmunomodulationofDefenceMechanismsLEADINGARTICLEJournalofchemotherapyVol2001;13(2):107-11125可編輯課件PPT頭孢克洛對(duì)免疫的調(diào)節(jié)作用動(dòng)物試驗(yàn)ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

26可編輯課件PPT細(xì)胞因子與免疫功能I型細(xì)胞因子：促炎癥細(xì)胞因子IFN-γ、TNF-α、IL-1、IL-2、IL-12、IL-18刺激細(xì)胞介導(dǎo)的免疫效應(yīng)細(xì)胞，如巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞上調(diào)遲發(fā)型超敏反應(yīng)調(diào)節(jié)免疫，參與清除胞內(nèi)病原體2型細(xì)胞因子IL-4、IL-5、IL-6、IL-10、IL-13主要調(diào)節(jié)體液免疫應(yīng)答，刺激IgG1和IgE的生成下調(diào)巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞的功能活性3型細(xì)胞因子TGF-β主要調(diào)節(jié)體液免疫應(yīng)答，刺激IgG1和IgE的生成下調(diào)巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞的功能活性27可編輯課件PPT實(shí)驗(yàn)方法大鼠口服頭孢克洛劑量是10、50或100mg/kg/d療程3天或6天對(duì)照組口服磷酸鹽緩沖液(PBS)吸入CO2處死動(dòng)物取動(dòng)物脾臟，制備細(xì)胞懸液進(jìn)行免疫試驗(yàn)淋巴細(xì)胞增殖試驗(yàn)測(cè)定各種細(xì)胞因子水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

28可編輯課件PPT主要結(jié)果29可編輯課件PPT頭孢克洛刺激淋巴細(xì)胞增殖ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

細(xì)胞增殖指數(shù)P=0.001P=0.001P=0.002P=0.045*P值是與頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果P=0.00230可編輯課件PPT頭孢克洛刺激淋巴細(xì)胞增殖ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

細(xì)胞增殖指數(shù)P<0.001P<0.001P<0.001P=0.001P=0.001P=0.004*P值是與頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果31可編輯課件PPT頭孢克洛刺激TNF-α的合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml32可編輯課件PPT頭孢克洛刺激TNF-α的合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml33可編輯課件PPT頭孢克洛刺激IFN-γ的合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P≤0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果**34可編輯課件PPT頭孢克洛刺激IFN-γ的合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P≤0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果*35可編輯課件PPT頭孢克洛刺激IL-2的合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P=0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果*36可編輯課件PPT頭孢克洛刺激IL-2的合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P≤0.001，**p=0.007，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果***37可編輯課件PPT頭孢克洛降低IL-4水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P≤0.001，**p=0.003，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果****38可編輯課件PPT頭孢克洛降低IL-4水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P≤0.001，**p=0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果****39可編輯課件PPT頭孢克洛降低IL-6水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml40可編輯課件PPT頭孢克洛降低IL-6水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647

pg/ml*P≤0.001，**p=0.008，***p=0.014，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果******41