頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座

抗生素參加機(jī)體免疫反應(yīng)間接效應(yīng)直接效應(yīng)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第1頁(yè)間接效應(yīng)殺死細(xì)菌改變腸道菌群抗原性預(yù)防細(xì)菌毒素效應(yīng)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第2頁(yè)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)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第3頁(yè)影響生物學(xué)效應(yīng)抗菌藥對(duì)宿主防御系統(tǒng)無(wú)活性（普通β內(nèi)酰胺類(lèi)抗生素）抑制免疫功效（四環(huán)素類(lèi)）與免疫系統(tǒng)協(xié)同作用（大環(huán)內(nèi)酯類(lèi)、喹諾酮類(lèi)）增強(qiáng)免疫功效（一些頭孢烯β內(nèi)酰胺類(lèi)）頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第4頁(yè)影響體外免疫反應(yīng)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(lèi)一些β內(nèi)酰胺類(lèi)一些β內(nèi)酰胺類(lèi)多粘菌素大環(huán)內(nèi)酯類(lèi)*大環(huán)內(nèi)酯類(lèi)**糖肽類(lèi)氨基糖苷類(lèi)四環(huán)素類(lèi)氯霉素利福平氯法齊明氯法齊明異煙肼氨苯砜一些喹諾酮類(lèi)一些喹諾酮類(lèi)磺胺類(lèi)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。**：與所用方法相關(guān)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第5頁(yè)增強(qiáng)吞噬細(xì)胞功效β內(nèi)酰胺類(lèi)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)免疫缺點(diǎn)動(dòng)物模型和人淋巴細(xì)胞趨化和氧化電勢(shì)頭孢噻肟預(yù)先激活中性粒細(xì)胞對(duì)補(bǔ)體調(diào)理顆粒反應(yīng)頭孢他啶強(qiáng)化殺菌功效，刺激NK細(xì)胞，增強(qiáng)免疫缺點(diǎn)試驗(yàn)室動(dòng)物模型和病人趨化和氧化電勢(shì)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第6頁(yè)文件報(bào)道?？虅诋?dāng)體外試驗(yàn)敏感，臨床和細(xì)菌學(xué)療效為95%當(dāng)體外藥敏耐藥，臨床療效為84%。頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第7頁(yè)LeuenbergerP,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.;7(5):1016-22.EspositoS,MarchisioP,BososS,etal.Comparativeefficacyandsafetyof5-daycefaclorand10-dayamoxicillinteeatmentofgroupAstreptococcalpharyngitisinchildren.IntJAntimicrobialAgents.;20(1)28-33.HaczynskiJ,ChmielikM,BienSetal.Acomparativestudyofcefaclorvs.Amoxicillin/clavulanateinpediatricpharyngotonsillitis.MedSciMonit.;9(3):P129-35.CataniaS,GalloA.Clinicalefficacyandtolerabilityofshortcoursetherapywithcefaclorcomparedwithlong-termtherapyfortreatmentofacuteotitismediainchildren.InfezMed.;12(4):259-65.AggarwalM,SinhaR,MuraliMV,etal.Comparativeefficacyandsafetyevaluationofcefaclorvsamoxycillin+clavulanateinchildrenwithAcuteOtitisMedia(AOM).IndianJPediatr.;72(3):233-8.

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臨床療效值得信賴(lài)94％

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臨床有效率％頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第8頁(yè)為何體外藥敏部分細(xì)菌對(duì)?？虅诓幻舾?，但治療后臨床療效卻很好？頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第9頁(yè)頭孢克洛免疫調(diào)整作用體外研究頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第10頁(yè)?？虅诤畜w內(nèi)增效抗菌特征Ref:JChemother,1998;10(2):91-96.在人體內(nèi),?？虅谂c中性白細(xì)胞相互作用,使?？虅诳咕钚燥@著加強(qiáng)（

對(duì)于肺炎鏈球菌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1/8頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第11頁(yè)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(chēng)MICmg/lMBCmg/l加人白細(xì)胞后MBCmg/l金葡326416金葡213016648金葡32648金葡21328164金葡100916328金葡00988164?？虅诤畜w內(nèi)增效抗菌特征頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第12頁(yè)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(chēng)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?？虅诤畜w內(nèi)增效抗菌特征頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第13頁(yè)

?？虅隗w內(nèi)療效顯著大于體外藥敏試驗(yàn)試驗(yàn)表明：?？虅趯?duì)革蘭氏陽(yáng)性菌體外MBC要顯著大于體內(nèi)◆頭孢克洛可增強(qiáng)吞噬細(xì)胞趨化及氧化作用?！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,趙瑩,張秀珍.頭孢克洛免疫調(diào)整功效體外試驗(yàn)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第14頁(yè)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?？虅诤畜w內(nèi)增效抗菌特征頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第15頁(yè)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?？虅诤畜w內(nèi)增效抗菌特征頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第16頁(yè)試驗(yàn)表明：?？虅趯?duì)革蘭氏陰性菌體外MBC要顯著大于體內(nèi)◆頭孢克洛可增強(qiáng)吞噬細(xì)胞趨化及氧化作用?！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)模擬試驗(yàn)

?？虅隗w內(nèi)療效顯著大于體外藥敏試驗(yàn)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第17頁(yè)頭孢克洛體內(nèi)模擬試驗(yàn)MBC值比較ug/ml細(xì)菌名稱(chēng)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)療效顯著大于體外藥敏試驗(yàn)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第18頁(yè)頭孢克洛對(duì)細(xì)胞因子免疫調(diào)整作用體內(nèi)研究頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第19頁(yè)感染引發(fā)全身炎癥反應(yīng)及隨即機(jī)體代償性抗炎癥反應(yīng)是造成臟器功效損傷主要原因SergioZanotti,SseemKumar,AnandKumar,Cytokinemodulationinsepsisandsepticshock.ExpertOpinInvestig.Drugs,11(8):1061-1075頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第20頁(yè)細(xì)菌感染治療結(jié)果決定原因藥品抗菌作用宿主免疫功效+經(jīng)過(guò)體外藥敏試驗(yàn)來(lái)判斷經(jīng)過(guò)免疫功效測(cè)定先天免疫取得性免疫M(jìn)anganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,18(6):641-647

頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第21頁(yè)有些抗菌藥含有免疫調(diào)整作用抗生素對(duì)宿主先天免疫和取得性免疫作用可能影響治療結(jié)果頭孢地嗪免疫調(diào)整作用最大頭孢噻肟有免疫抑制作用頭孢克洛也含有免疫調(diào)整作用體外增強(qiáng)粒細(xì)胞吞噬作用和殺菌活性體外增強(qiáng)巨噬細(xì)胞吞噬作用和殺菌活性體外增強(qiáng)多形核中性粒細(xì)胞(PMN)活性可能對(duì)免疫細(xì)胞因子也有調(diào)整作用頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第22頁(yè)免疫指數(shù)定義免疫指數(shù)=正面匯報(bào)數(shù)-負(fù)面匯報(bào)數(shù)總匯報(bào)數(shù)頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第23頁(yè)頭孢克洛免疫調(diào)整作用可影響機(jī)體免疫防御機(jī)制?？虅诒蛔C實(shí)有提升機(jī)體免疫反應(yīng)作用◆抗生素能提升機(jī)體細(xì)胞免疫和體液免疫?！艨股啬芙档图?xì)菌毒力因子或使其更易被免疫攻擊?！艨股啬軒椭鷻C(jī)體免疫功效恢復(fù)。1、JM.T.HAMILTON-MILLERDepartmentofMedicalMicrobiology,RoyalFreeandUniversityCollegeMedicalSchool.London,U.K.ImmunopharmacologyofAntibiotics:DirectandIndirectImmunomodulationofDefenceMechanismsLEADINGARTICLEJournalofchemotherapyVol;13(2):107-111頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第24頁(yè)頭孢克洛對(duì)免疫調(diào)整作用動(dòng)物試驗(yàn)ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,18(6):641-647

頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第25頁(yè)細(xì)胞因子與免疫功效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)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)整免疫，參加去除胞內(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)整體液免疫應(yīng)答，刺激IgG1和IgE生成下調(diào)巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞功效活性3型細(xì)胞因子TGF-β主要調(diào)整體液免疫應(yīng)答，刺激IgG1和IgE生成下調(diào)巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞功效活性頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第26頁(yè)試驗(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.JournalofChemotherapy,18(6):641-647

頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第27頁(yè)主要結(jié)果頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第28頁(yè)頭孢克洛刺激淋巴細(xì)胞增殖ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果P=0.002頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第29頁(yè)頭孢克洛刺激淋巴細(xì)胞增殖ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第30頁(yè)頭孢克洛刺激TNF-α合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,18(6):641-647

pg/ml頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第31頁(yè)頭孢克洛刺激TNF-α合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,18(6):641-647

pg/ml頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第32頁(yè)頭孢克洛刺激IFN-γ合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果**頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第33頁(yè)頭孢克洛刺激IFN-γ合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果*頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第34頁(yè)頭孢克洛刺激IL-2合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果*頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第35頁(yè)頭孢克洛刺激IL-2合成ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果***頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第36頁(yè)頭孢克洛降低IL-4水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果****頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第37頁(yè)頭孢克洛降低IL-4水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,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)結(jié)果****頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第38頁(yè)頭孢克洛降低IL-6水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,18(6):641-647

pg/ml頭孢克洛獨(dú)特的免疫學(xué)特性專(zhuān)家講座第39頁(yè)頭孢克洛降低IL-6水平ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy,18(6):641-647

pg/ml*P≤0.001，**p=0.008，***p=0.014，頭孢克洛組與賦形劑