抗生素临床应用

抗菌药物临床应用肖永红北京大学第一医院抗生素细菌人体RESISTANCEBACTERICIDEINFECTIONIMMUNITYSIDEEFFECTSPHARMACOKINETICS抗生素选择时需考虑的因素药物感染部位浓度对细菌MIC结果微生物学抗菌机制抗菌谱耐药性药代动力学吸收、分布、代谢、排泄给药方案药效学时间/浓度依赖型杀菌剂/抑菌剂组织渗透抗菌时效临床效果细菌清除患者依从性耐受性时效价格抗菌药物临床应用抗菌药物基础知识各类抗菌药物特点β-内酰胺类抗菌药物喹诺酮类药物抗阳性菌药物抗生素药代动力学药效学毒理学特殊抗生素应用细菌耐药机制特别细菌感染（人体）抗生素应用基础理论抗生素抗菌作用机制抗生素药效学细菌敏感性(MIC/MBC)抗菌谱(抗菌机制)抗菌特征（杀菌/抑菌）抗生素后效应(PAE)抗生素联合MIC/MBCMIC:体外培养基中孵育18-24小时后，能抑制细菌生长的最低抗生素浓度。MBC:体外培养基中孵育18-24小时后，能杀灭99.9%细菌的最低抗生素浓度。抗生素针对菌万古霉素氟喹诺酮类谱（SPECTRUM）

不同类别抗生素联合效应

1.抗菌效果分类：

杀菌剂：ß-内酰胺,氨基甙类，喹诺酮类

抑菌剂：四环素,磺胺,林可酰胺类,大环内酯类

2.联合效应一般原则

杀菌剂+杀菌剂：协同

杀菌剂+抑菌剂：拮抗

联合用药的优点

1.取得协同抗菌作用

磺胺+TMP

青霉素+氨基甙类

两性霉素B+氟胞密啶

2.处理混合性感染

3.减少耐药菌产生

4.严重感染的经验治疗

联合用药的缺点

1.可能的拮抗作用

2.增加毒副反应

3.增加费用

4.不恰当使用可能增加耐药菌产生

药代动力学（Pharmacokinetics）CmaxCluVdTmaxA、ßT1/2、AUCC=Ae-at-Be-bt抗生素药代动力学参数：T1/2CmaxSiteconcentrationsExcretion抗生素药代动力学特殊人群：老人儿童肾功不良者肝功不良者孕妇哺乳期药代鲜动力简学vs药效学Cm互ax/M跪ICAU替C/走MI裙C不同膨药物继不同若浓度扶杀菌蚁曲线Ti亲me烦（h蛮）Lo籍gC翠FUTo坡br塔am辆yc敢inCi张pr简of蜡lo假xa美ci巾nTi餐ca娇rc记il仆li隔n抗生罩素PK门/P增D参数T(缴h)Co扇n.Cm船ax/M存ICAU映C/出MI屿CMI倦CT>亭MI喘C浓度犹依赖检性抗膊生素扮（AU垂C/锐MI枝C）AU抚C/叫MI取CEf千fe锈ct傲iv粘e桃ra党te订s1.抗生火素的桥抗菌再活性谷随药叹物浓码度淹增仅加而撞增加;匪2.临床隆用药恩目的窝：取它得抗布生素Cm极ax/M样IC嗽>乐10倡;去3绝.这类虚药物煎有：兴氨基阴甙类贴、喹励诺嚼酮衔类、顾阿奇牧霉素扰、四再环素谊、链肠阳霉科素、敬万古辫霉素卫。浓度鸡依赖绣性抗趟菌作毁用T>MIC(%)Bacterialeradicationday4-6oftherapy(%)204060801000204060801000PSSPPISP-PRSPH.influenzae浓度害非依极赖性移抗生扭素（T>肚MI键C）浓度蹲非依锋赖性尾抗菌益作用抗生化素的限抗菌疑作用霸与药闯物浓铅度关童系不杆密切严，而注与抗苗生素拢浓度耍维持盖在细沫菌MI炊C之上孝有关;临床吩用药沈目的丝式在于逆维持鼻药物主浓度侍在细段菌MI羞C之上评一定延时间雾。一洞般为40愤%给药议间歇苍以上;这类脾药物风有：ß-内酰郑胺类尘、红烘霉素扔、克付拉霉欧素、岂可林抬霉素把、恶睡唑烷设酮.抗生膛素药匠效学折与药烛代动裳力学贷分类抗生素类别PK/PD参数药物时间依赖性（短PAE）T>MIC青霉素类、头孢菌素类、氨曲南、碳青霉烯类、大环内酯类、克林霉素、恶唑烷酮类、氟胞嘧啶时间依赖性（长PAE）AUC24/MIC链阳霉素、四环素、万古霉素、替考拉林、氟康唑、阿齐霉素浓度依赖性AUC24/MIC或Cmax/MIC氨基糖苷类、氟喹诺酮类、daptomycin、酮内酯、甲硝唑、两性霉素B%T安>M石IC桶=ln凶[D扭os睛e/俊(V托d×MI要C)]×T称1/袄2/的ln米2×10刮0/壮DI抗菌贺药物俩临床舰应用抗菌炸药物困基础虫知识各类羽抗菌滥药物押特点β-内酰顶胺类遥抗菌胆药物喹诺栗酮类仰药物抗阳吃性菌降药物ß-内酰加胺抗朗生素SU浆LB领AC笼TA蹦MIM乏IP凭EN逼EMAM染PI篇CI碗LL韵INCE果FO角TA遍XI纽奉MECA俯RU督MO禽NA坐MLA脊TA肿MO搭XE形FLI皆TI肆PE抓NE柿MLO桃RA间CA长RB练IF细菌斩细胞宏壁粘弟肽结伏构青霉话素G青霉贷素V氨苄垦西林苯唑拖西林哌拉卷西林头孢掀菌素摸分代分代通（组昂）原芹则化学伴结构药理魄学特言征开发范年代注射邻用头享孢菌蜘素口服攀用头萌孢菌刑素00sCeftobiprole、cefotaroline5th1990s头孢吡肟、头孢匹罗、头孢噻利、头孢唑兰、头孢喹肟、头孢瑞南4thG1980s头孢噻肟、头孢甲肟、头孢唑肟、头孢曲松、头孢他定、头孢哌酮、头孢磺啶、头孢匹胺、头孢米唑、头孢地嗪、头孢替胺3rdG头孢克肟、头孢布烯、头孢地尼、头孢他美酯、头孢泊肟酯、头孢特伦酯、头孢妥仑酯、头孢卡品酯、头孢替胺酯70-80s头孢呋辛、头孢唑南、头孢尼西、头孢替坦、头孢西丁、头孢美唑、头孢羟唑、头孢拉宗、头孢米诺2ndG头孢呋辛酯、头孢克罗头孢丙烯、氯碳头孢1960s头孢噻吩、头孢噻定、头孢曲嗪、头孢乙嗪、头孢氮氟、头孢替唑、头孢西酮、头孢唑啉、头孢拉定、头孢硫眯IstG头孢氨苄、头孢羟氨苄、头孢拉定头孢案菌素弄的发叶展酯化头孢截菌素伪构效惩关系抗菌表活性药代甚特征药代识特征对酶喝稳定叶性抗菌糠活性分类C7位特征C3位特征药品第一代头孢菌素肠外、酶不稳定，快代谢无特别，对没不稳定乙酰甲基，快速代谢，短半衰期头孢噻吩肠外，酶不稳定，代谢稳定无特别，对没不稳定其他基团取代乙酰甲基，代谢稳定头孢唑林口服，酶不稳定，代谢稳定酰基侧链其他基团取代乙酰甲基，代谢稳定CH3头孢氨苄第二代头孢菌素肠外，酶稳定，代谢稳定酰基侧链，对酶稳定，抗菌谱扩大到产头孢酶细菌其他基团取代乙酰甲基头孢孟多头霉素甲氧基头孢美唑头孢屋菌素轧的SA轧R分类C7位特征C3位特征药品第三代头孢菌素肠外，耐酶，代谢稳定肟基不同头孢噻肟口服，酶稳定，代谢稳定肟基不同头孢布烯口服，酶稳定，代谢稳定肟基C4脂头孢泊肟第四代头孢菌素肠外，耐酶，代谢稳定肟基4价氮头孢吡肟头孢派菌素俘的SA德R各代撞头孢描菌素肢大致传比较代别G+MRSAG-非发酵普通酶ESBLs安全性适应症1st+++-±/+-±-++2nd

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+/++-+++-/+++-++++4th

++-+++++++-++++5th

++++++++++-？+近年菜来头俘孢菌福素发络展情啄况给药方式分代药品名称商品名开发公司上市年代首市国家注射用五代ceftobiproleJ&J2009USA五代ceftarolineAZ-PhaseII四代cefopiromeCefromHoechst1992Sweden四代cefepimeMaxipimeBMS1993Sweden四代cefozopranFirstcinTaketa1995Japan四代cefoselisWincefFujisawa1998Japan三代cefodizimeNeucefHoechst1990Japan口服三代cefdinirCefzonFujisawa1991Japan三代ceftibudinCedaxShionoge1993Japan三代cefpodoximeBananSankyo1990Japan三代cefetametGlobcefTaketa1992Mexico三代cefditorenMeiactMeiji1994Japan三代cefcapeneFlomoxShionoge1997Japan二代cefotiamPansporinTaketa1991Japan二代cefprozilCefzilBMS1992US二代loracarbefLorabidKyowa1992US头孢堂菌素巧体外崭抗菌念活性亡比较（MI捐C9改0,拒m棋g/矛L）细菌头孢吡肟头孢匹罗头孢噻利头孢克啶头孢噻肟头孢他啶MSSA3.13/500.78/6.256.25/12.512.5/50MSSE0.78/250.39/6.253.13/12.56.25/50化脓链球菌0.0150.008<0.0080.060.0080.25无乳链球菌0.250.006<0.060.50.060.5头孢升菌素仔体外夕抗菌从活性耻比较个（MI仰C9围0,掉m苦g/歌L）细菌头孢吡肟头孢匹罗头孢噻利头孢克啶头孢噻肟头孢他啶肺炎链球菌0.50.015<0.0080.50.0150.5粪肠球菌6432>32>32>128>128屎肠球菌>16>128>32>128>128鸟肠球菌>100>100>100>100>100>100头孢威菌素六体外即抗菌惑活性胞比较禾（MI光C9弃0,首m俭g/贷L）细菌头孢吡肟头孢匹罗头孢噻利头孢克啶头孢噻肟头孢他啶大肠杆菌0.060.060.060.10.120.5肺炎杆菌0.060.060.120.20.060.5变形杆菌0.060.12<0.060.390.030.12枸橼酸菌4143.133264头孢声菌素沿体外膨抗菌帐活性阀比较棍（MI坊C9警0,宗m孙g/验L）细菌头孢吡肟头孢匹罗头孢噻利头孢克啶头孢噻肟头孢他啶产气杆菌0.50.1210.248阴沟杆菌4243.136464沙雷菌10.250.50.3941莫根菌0.030.060.120.221头孢烫菌素亲体外洗抗菌丛活性雄比较姐（MI泳C9蛛0,史m臭g/禾L）细菌头孢吡肟头孢匹罗头孢噻利头孢克啶头孢噻肟头孢他啶绿脓杆菌3.136.2580.78>323.13窄食单胞菌16128>32>32128128不动杆菌1005010050流感杆菌0.060.120.250.390.060.25碳青产霉烯雅类药挂物发盖展介线绍Th嫂ie扶na古my随ci藏n19挺78Im唇ip糖en饼em19袍87Pa迁ni秒pe栏ne喂m19饶93Me床ro旅pe尚ne邪m19烛95Bi从ap么en解em20业02Er探ta董pe对ne肠m20评02药物仁发展饭介绍碳青睁霉烯生类广铺谱、泄强效师的原蹦因对β-内酰速胺酶孙稳定珠（抑谎酶）PD、PK影响对DP玩H-婶I稳定碳青透霉烯隆类体痛外抗玩菌活蓝性比垦较AntibioticsS.aureus(30),MSSAS.epidermidis(46),MSSEMICrMIC50MIC90MICrMIC50MIC90Imipenem0.016-0.1250.0320.0320.008-0.0320.0160.016Meropenem0.063-0.1250.1250.1250.0630.1250.125Biapenem0.063-0.1250.1250.1250.032-0.1250.0630.125Cefpirome0.25-1110.125-10.50.5Ceftazidime8-1616164-1688AA紫C,墨19全98训,4师2:浮94滩-9店9碳青伸霉烯狠类体派外抗厌菌活边性比愚较AntibioticsS.pyogenes(42)S.pneumoniae(25),PRSPMICrMIC50MIC90MICrMIC50MIC90Imipenem<0.004-0.008<0.0040.0080.008-20.250.25Meropenem<0.004-0.0080.0080.0080.016-20.250.5Biapenem<0.004-0.010.0080.0080.016-40.250.5Cefpirome0.008-0.0160.0080.0080.032-20.50.5Ceftazidime0.125-0.250.1250.250.125-32832AA弦C,与19率98次,4象2:脏94开-9征9碳青赏霉烯闯类体膀外抗起菌活热性比吧较AntibioticsE.coli(30)K.pneumoniae(30)MICrMIC50MIC90MICrMIC50MIC90Imipenem0.063-0.250.1250.1250.063-0.250.1250.25Meropenem0.016-0.0320.0160.0160.0320.0320.032Biapenem0.032-0.0630.0320.0630.032-0.250.0630.125Cefpirome0.016-0.1250.0320.0630.032-0.1250.0320.063Ceftazidime0.063-10.250.250.063-0.50.1250.25AA关C,渡19惜98造,4窃2:增94安-9觉9碳青纺霉烯参类体位外抗弹菌活涉性比鹿较AntibioticsP.mirabilis(27)C.freundii(22)MICrMIC50MIC90MICrMIC50MIC90Imipenem0.125-0.50.250.50.125-10.250.5Meropenem0.0320.0320.0320.016-0.0630.0320.032Biapenem0.032-10.1250.50.063-10.0630.125Cefpirome0.008-0.1250.0320.0630.016-10.0320.063Ceftazidime0.032-0.50.1250.250.25-1280.51AA翅C,草19量98济,4陵2:神94蚀-9龙9碳青疏霉烯珠类体芳外抗消菌活来性比腰较AntibioticsE.cloacae(30)S.marcescens(30)MICrMIC50MIC90MICrMIC50MIC90Imipenem0.125-10.250.50.25-20.251Meropenem0.016-0.1250.0320.0630.032-80.0630.125Biapenem0.032-0.50.0630.1250.125-80.251Cefpirome0.016-40.06340.032-320.0630.5Ceftazidime0.063->1280.251280.125-1280.1250.5AA嗽C,喝19朝98咳,4叛2:尊94钞-9氏9碳青绘霉烯途类体笋外抗个菌活菌性比霜较AntibioticsP.aeruginosa(83),imi-sensitiveB.cepacia(25)MICrMIC50MIC90MICrMIC50MIC90Imipenem0.25-8188-321632Meropenem0.032-80.2522-848Biapenem0.125-80.544-16816Cefpirome2->12883216->12864128Ceftazidime0.5-1282322-1648AA毙C,丢19扶98畅,4湿2:欧94雄-9亲9BacteriaImiMeroBiaPaniLenaCS-834S-4661MSSA≤0.0080.060.060.030.030.120.06MRSA3216320.1283216MSCoNS<0.0080.060.060.0150.0150.060.03MRCoNS16161614816PSSP≤0.0080.0150.0150.0150.0150.0080.008PRSP0.250.25E.faecium128<128<128128128128E.faecalis1441482C.difficile81811碳青吧霉烯超类体塞外抗越菌活泛性比泉较(M趟IC壁50尝)Cl鞭inPh露ar馆ma砍co胀ki支ne帆t20滚00泊,3庙9:未18伟5BacteriaImiMeroBiaPaniLenaCS-834S-4661H.influenzae10.060.50.50.060.12E.coli0.120.0150.030.060.030.0150.015K.pneumoniae0.120.030.120.120.060.0150.03Proteusspp.20.0620.1220.060.25S.marcescens0.250.060.250.250.250.120.12Enterobacter0.250.030.060.250.030.120.03Acinetobacter0.120.250.120.120.120.5P.aeruginosa10.250.520.5320.25S.maltophilia>12864>128>128>128B.fragilis0.250.120.250.030.250.12碳青腐霉烯砍类体捐外抗山菌活将性比俊较(M舌IC肚50裙)DrugDose(mg)Cmax(mg/L)t½β(h)V(L)Cl(L/h)Pb(%)Imipenem/cilastatin500/50021-580.9-1.1114.4-15.911.0-12.22031-4940Panipenem/betamipron500/50027.51.17±0.3019.8±5.40.28±0.05415.60.71±0.1829.3±9.80.71±0.17Meropenem50021-300.82-1.120.916.69Biapenem50032.4±2.3(600)1.42-3.413.36.66-9.90NALenapenem5001.43±0.1414.04±1.347.86±1.42NACS-8341500.81±0.25NA49.5±12.916-20ertapenem10001554.50.121.895碳青肚霉烯貌类药春代动嘴力学(I胞V)参数袄比较Cl步inPh害ar射ma跪co工ki篇ne挽t20勉00虹,3吼9(嫁3)崇:1膀90疑-1枝98碳青因霉烯核类PK爽/P拾D比较药物给药方案目标T>MICMIC>4mg/LMIC>1mg/LImipenem500mg,qid4578Meropenem1000mg,tid4671panipenem500mg,tid3652Biapenem500mg,tid5088Cl茂inPh劣ar灵ma顽co宫ki冠ne犯t20践00及,3盐9(批3)诱:1幅90每-1墓98BacterialspeciesResistantmechanismsGrampositivecocciTargetmutationEnterobacteriaceaeCephalosporinase+porinlossCarbapenemaseP.aeruginosaPorinlossUp-regulatedeffluxCarbapenemaseAcinetobacterspp.Cephalosporinase+porinlossCarbapenemase细菌碌对碳御青霉少烯类界耐药巾机制细菌添对碳高青霉茫烯类蔽耐药鞋机制分子分类酶型酶解谱抑酶效应产生菌遗传物质氨基青霉素脲基青霉素广谱头孢菌素氨曲南碳青酶烯克拉维酸EDTAANmcA,Sme1-2,IMI1-2+++-++++/--E.Cloacae,M.marcescensChromAKPC1-4++++++++++-K.pneu,EnterobacterPlasmidASHV-38+++++++++-K.pneu.PlasimdAGES1-9++++++++++-P.aeru,K.pneu,E.coliPlasmidIntegronBIMP1-18++++++-++-+Enterobacter,Pseudo,Alcal,AcinetPlasmid,Chrom,IntegronBVIM1-11++++++-++-+P.aeru,P.putides,A.baumPlasmid,Chrom,IntegronDOXA(23-27)+++++-++/--A.baumaniichrom,integron碳青跳霉烯锤酶比名较CM弟I,饰2房诚00群2,央8:只32旷1,滔JA驰C,纱20奋07揪,6蜓0:伪47拜0Ki尾ne逢ti燃c遵Pa漂ra爽me谢te拒rs蛙o倾fCa们rb察ap愿enam池as晕esfo抵rCa告rb点ap警en粉em斤sEnzymeSubstratekcat(s-1)RelativekcatKm(μM)kcat/Km(μM-1s-2)Relativekcat/KmCcrAImipenem1510063240100Meropenem8.4563822092Biapenem3.725200197.9L1Imipenem2.01002676100Meropenem0.88441180110Biapenem0.5528192938Sme-1Imipenem0.33100665.0100Meropenem0.0288.54.36.5130Biapenem0.034105.46.3130IMI-1Imipenem100100170530100Meropenem10102638071Biapenem9.49.43229055AA皮C,姻1即99舌9,录12扎:2险90肾4–狡29株09DrugsIMP-6IMP-1MIC*kmkcatKcat/kmMICKmKcatKcat/kmImipenem2681100.61246391.2Panipenem41802500.71250100.12meropenem64327.64.20.544301.5AA唱C.盖45泡.5这.1提34组3–束13瞒48现.2捆00射1细菌完对碳型青霉种烯类蛛耐药裤机制*MI扒C为大铃肠杆萝菌带im枣p基因怪时MI悔C金属慌碳青箭霉烯也酶比废较细菌菌对碳教青霉磨烯类家耐药复机制A组碳眼青霉融烯酶像比较掀（Kc凑at/K膀m）AntibioticsKPC-1KPC-2KPC-3Ampicillin0.90.91.2Nitrocefin--2.6Cephaloridine0.61.11.4Cephalotin1.40.83.5Cefotaxime0.10.10.5Ceftazidime0.001-0.03Cefoxitin0.0020.0020.5Moxalactam--0.05Meropenem0.30.31.4Imipenem0.20.31.9Sulbactam--0.1AA折C,乡丰20液05光,4库9:练47号60流出器通道(Op遣rM)外膜周质众间隙连接唱脂蛋释白(Me股xA)胞浆储膜流出陵泵系依统(Me姓xB)膜孔攀蛋白(Op略r)主动啄外排揪系统乐结构朵图细菌树对碳错青霉田烯类却耐药菊机制J滑In少fe伤ctCh劈燕em地ot对he见r(2理00截2)茅8稳:3速71必–3蜜73护,端J弦An忠ti睡bi尿ot惧ic回s雀19辆95休;4吃8:后89仿–9算1DrugsOprD2EffluxsystemsMexAB-OprMMexXY-OprMMexCD-OprJImipenem√XXXBiapenem√XXXBO2727√X√XPanipenem√?√XMeropenem√√X√S4665√√√√DU6681√√√√为浓予度非架依赖寇性抗馅生素娘。对革兰换阳性尽菌有顿一定PA录E，对革兰股阴性娱菌没圈有PA须E。T>鹅MI裹C对治疗牛效果着有较慈好预临见作籍用.当药物液浓度底低于MI幻玉C时,细菌袋很快腥恢复放生长.5.半衰巡寿期普蛋遍较市短,需多侮次给趋药.持续铜静脉侧滴注继疗效绸可能询优于迟间歇惹多次好给药.同时蛇药品劝经济联学更痰优.不良假反应悟不一占定与桌恒定鞋血清条或组怕织浓文度有雨关.ß-内酰湿胺类狭药效枣学特拥点喹诺荷酮类氟喹毯诺酮哲类药春物ND讽Aci薪noen置oxno笋rfPP供Aof堵loci茂pr柿oLe喇vope抖flle响mofl衡ersp轨arto史sute韵matr称avcl揪insi虾tage月mipa滴zuba树lopr土ulmo夸xiga独tigr输epga蹦requ雾in洋in樱eru湾fdi泳fam挡i苯吡堂啶奈啶保酮泌尿都感染阴性浮菌感孟染广谱豆药物呼吸吉喹诺捞酮喹诺块酮的证分代国际分代国内分代代表药物代表结构11/2奈啶酸,吡哌酸2a3氟哌酸,环丙沙星,氧氟沙星,左氧沙星2b斯帕沙星,格帕沙星3a4加替沙星,曲伐沙星,莫西沙星3b吉米沙星45garenoxacinAABB喹诺谦酮类杏抗菌延作用龄机制氟喹盯诺酮朴构效万关系DN眼A结合农部位F>渣>HNH绑2>扬OH伞>C忧H3抗菌连活性稿影响Hal钻ky探lG-↑G+↑G+↑抗厌亡氧菌活性↑Ｃl,膨FO-家CH淘3OC悄H2链FO-固CH促3耐药卫选择↓>抬>C码(C零H3倦)2活性衫增强IsolatesCiproOfloLevoMoxiS.pneumoniaeCIP-S1210.25S.pneumoniaeCIP-R6432164H.influenzae0.0160.060.030.06M.catarrhalis0.030.1250.1250.125S.aureusCIP-S0.50.50.250.06S.aureusCIP-R>12832164P.aeruginosaCIP-S0.5428P.aeruginosaCIP-R128>128>128>128M.pneumoniae410.50.125常用稿氟喹验诺酮愉类体扭外抗胡菌活述性(M膀IC寺90广)氟喹山诺酮哀类对E.芦c背ol目i活性花比较E.coli(100)MIC(mg/L)%SusceptibilityRange50%90%Ciprofloxacin≤0.03-0.12≤0.030.03100Moxifloxacin≤0.03-0.250.030.06100Gatifloxacin≤0.03-0.50.060.12100Levofloxacin≤0.03-0.120.030.03100Pip/tazobactam0.12->1280.5490Imipenem≤0.03-0.50.120.25100K.Pneumoniae(40)MIC(mg/L)%susceptibilityRange50%90%Ciprofloxacin≤0.03-1.00.060.12100Moxifloxacin0.06-2.00.251100Gatifloxacin0.06-2.00.52100Levofloxacin≤0.03-1.00.060.25100Pip/tazobactam0.12-64.01890Imipenem≤0.03-1.00.120.5100氟喹询诺酮巡寿类对K.pn弦eu网mo乘ni应ae活性太比较喹诺税酮的挺特点举和副贡作用分代特点副作用I仅用于泌感IIaG-作用强，G+作用有限环丙对铜绿假单胞作用最强典型喹诺酮副作用IIb增强G+作用，铜绿假单胞作用减弱光毒性和QT间期延长明显IIIa增强G+作用无CYP450抑制IIIb明显增强G+作用无光毒性低CNS毒性Ⅳ无氟,抗阳性菌作用强副作用降低?Ba灶ll蓬P勇.壁JA模C盗20尖00穴;勤46汤:1世7-唯24细菌议耐喹绿诺酮门类机氏制×不同赢细菌并对左碰氧沙全星的慌耐药唇情况30扁%药物单次口服Cmaxmg/LTmax(h)T1/2(h)AUCmg·h/L生物利用度(%)蛋白结合率(%)尿回收(%)氧氟沙星400mg5.850.645.035.0902080环丙沙星500mg2.561.254.012.07036.740左氟沙星200mg2.690.926.2419.31003280加替沙星400mg4.11.47.833.5962682莫西沙星400mg3.12.51236914025吉米沙星320mg1.481.86.659.309056.935常用胶氟喹哗诺酮殿类药闻物PK比较FQ中枢颜神经与系统碑不良哥反应轻中呜度不恒良反已应头昏\头疼眩晕失眠视觉淋异常重度俊不良劈燕反应神志养异常幻觉抽搐/惊厥Dr腾ug舱,怕20客02结,6梦2:骄13絮-5明9CI废D炎19冰99桥,眨28记:3塞52言-3旱64FQ练C县NS不良充反应害机制招与率抑制GA增BA与受法体结铲合,刺激杂中枢很神经技系统,与其7位侧素链结伸构有滤关;其他体途径:N-甲基-D惩-门冬渐酰腺拿苷受馋体激林活;兴奋比性氨开基酸吴受体魂激活发生然率:Tr珠ov毙a>No良rf说,G吵at熄i,贱Mo雕xi>S政pa钓r>Ci效pr洋o>Of莫lo>Le盗vo氟喹肺诺酮悼致QT士c延长宫比较Td锋Poc成cu热rr升en手ce跟:Ci肃pr落of愚lo饰xa烟ci票n:涛0员.3穷/1少0设mi斑ll暮io活nLe灯vo胁fl丧ox芳ci翻n:士5土.4醒/1架0印mi刷ll炕io泳nGa底ti桐fl贫ox饰ac写in:辜27磨/1减0授mi给ll蹲io诱nQT俘cpr嫂ol嘉on熔ga金ti给on甩e驻ff吩ic千ac欣y:Sp煌ar蜓fl万ox粘ac宋in>gr朝ep袋af少lo呼xa插ci俱n>mo促xi哲fo作xa产ci羊n>ga岗ti扑fl惠ox雁ac级in>ge王mi彼fl象ox框ac吧in>le柏vo驴fl叔ox氏ac缘瑞in>c睡ip构ro约fl恼ox忌ac蹲inph匹ar捧ma猫co尼th峰er眼ap遵y促20消01卷.2亩1(剑12街):纳14乐68株-7膀2to居rs热ad量esdepo挺in亭te量s(幕Td章P)多因仍素效缎应肝损优害表乱现:转氨册酶升涝高黄疸肝衰开竭药物:曲伐吴沙星:撤市所有劝药物贱均有,程度休不同减而已氟喹经诺酮漂药物捕肝损项害FQ光毒耀性服用FQ后,暴露引部分粉皮肤炎出现蜜损害;可轻采可重,轻者忍红癍,重者娘出现却大疱窑性皮蒸炎;机制:FQ进入厘皮肤;受光(阳光\紫外居光等)照射,能量荷激发宗氧离狱子基陷团产酒生,启动能炎症嫩反应,破坏鸭皮肤.与FQ第8位基要团有冠关.光毒拍性强僵度:Lo察me刚,F掘le魄r>S悬pa乞r>En较or>Cl兵in>Tr哗ov>Ga芽ti>Mo话xi>Of渠lo令,C介ip着ro恢,N械or畏fFQ京8位基邪团与真光毒药物8位基团动物致毒剂量(mg/kg)NorfCH>300CiproCH>300OfloC-OR>300MoxiCH3OH>300GatiCH3OH>100TrovaN>100SparCF18ClinCF10司帕释沙星香对幼遮龄大澡鼠膝册关节箭软骨祝毒性瞎研究AA及C舱19拿98通,6仰:1肺47票0-侮14居75高剂钳量喹总诺酮责类与垂幼龄叠动物物关节景软骨叨毒性杰有关剂量(mg/kg)次/天时间(天)软骨病变600110/6600140/10600180/10600210/61800115/8环丙泳沙星/氧氟阿沙星碌对人碰体关过节软隙骨作很用的知体外艰研究AA初C涉19溜97裤,1相1:流25烈62倚-2谜56华5喹诺鼓酮类货对人品体软驻骨细乘胞有娃体外魂毒性喹诺朴酮类拼体外莫孵育14天,显微域镜下忆测量卸软骨壮细胞饮坏死骆与硫孔酸软纱骨素贤空泡霞数,药物阁与对谨照间匀差异壁明显,不同翁药物千间没荒有差盈异喹诺共酮类恭致软你骨损丙害幼龄治动物拆产生;动物妹种属否存在查差异:幼犬贼作用涌最明叹显;多发块生在胜负重此关节;与镁薯缺乏使有关;可能吊发生汤机制:影响手软骨桨细胞柿表面涛整合页素及涌其后瓣续反兄应;细胞俗内活糟性氧悠增加;抑制肆细胞DN拢A旋转里酶?现有恨研究快结果鼓表明:氟喹炎诺酮消不引活起儿计童关建节病风或者讲骨骼径异常;儿童旦对之烟耐受灯良好;临床恳感染励治疗守有效.美国猎儿科燥学会昏感染澡委员涂会推姨荐:在认葱真评聋估危为险与艳收益猫的情宽况下,可用迅于:囊性释纤维孟化患可者肺患支气曾管感钱染恶德化;复杂族性尿捷路感省染;长期杯用药盈的免塞疫抑催制个关体多英重耐奥药革川兰阴呢性菌裕感染;慢性磨骨髓闭炎;慢性收化脓戒性中惨耳炎;多重蓝耐药历结核闪杆菌按感染国外洒儿童箱应用野喹诺兔酮类唯意见Se蜘mi凳na尚rs僵i昂nPe帆di鸡ar秩icIn努fe翼ct沃io欣us失D辅is泳ea唉se葵s,挣1典99屠9,西10晨:3膀1-绣37FQ致血哪糖改删变现象:Ci作pr即o与磺准脲类停合用气致严鼠重低岛血糖;Le傻vo与糖买尿病样药合拢用致鸣低血掩糖;Mo令xi可致普磺脲静类浓现度降泳低,但未逝见血观糖改悼变;Ga爬ti与磺世脲类岔合用障致后坡者药傲效改接变,但未诸见药仅物相滔互作逃用糖尿赠病者贪高血陶糖或戏低血化糖正常陕人发纹生高勒血糖一般杠发生求在用涉药3天之踪蝶内Dr辅ug或,寄20怪02抚,6璃2:巩13扛-5爪9Am位J骡M滋ed穴,熟20恼02铃,享11留33幼:2呢32劲-2天34FQ致血宪糖改瘦变机野制与虚发生魂率可能罚与药钥物相垦互作刑用有像关影响范肾上浆腺素特分泌?影响蜻胰岛采细胞AT梨P钾通盟道,影响枪胰岛集素分够泌血糖CiproLevoGatiMoxi高血糖NA<1%<3%<0.1%低血糖<0.1%<0.1%<0.1%NA氟喹葛诺酮尺毒性匪构效欲关系Mg摔2+结合,软骨阴毒性?FNH半2,摇CH抚3遗传柜毒性P4荡50作用↑=虎C2喉H5小>光毒篇性,遗传艘毒性NH网2光毒币性↓>探>a伤lk打yl柏s淋ub<登<a膝lk南yl随s胃ubGA乡丰BA结合结晶珠尿NS缝AI蜓D作用bu捐lk档yP4典50作用↓bu趣lk阴yＣl,沿FO-骄CH固3结晶妄尿↓F>Ｃl>抽OC些H3P4拾50作用F>OM参eQT季c↑NH妇2>落CH削3>馆HQT移c↑喹诺拌酮副胖作用i副作用喹诺酮(频率)危险人群遗传毒性？？？孕妇胃肠道氟罗，司帕，格帕(>10％)光毒性司帕，氟罗，洛美(>10％)软骨培氟，其他(2.7%)儿童，孕妇肌腱炎培氟>>左氧/氧氟>环丙老人尤其在激素治疗中，运动员Va搬nBa彩mb社ek反eF,登e保t概al灶.Cl仿inMi达cr产ob斜io计lIn埋fe时ct坦2己00膜5;妻1个1:剑25张6-兄28瓶0副作用喹诺酮(频率)危险人群严重肝损伤曲伐(0.006%)严重CNS左氧：意识错乱(0.026%)

氟罗：失眠(8%)合用NSAID或CYP450抑制剂QT间期延长司帕(9-28ms)>格帕(10ms)>莫西(6ms)>左氧(3ms)>加替(2.9ms)合用可延长QT药或CYP450抑制剂低/高血糖加替，左氧合用口服降糖药CYP450抑制依诺>环丙>洛美>氧氟>左氧，司帕，加替，莫西喹诺锯酮副缠作用iiVa选nBa磁mb插ek萝eF,呀e堪t赶al恢.Cl而inMi蒸cr报ob饼io典lIn飘fe盖ct塑2常00浓5;铅1出1:梅25陆6-俯28锦0ND紧Aci绒noen继oxno摧rfPP霜Aof败loci泊pr萌oLe件vope谦flle肚mofl流ersp孤arto巷sute他matr很avcl个insi晓tage穷mipa导zuba览lopr寒ulmo病xiga光tigr玩epga聋requ咬in掌in族eru总fdi嘉fam削i苯吡具啶奈啶另酮泌尿率感染阴性剪菌感自染广谱丙药物呼吸废喹诺杆酮糖肽夺类药但物万古爬霉素替考厦拉宁Da认lb注av仙ac蹦inOr阴it树av楚ac产inTe呼la供va详ci颠n欧洲43家医冬院监牧测结塘果BacteriaYearStrainNoVancomycinTeicoplaninMICrMIC90MICrMIC90S.aureus2005337<0.25-21<0.12-8220062200.5-210.25-4120071310.5-210.25-412008690.25-210.25-41CoNS200593<0.25-420.25-1642006810.5-220.25->3282007810.5-220.25-842008910.25-220.12-84S.pyogenes2005410.250.25NtNt2006-----20071460.12-0.50.25<0.03-4<0.032008540.12-0.250.25<0.03-1<0.03Enterococci20053010.125-2562560.06-256642006-----2007720.25-220.5-20.2520081070.25->12820.25-1280.25EC破CM文ID老2榨00监9,忘p缩慧16楼20VA丛NC次OM逃YC斗IN垂A颠UC糠24山/M育IC、Cm缘瑞ax/M汇IC、T>宵MI洒C倍mi城ce元S凡.au异re霜usmi浑ce鉴t照hi痒gh松i越nf授ec摘ti泥onR2=9付0%-4-202-4-2021010嫩010疲001010苦010洋001-4-2024010则012妥00206080R2=5块6%R2=7李5%Fr毁ee裁d猪ru肚g昂AU苍C2昂4/亏MI跪CFr寸ee叔d净ru殊gCm锦ax/M职ICFr抓ee杏d姥ru果g浙%T虽>M照ICCF擦U漂ch弄an雨ge航i序n避Lg视10隙/t恰hi采gnCI向D兰2史00捕6,宗42挤(s邪up吧pl伶1签):啦S3恢5Va怀nc孝om诞yc安insa投fe炉ty项目FarberMellorSorrelCiminoDownsRybakGoetzSalamaElting年代198319851985198719891990199319931998设计回顾前瞻前瞻回顾前瞻前瞻前瞻前瞻前瞻例次94335481662316991747人群医疗医疗医疗肿瘤医疗医疗医疗医疗肿瘤总体肾毒%1617715171022717单独肾毒%590151351908合并AG者%35714152722241432耳毒%1125-----4静脉炎%13-37-14---3皮疹%3-6-0---11Ca隙nc番er19黎98势;8誉3:残25阿97恶唑介烷酮嫂类——利奈果唑烷OC3HHCNOONFONLinezolid(PNU-100766)Li胶ne颜zo皇li啊d抗菌后机制Li拒ne墓zo斤li朴d抗菌励谱Gr伪am胆-p蛮os英it掌iv娇e如mi愉cr