经验性抗感染治疗知识讲解.ppt

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1、经验经验性抗感染治性抗感染治疗疗Discovery of Antibacterial AgentsCycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycinImipenem19301940 195019601970198019902000PenicillinProntosilCephalosporin CEthambutolFusidic acidMupirocinNalidixic acidOxazolidinonesCecro

2、pinFluoroquinolonesNewer aminoglycosidesSemi-synthetic penicillins&cephalosporinsNewer carbapenemsTrinemsSynthetic approachesEmpiric screeningNewer macrolides&ketolidesRifampicinRifapentineSemi-synthetic glycopeptidesSemi-synthetic streptograminsNeomycinPolymixinStreptomycinThiacetazoneChlortetracyc

3、lineGlycylcyclinesMinocyclineChloramphenicol“Close the book on infectious disease”“Infectious disease will be with us for the foreseeable future”USSurgeonGeneralWilliamStewart,1969HarvardMedicalSchoolMaryWilson,1998抗生素时代感染仍是抗生素时代感染仍是人类健康的重要威胁人类健康的重要威胁IIIIIIII新出现或“再出现”的感染性疾病 emerging and re-emerging

4、infectious diseasesn新病原体不断出现-HIV/AIDS、Ebola、Hantavirus 新型肝炎、新型克雅病（疯牛病）肠杆菌O157、霍乱O139 环孢子菌病、隐孢子菌病、人类Ehrlichosisn老病卷土重来-肺结核、疟疾、鼠疫、霍乱、黄热病、登革热 和登革出血热n免疫缺陷人群不断增加-机会性真菌和呼吸道病毒性肺炎n细菌耐药愈演愈烈PRSP、MRSP、MRSA/MRSE、VRE、VISA/VERA ESBL、ampC、SSBL、金属酶.MDR结核菌 美国因细菌耐药增加医疗费用超过40亿美元!临床关注的耐药问题临床关注的耐药问题Resistances of Clinic

5、al Concerns革兰阳性细菌n金匍菌 MRSA,VISA,VRSAnVRE(地理上差别)n肺炎链球菌 青霉素和喹诺酮耐药 革兰阴性细菌n肠杆菌科ESBLsu喹诺酮,头孢菌素,青霉素类,氨基糖苷类u碳青霉烯类n非发酵菌(假单孢菌+/-不动杆菌)u喹诺酮,头孢菌素,青霉素类,氨基糖苷类,碳青霉烯类 Resistant bacteriaMutationsXXAntibiotic resistance:genetic events SusceptiblebacteriaResistant bacteriaGene transfer ResistantStrainsRarexxResistant

6、Strains DominantAntimicrobial Exposure xxxxxxxxxxSelection for Antimicrobial-Resistant Strains抗生素选择压力抗生素选择压力耐药菌的播散寻找新的抗感染药物寻找新的抗感染药物 -新药越来越少新药越来越少限制人以外限制人以外(畜牧业畜牧业)使用使用 -减少对人类的影响减少对人类的影响加强抗感染药物的临床管理加强抗感染药物的临床管理 -分级和分线分级和分线合理使用抗感染药物合理使用抗感染药物 加强医院感染的控制加强医院感染的控制 -减少耐药菌株院内传播减少耐药菌株院内传播 细菌耐药的临床对策 -Measure

7、s to Resistance减少抗生素选择性压力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，故抗生素必须覆盖所有可能的微生物，常选用联合治疗或单一广谱抗生素治疗性应用目标治疗：确定了病原体，选用窄谱、低毒性的抗生素预防性应用：Fighting infection in the first hoursRapid testsWhen available.Gram stain!Start adequate antibiotic coverage(within 1 hour?)Tillou A et al.Am Surg 2004;70:

8、841-4Tillou A et al.Am Surg 2004;70:841-4Drain purulent collectionSamplingIncluding invasive procedureswhen needed(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Factors Selected by Multivariate Analysis Independently Related to MortalityVariableRelative O.R.p ValueUnderlying disease(UF+RF)3.09.0007Shoc

9、k2.850.016Bacteremia2.630.019Ineffective Initial Therapy4.71.0001LeroyOIntensive Care Med1995;21:24-31Importance of Adequate and Appropriate Antimicrobial TreatmentAdequate antimicrobial treatmentMortalityIncreasedDecreasedInadequate antimicrobial treatmentOngoingbacterialproliferationandinflammatio

10、nselectionofdrug-resistantmicroorganismsEwigetal,Thorax2002;57:366Effect of Early Administration of Antibiotics on OutcomesHouckPMetal.Arch Intern Med2004;164:637-44VariableAll patientsAntibiotics within 4 hoursAntibiotics after 4 hoursAdjusted Odds Ratiop Value30-day mortality12.011.612.70.85.005In

11、-hospital mortality7.06.87.40.85.03%of patients with LOS5 d43.342.145.10.90.00330-day readm rate13.413.113.90.95.34Early Administration of Abx significantly decrease mortality and LOSStart empirical antibiotic therapy as soon as possible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

12、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Cryptogenic Organizing PneumoniaInfectious Diseases Expert ResourcesInfectious Diseases SpecialistsOptimal Optimal Patient CarePatient CareInfectionControlProfessionalsHealthca

13、reEpidemiologistsClinicalPharmacistsClinicalPharmacologistsSurgicalInfectionExpertsClinicalMicrobiologists选择哪种抗菌药物(which antibiotic?)感染部位的常见病原学(possible pathogens on site of infection)选择能够覆盖病原体的抗感染药物(antibiotics requirement)-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(physiologic and patho

14、physiology)高龄/儿童/孕妇/哺乳(advanced age/children/pregnant women/breast feeding)肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(other considerations)杀菌和抑菌/单药和联合/静脉和口服/疗程 (cidal vs static/mono vs combination/IV vs PO/duration)经验性抗感染治疗合理选择药物-considerations in choosing antibiotic for empiric the

15、rapy l培养结果前依据基本信息选择抗感染药物 choosing Abx before culture result感染部位和可能病原体的关系 association of pathogen with site of infectionGram染色结果-与上述病原体是否符合？Gram stain-in accordance with suspected pathogen?l某些病原体易于造成某些部位的感染 Some pathogen easily cause some site of infection 经验性抗感染治疗药物选择-considerations in choosing anti

16、biotic for empiric therapy 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)通读药物说明书和相关资料组织穿透性(tissue penetration)抗菌药物的特性（antibiotic itself）脂溶性(lipid sol

17、ubility)/分子量(MW)组织特性（血运/炎症）(tissue itself-blood supply and inflammation)急性感染/慢性感染(acute vs chronic infection)细胞内病原体(intra vs extracellullar pathogen)体内特殊生理屏障(physiologic barriers)-血脑屏障、血胰屏障、胎盘屏障等耐药性(resistance,specifically local resistance)参考代表性资料/依靠当地资料安全性(safety profile)-药物本身/制剂/工艺/杂质费用/效益(cost/ef

18、fectiveness)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能够覆盖可能病原体的抗菌药物（Abx requirements）血脑屏障：多数抗菌药物脑脊液浓度很低脂溶性溶性较高、非极性、蛋白结合率低者易通过血脑屏障炎症时血脑屏障通透性可增加体内特殊生理屏障胎盘屏障：几乎所有抗菌药物都能穿透胎盘屏障进入胚胎循环在妊娠期应避免使用对胎儿发育有影响的抗菌药物 氯霉素、氨基糖苷类、四环素类、磺胺类、氟喹诺酮类、利福平等 抗菌药物在脑脊液中分布 氯霉素氯霉素青霉素青霉素万古霉素万古霉素链霉素链霉素两性霉素两性霉素B B磺胺药磺胺药氨苄西林氨苄西林阿米卡星阿米卡星庆大霉素庆大霉素林可霉素林可霉

19、素吡嗪酰胺吡嗪酰胺羧苄西林羧苄西林奈替米星奈替米星妥布霉素妥布霉素多粘菌素多粘菌素B B异烟肼异烟肼哌拉西林哌拉西林头孢孟多头孢孟多红霉素红霉素克林霉素克林霉素利福平利福平头孢噻肟头孢噻肟头孢哌酮头孢哌酮苯唑西林苯唑西林乙胺丁醇乙胺丁醇头孢他啶头孢他啶甲硝唑甲硝唑头孢呋新头孢呋新美洛西林美洛西林环丙沙星环丙沙星拉氧头孢拉氧头孢磷霉素磷霉素阿昔洛韦阿昔洛韦亚胺培能亚胺培能阿糖腺苷阿糖腺苷脑脑膜膜炎炎症症或或无无炎炎症症时时csfcsf浓浓度度均均可可达达到到抑抑菌菌水平（水平（MIC)MIC)仅仅在在脑脑膜膜炎炎症症时时csfcsf浓浓度度均均可可达达到到抑抑菌菌水水平平（MICMIC）脑脑膜膜

20、炎炎症症时时csfcsf可可达达一定浓度一定浓度脑脑膜膜炎炎症症时时csfcsf浓浓度度仍仍呈微量者（呈微量者（60years2.65Diabetes2.57Colodneret al EJCMID200423,163.Prevalence of rectal carriage of Extended-Spectrum-lactamase-producing Escherichia Coli among elderly people in a community setting in Shenyang 横断面研究/整群抽样-276名社区老人、直肠拭子/大肠杆菌ESBL检测、分子分型和PEGF结

21、果:直肠拭子ESBL+大肠杆菌携带率7.0%（19/270）.19株ESBL+菌株ESBL基因型均为CTX-M 型 12株为CTX-M-14 型（63.2%),3株 CTX-M-22型,1株 CTX-M-24型，2株 CTX-M-57-like型，1株同时产CTX-M-24和CTX-M-57-like型.序列分析表明CTX-M-57-like基因序列中第865位点发生GA替换,导致 氨基酸序列中第289位点发生DN替换,该基因序列不同于 GenBank数 据库已发表序列，提示新型ESBLs基因型(GenBank 序列号 EF426798)TianSF,ChenBY.Prevalenceofre

22、ctalcarriageofExtended-Spectrum-lactamase-producingEscherichiaColiamongelderlypeopleinacommunitysettinginShenyang,China.CanadianJournalofmicrobiology2008;54:1519株产ESBLs的大肠埃希菌的PFGE图谱左起依次为：Marker，菌株编号T2-S28.产ESBLs菌株PFGE图谱呈多样性，提示社区产ESBLs的大肠埃希菌为多克隆起源 Univariate analysis of risk factors for carriage of E

23、SBL-producing Escherichia coli in the community(n=270)PotentialRiskfactorsNo(%)ESBLsTotalNoOddsratio(95%CI)PvalueAge(years)7416(7.4)216753(5.6)540.74(0.21-2.62)0.77GenderFemale12(7.8)153Male7(6.0)1170.81(0.31-2.13)0.81DiabetesNo11(6.3)174Yes8(8.3)961.35(0.52-3.47)0.62HospitalizationinpastoneyearNo18

24、(6.8)264Yes1(16.7)62.73(0.30-24.66)0.34SurgeryinpastoneyearNo19(7.1)268Yes0(0)20.00.8UseofantibioticinpastthreemonthsNo12(5.3)227Yes7(16.3)433.48(1.29-9.44).018产ESBL细菌感染的危险因素Prospective study of 455 episodes of K.pneumoniae bacteremia(253 nosocomial)in 12 hospitalsn30.8%为医院获得,ICU中43.5%产ESBLsnESBLs危险

25、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2 d(OR=3.9).n其它危险因素 TPN,肾功衰竭,烧伤n非ESBL危险:碳青霉烯、头孢吡肟、喹诺酮、氨基糖苷类 Paterson et al:Ann Intern Med 2004;140:26-32.VAP耐药菌感染的危险因素135 次VAP ICU变量 OR PMV7 days 6.0 .009先期ABs 13.5 7 days/prior ABsTrouillet,et al.Am J Respir Crit Care Med.1998;157:531Trouillet JL et al.Clin Infect Dis.2

26、002;34:1047-1054.铜绿VAP:34株派拉西林耐药;101株派拉西林敏感n发生VAP15天内使用抗菌药（亚胺培南,3代头孢和喹诺酮)增加铜绿对同种药物的耐药性aP=.0009 bP=.003 cP=.001 dP=.05Resistance of P aeruginosa Strains To Imipenem,Ceftazidime,or Ciprofloxacin,According to Previous Therapy With Imipenem,a 3rd-generation Cephalosporin,or a FluoroquinoloneNo.(%)of pat

27、ients,by previous drug therapy receivedImipenemThird-generation cephalosporinFluoroquinoloneStrain resistanceNo(n=114)Yes(n=21)No(n=73)Yes(n=62)No(n=100)Yes(n=35)To imipenem19(16.7)11(52.4)a12(16.4)18(29.0)18(18)12(34.3)dTo ceftazidime17(14.9)7(33.3)6(8.2)18(29.0)b14(14)10(28.6)To ciprofloxacin35(30

28、.7)11(52.4)25(34.2)21(33.9)26(26)20(57.1)c关注耐药病原体-近期应用抗菌药物与铜绿耐药S.aureusPenicillin1944Penicillin-resistantS.aureus金黄色葡萄球菌耐药的发生发展过程金黄色葡萄球菌耐药的发生发展过程Methicillin1962Methicillin-resistantS.aureus(MRSA)Vancomycin-resistantenterococci(VRE)Vancomycin1990s1997VancomycinintermediateS.aureus(VISA)2002Vancomycin

29、-resistantS.aureusCDC,MMWR2002;51(26):565-5671960Macrolide resistant S.pneumoniae in Asian Countries:ANSORP 1998-2001-555isolates-macrolidesusceptibility-216S(38.9%)-10I(1.8%)-329R(59.3%)Vietnam88.3%RHongKong76.5%RTaiwan87.2%RChina75.6%RKorea85.1%R-ermBmorecommon(50%)China,Taiwan,SriLanka,Korea.-mef

30、AmorecommonHongKong,Singapore,Thailand,Malaysia.-mostcountriesMIC9012mg/L.Song et al,JournalofAntimicrobialChemotherapy2004;53(3):457-463.红霉素耐药肺炎链球菌表型和基因型赵铁梅，刘又宁.中华内科杂志.2004;43(5):329-332/AAC,2004;48（10）:4040-4041耐药表型耐药表型基因型基因型N=148抗菌谱(coverage)通读药物说明书和相关资料组织穿透性(tissue penetration)抗菌药物的特性（antibiotic

31、 itself）脂溶性(lipid solubility)/分子量(MW)组织特性（血运/炎症）(tissue itself-blood supply and inflammation)急性感染/慢性感染(acute vs chronic infection)细胞内病原体(intra vs extracellullar pathogen)体内特殊生理屏障(physiologic barriers)-血脑屏障、血胰屏障、胎盘屏障等耐药性(resistance,specifically local resistance)参考代表性资料/依靠当地资料安全性(safety profile)-药物本身/

32、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能够覆盖可能病原体的抗菌药物（Abx requirements）评估责任病原体评估病原体耐药性Avoiding the adverse outcomes of resistanceindividual patient perspective应用耐药可能性低的药物到位！治疗决定个体化u耐药的可能性？l病人的致病微生物？病人来源?l选择压力用当地的监测资料不越位！u耐药u交叉耐药资料选择哪种抗菌药物(which antibiotic?)感染部位的常见病原学(possible path

33、ogens on site of infection)能够覆盖病原体的抗感染药物(antibiotics requirement)抗菌谱coverage)/组织穿透性(tissue penetration)/耐药性(resistance pattern)/安全性(safety)/费用(cost)优化药代动力学/药效动力学(optimizing PK/PD)考虑病人生理和病理生理状态(physiologic and pathophysiology)高龄/儿童/孕妇/哺乳(advanced age/children/pregnant women/breast feeding)肾功能不全/肝功能不全

34、/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(other considerations)杀菌和抑菌/单药和联合/静脉和口服/疗程 合理的经验性抗感染治疗药物选择 considerations in choosing antibiotic for empiric therapyPharmacology of Antimicrobial TherapyDosingregimenConcentrationsinserumConcentrationsintissuesandbodyfluidsConcentrationsatsiteofinfecti

35、onPharmacologicandtoxicologiceffectAntimicrobialeffectAbsorptionAbsorptionDistributionDistributionEliminationEliminationPharmacokinetics(PK)PharmacodynamicsPharmacodynamics(PD)(PD)MIC、MBCDifferent pattern of time-killing of 3 Abx VS PseudomonasKilling and rate of killing depends on concentrationRate

36、 of killing increases no more as concentration increases,killing depends on exposure timePK/PD Predictors of Efficacy-a combination of PK and PDTimeMIC90LogConcentration24h-AUCTMICCmax,Cmax/MIC24h-AUC/MIC(AUIC)DoseDoseCmaxTMICParameters of interestPK/PD Predictors of Efficacy依据依据PK/PDPK/PD抗菌药物分类抗菌药物

37、分类时间依赖性时间依赖性与时间有关，但抗菌活性持续时与时间有关，但抗菌活性持续时间较长间较长对致病菌的杀菌作用对致病菌的杀菌作用取决于峰浓度取决于峰浓度抗菌作用与抗菌作用与同细菌接触时间密切相关同细菌接触时间密切相关时间依赖且时间依赖且PAEPAE或或T1/2T1/2较长较长 氨基糖苷类、氟喹诺酮类、氨基糖苷类、氟喹诺酮类、酮内酯类、两性霉素酮内酯类、两性霉素B B、daptomycin daptomycin、甲硝唑甲硝唑多数多数-内酰胺类、内酰胺类、林可霉素类林可霉素类恶唑烷酮类、氟胞嘧啶恶唑烷酮类、氟胞嘧啶 链阳霉素、四环素、链阳霉素、四环素、碳青霉烯类、糖肽类、碳青霉烯类、糖肽类、大环内

38、酯类、唑类抗真菌药大环内酯类、唑类抗真菌药 主要参数主要参数AUC0-24/MIC(AUIC)Cmax/MIC 主要参数主要参数 TMIC和和AUCMIC主要参数主要参数 TMIC,PAE，T1/2 AUC/MIC 浓度依赖性浓度依赖性Required%TMIC for cidal:n 40%for carbapenemsn 50%for penicillinsn 70%for cephalosporinsDrusano GL.Clin Infect Dis.2003;36(suppl 1):S42-S50.Required%TMICforstatic20%forcarbapenems30%f

39、orpenicillins40%forcephalosporins-lactam:optimal TMIC?Drusano.Clin Infect Dis 2003;36(Suppl.1):S42S50Maximizing TMIC提高剂量安全性前体增加给药频率延长输注时间-内酰胺类优化暴露时间-Lactam:Optimizing ExposureDandekarPKetal.Pharmacotherapy.2003;23:988-991.Meropenem 500 mg Administered as a 0.5 h or 3 h InfusionMIC024680.11.010.0100.

40、0ConcentrationConcentration(mcg/mL)(mcg/mL)Time(h)Time(h)RapidInfusion(30min)ExtendedInfusion(3h)Treatment of Multidrug-resistant Burkholderia cepacia With Prolonged Infusion MeropenemMeropenem 2 g infused over 3 hours q 8 hMeropenem 2 g infused over 3 hours q 8 hTime(h)Time(h)ConcentrationConcentra

41、tion(mcg/mL)(mcg/mL)08162432400.1110100MIC=16mcg/mLTMICexposurewas40%ofthedosingintervalattheMICof16mcg/mLKutiJLetal.Pharmacotherapy.2004;24:1641-1645Moore et al.J Infect Dis 1987;155:9399Aminoglycoside:optimal Aminoglycoside:optimal C Cmaxmax:MIC:MIC -Relationship Between C-Relationship Between Cma

42、xmax:MIC and Clinical Response:MIC and Clinical ResponseClinical response(%)Clinical response(%)C Cmaxmax:MIC:MIC0 020204040606080801001002 24 46 68 810101212555565657070838389899292What is the Optimal AUIC for Fluoroquinolones?30125For G+For G-Forrest et al.Antimicrob Agents Chemother 1993;37:10731

43、081Fluoroquinolone Therapy for Nosocomial PneumoniaFluoroquinolone Therapy for Nosocomial Pneumonia Correlation Between Drug Exposure(AUC/MIC)&OutcomeCorrelation Between Drug Exposure(AUC/MIC)&OutcomePatients cured(%)Patients cured(%)0 02020404060608080100100062.5062.562.512562.512512525012525025050

44、0250500500500AUC:MICAUC:MICClinicalClinicalMicrobiologicalMicrobiologicalAUC:MIC125 lead to appropriate clinical and microbiological outcomeGram-Negative Bacterial Eradication and Fluoroquinolone AUICDays 0 2 4 6 8 10 12 140100755025AUIC 125-250AUIC 250AUIC 125%Patients remaining culture positiveFor

45、restetal.Antimicrob Agents Chemother.1993;37:1073-1081Higher AUC:MIClead to letter bacterial eradicationProbability of Developing ResistanceProbability of Developing ResistanceThomas KL et al.Thomas KL et al.Antimicrob Agents ChemotherAntimicrob Agents Chemother.1998;42:521527.1998;42:521527AUCAUC02

46、4h024h:MIC:MIC 100100AUCAUC024h024h:MIC 100:MIC 100 Free AUIC 30-40Resistance preventionnCmax MPCnHigher AUICBaquero&Negri.BioEssays1997;19:731-6DrlicaK.ASMNews2001;67:27-33Cantnetal.InterJAntimicrobChemother2006(inpress)Concentration (g/ml)Time post administration(h)CmaxMPCTmax MICWindow of selecti

47、onMICMPC(MIC of mutants)Resistant mutantSusceptible bacteria选择哪种抗菌药物(which antibiotic?)感染部位的常见病原学(possible pathogens on site of infection)能够覆盖病原体的抗感染药物(antibiotics requirement)抗菌谱coverage)/组织穿透性(tissue penetration)/耐药性(resistance pattern)/安全性(safety)/费用(cost)优化药代动力学/药效动力学(optimizing PK/PD)考虑病人生理和病理生

48、理状态(physiologic and pathophysiology)高龄/儿童/孕妇/哺乳(advanced age/children/pregnant women/breast feeding)肾功能不全/肝功能不全/肝肾功能联合不全(renal/heptic dysfunction/combined)其它因素(other considerations)杀菌和抑菌/单药和联合/静脉和口服/疗程 合理的经验性抗感染治疗药物选择 considerations in choosing antibiotic for empiric therapy老人感染特点o易发生细菌感染o常见肺炎、尿感、胆道

49、感染、败血症o常见菌:G-杆、金葡、肺球、肠球、真菌老人抗菌药药理o肾功减退，半减期长，血浓度高o肝解毒功能降低o组织退化、防御功能低，胃、尿、胆汁中常有菌o水量减少，药物在脂肪中浓度高o白蛋白减少，游离药物多老人抗菌治疗o宜用杀菌剂o避免肾毒性药物o有条件的做TDM(特别用肾毒性药物时)o不良反应多，且不易发现o肝肾清除减退剂量宜低、分次给药o注意全身状态心功能、水盐平衡小儿抗菌药药理o药物酶系不成熟，血浓度偏高o肾发育不全，药物排泄减少o胞外溶液量大，药物消除慢o与血浆蛋白结合松，游离药物多小儿抗菌治疗o剂量宜低o避免应用毒性明显的药物：氨基糖甙、多粘、磺胺、呋喃、喹诺酮o避免肌注o血容积

50、大，肾血流量大，分布容积大o剂量宜增，对药物毒性敏感o药物通过胎盘，影响胎儿孕妇抗菌药药理药物可自乳汁分泌，无论乳汁中药物浓度如何，均存在对乳儿潜在的影响，并可能出现不良反应哺乳期应用任何抗菌药物时，均宜暂停哺乳乳汁中含量较高n喹诺酮、四环素类、大环内酯类、氯霉素、磺胺、甲氧苄啶、甲硝唑、异菸肼、乳汁含量较低n青霉素类、头孢菌素类、氨基糖苷类哺乳期患者抗菌药物的应用抗微生物药在妊娠期应用时的危险性分类FDA分类分类 抗微生物药抗微生物药A.在孕妇中研究证实无危险性在孕妇中研究证实无危险性B.动物中研究无危险性，但人类动物中研究无危险性，但人类 研究资料不充分，或对动物有研究资料不充分，或对动物