1、抗感染药物发展简史抗感染药物发展简史1929 Alexander Fleming 发现青霉素发现青霉素1939 Howard Florey 和和 Ernst Chain分离获得青霉素，用于动物试验。分离获得青霉素，用于动物试验。1942 青霉素首次用于救治战伤患者，拯救了青霉素首次用于救治战伤患者，拯救了 许多人的生命许多人的生命1950s 大量抗生素用于临床。大量抗生素用于临床。A poster from World War II,dramatically showing the virtues of the new miracle drug,and representing the hig
2、h level of motivation in the country to aid the health of the soldiers at war.Discovery of Antibacterial AgentsCycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycinImipenem19301940195019601970198019902000PenicillinProntosilCephalosporin CEth
3、ambutolFusidic acidMupirocinNalidixic acidOxazolidinonesCecropinFluoroquinolonesNewer aminoglycosidesSemi-synthetic penicillins&cephalosporinsNewer carbapenemsTrinemsSynthetic approachesEmpiric screeningNewer macrolides&ketolidesRifampicinRifapentineSemi-synthetic glycopeptidesSemi-synthetic strepto
4、graminsNeomycinPolymixinStreptomycinThiacetazoneChlortetracyclineGlycylcyclinesMinocyclineChloramphenicol“Close the book on infectious disease”“Infectious disease will be with us for the foreseeable future”US Surgeon General William Stewart,1969Harvard Medical School Mary Wilson,1998IIIIIIII新出现或“再出现
5、”的感染性疾病 emerging and re-emerging 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
6、药问题临床关注的耐药问题Resistances of Clinical 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Newer macrolides&ketolides留取标本进行微生物学检查AUC024h:MIC 5 d43.342.145.10.90.00330-day readm rate13.413.113.90.95.34Early Ad
7、ministration of Abx significantly decrease mortality and LOSStart empirical antibiotic therapy as soon as possible慢性咳嗽和黄痰慢性咳嗽和黄痰-原因原因哮喘哮喘 后鼻腔鼻漏后鼻腔鼻漏病毒感染后气道高反应性病毒感染后气道高反应性胃酸返流胃酸返流吸烟相关的慢性支气管炎吸烟相关的慢性支气管炎支气管扩张症支气管扩张症弥漫性泛细支气管炎弥漫性泛细支气管炎肺泡蛋白沉积症肺泡蛋白沉积症急性发热急性发热 WBCWBC不高不高/淋巴增高（无感染灶）病毒！淋巴增高（无感染灶）病毒！WBCWBC增高增高
8、/中性粒增高中性粒增高/核左移核左移 可能细菌！可能细菌！部位部位/病原体？病原体？原发性菌血症？原发性菌血症？慢性发热慢性发热 IEIE、布病、慢性感染灶？结核病？、布病、慢性感染灶？结核病？非感染性发热非感染性发热 药物热、风湿病、恶性肿瘤药物热、风湿病、恶性肿瘤正确诊断是正确治疗的前提正确诊断是正确治疗的前提发热的诊断与鉴别诊断发热的诊断与鉴别诊断Infectious Diseases Expert ResourcesInfectious Diseases SpecialistsOptimal Patient CareInfection Control ProfessionalsHeal
9、thcare EpidemiologistsClinicalPharmacistsClinical PharmacologistsSurgical InfectionExpertsClinicalMicrobiologistsMDR结核菌水量减少，药物在脂肪中浓度高-高龄、基础疾病、近期使用抗菌药物、住院Resistance prevention-绿脓杆菌肺炎并菌血症经验性抗感染治疗合理选择药物-considerations in choosing antibiotic for empiric therapyFluoroquinolones1998;42:521527Healthcare47)
10、0.J Med Microbiol 1999，48：6771Effect of Early Administration of Antibiotics on Outcomes全球华人临床微生物和感染病学会 理事Antimicrob Agents Chemother.Yes 7(16.Fluoroquinolone(%)of patients,by previous drug therapy receivedGram-Negative Bacterial Eradication and Fluoroquinolone AUICHospitalization in past one year抗菌药
11、物的特性（antibiotic itself）Surgical Infection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 pathophysiology)高龄/儿童/孕妇/哺乳(advanced age/children/pregnant women/breas
12、t 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 therapy 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
13、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经验性抗感染治疗药物选择-considerations in choosing antibiotic for empiric therapy 不同感染部位的常见感染性病原体不同感染部位的常见感染
14、性病原体Possible pathogens on site of infection注意特殊修正因子注意特殊修正因子/特别是先期抗菌药物对细菌学的影特别是先期抗菌药物对细菌学的影响响 不同感染部位的常见感染性病原体不同感染部位的常见感染性病原体Possible pathogens on site of infection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重症军团菌肺炎发热、少痰发热、少痰多肺叶、多肺段受累多肺叶、多肺段受累肺外表现肺外表现抗菌谱(coverage)通读药物说明书和相关资料组织穿透性(tissue penetration)抗菌
15、药物的特性（antibiotic 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(safet
16、y profile)-药物本身/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（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抗菌药物
17、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 脑膜炎症或无炎症时脑膜炎症或无炎症
18、时csfcsf浓度均可达到抑菌浓度均可达到抑菌水平（水平（MIC)MIC)仅在脑膜炎症时仅在脑膜炎症时csfcsf浓浓度均可达到抑菌水平度均可达到抑菌水平（MICMIC）脑膜炎症时脑膜炎症时csfcsf可达可达一定浓度一定浓度 脑膜炎症时脑膜炎症时csfcsf浓度仍浓度仍呈微量者（呈微量者（7 days 6.失败或副作用致再治疗费用更高Forrest et al.抗菌谱(coverage)通读药物说明书和相关资料组织特性（血运/炎症）(tissue itself-blood supply and inflammation)MinocyclineAntibiotics within 4 hour
19、sAcute infectionGram stain-in accordance with suspected pathogen?抗生素时代感染仍是人类健康的重要威胁丹麦学者对19811995的14年间7938次菌血症分离的8840菌株进Epidemiologists1998;42:521527Early Administration of Abx significantly decrease mortality and LOSTo ceftazidime丹麦学者对19811995的14年间7938次菌血症分离的8840菌株进留取标本进行微生物学检查多少胃肠道副作用Yes 7(16.是否耐药菌
20、？依据宿主相关因素Risk factors for infection with ESBL producers outside hospitalFactorOdds ratioRx 3 gen ceph15.8Rx 2 gen ceph10.1Hospital in last 3 months8.95Rx quinolone4.1Rx penicillins4.0Antibiotic Rx in last 3 months3.23Age 60 years2.65Diabetes2.57Colodner et al EJCMID 2004 23,163.Prevalence of rectal
21、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CT
22、X-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)Tian SF,Chen BY.Prevalence of rectal carriage of Extended-Spectrum-lactamase-producing Escherichia Coli among elderly people in a community setting in Shenyang
23、,China.Canadian Journal of microbiology 2008;54:1519株产株产ESBLs的大肠埃希菌的的大肠埃希菌的PFGE图谱图谱左起依次为：左起依次为：Marker，菌株编号，菌株编号T2-S28.产产ESBLsESBLs菌株菌株PFGEPFGE图谱呈多样性，图谱呈多样性，提示社区产提示社区产ESBLsESBLs的大肠埃希菌为多克隆起源的大肠埃希菌为多克隆起源 Univariate analysis of risk factors for carriage of ESBL-producing Escherichia coli in the communit
24、y(n=270)Potential Risk factors No(%)ESBLs Total No Odds ratio(95%CI)P value Age(years)74 16(7.4)216 75 3(5.6)54 0.74(0.21-2.62)0.77 Gender Female 12(7.8)153 Male 7(6.0)117 0.81(0.31-2.13)0.81 Diabetes No 11(6.3)174 Yes 8(8.3)96 1.35(0.52-3.47)0.62 Hospitalization in past one year No 18(6.8)264 Yes 1
25、(16.7)6 2.73(0.30-24.66)0.34 Surgery in past one year No 19(7.1)268 Yes 0(0)2 0.0 0.8 Use of antibiotic in past three months No 12(5.3)227 Yes 7(16.3)43 3.48(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
26、ESBLsnESBLs危险因素 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
27、 Infect Dis.2002;34:1047-1054.铜绿铜绿VAP:34株派拉西林耐药株派拉西林耐药;101株派拉西林敏感株派拉西林敏感n发生发生VAP15天内使用抗菌药（亚胺培南天内使用抗菌药（亚胺培南,3代头孢和喹诺酮代头孢和喹诺酮)增加铜绿对同种药物的耐药性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,
28、a 3rd-generation Cephalosporin,or a FluoroquinoloneNo.(%)of patients,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
29、(14.9)7(33.3)6(8.2)18(29.0)b14(14)10(28.6)To ciprofloxacin35(30.7)11(52.4)25(34.2)21(33.9)26(26)20(57.1)c关注耐药病原体关注耐药病原体-近期应用抗菌药物与铜绿耐药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-resistanten
30、terococci(VRE)Vancomycin1990s1997VancomycinintermediateS.aureus(VISA)2002Vancomycin-resistantS.aureusCDC,MMWR 2002;51(26):565-5671960Macrolide resistant S.pneumoniae in Asian Countries:ANSORP 1998-2001-555 isolates-macrolide susceptibility-216 S(38.9%)-10 I (1.8%)-329 R(59.3%)Vietnam88.3%RHong Kong
31、76.5%RTaiwan87.2%RChina75.6%RKorea85.1%R-ermB more common(50%)China,Taiwan,Sri Lanka,Korea.-mefA more common Hong Kong,Singapore,Thailand,Malaysia.-most countries MIC90 12 mg/L.Song et al,Journal of Antimicrobial Chemotherapy 2004;53(3):457-463.;4343(5)(5):329-332/:329-332/AAC,2004;48AAC,2004;48（101
32、0）:4040-40414040-4041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 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 b
33、arriers)-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/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（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
34、 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 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(opti
35、mizing 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/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 therapyPh
36、armacology of Antimicrobial TherapyDosingregimenConcentrationsin serumConcentrationsin tissues and body fluidsConcentrationsat site of infectionPharmacologic and toxicologic effectAntimicrobialeffectPharmacokinetics(PK)MIC、MBCDifferent pattern of time-killing of 3 Abx VS PseudomonasKilling and rate
37、of killing depends on concentrationRate of killing increases no more as concentration increases,killing depends on exposure timeOther considerations in choosing Abx军团菌、肺炎链球菌都可致重症感染考虑病人生理和病理生理状态(physiologic and pathophysiology)结果:直肠拭子ESBL+大肠杆菌携带率7.choosing Abx before culture result+respiratory FQ5 h
38、or 3 h InfusionInfection ControlProspective study of 455 episodes of K.Newer aminoglycosidesVirginiamycinOptimizing FQs therapy for S.44).MV7 days 6.GlycylcyclinesChristensenB,et al antibiotic resistance patterns among bulood culture isolates in a Dansis county 19811995。有条件的做TDM(特别用肾毒性药物时)多数抗菌药物脑脊液浓
39、度很低Patient Care耐药性(resistance,specifically local resistance)Canadian Journal of microbiology 2008;54:15失败或副作用致再治疗费用更高PK/PD Predictors of Efficacy-a combination of PK and PDTimeMIC90Log Concentration24h-AUCT MICCmax,Cmax/MIC24h-AUC/MIC(AUIC)DoseDoseCmaxTMICParameters of interestPK/PD Predictors of Ef
40、ficacy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
41、、大环内酯类、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%TMIC for static 20%for carbape
42、nems 30%for penicillins 40%for cephalosporins -lactam:optimal TMIC?Drusano.Clin Infect Dis 2003;36(Suppl.1):S42S50Maximizing TMIC提高剂量安全性前体提高剂量安全性前体增加给药频率增加给药频率延长输注时间延长输注时间-内酰胺类优化暴露时间-Lactam:Optimizing ExposureDandekar PK et al.Pharmacotherapy.2003;23:988-991.Meropenem 500 mg Administered as a 0.5 h
43、or 3 h InfusionMIC024680.11.010.0100.0Rapid Infusion(30 min)Extended Infusion(3 h)Treatment of Multidrug-resistant Burkholderia cepacia With Prolonged Infusion Meropenem08162432400.1110100MIC=16 mcg/mLTMIC exposure was 40%of the dosing interval at the MIC of16 mcg/mLKuti JL et al.Pharmacotherapy.200
44、4;24:1641-1645Moore et al.J Infect Dis 1987;155:9399Aminoglycoside:optimal Cmax:MIC -Relationship Between Cmax:MIC and Clinical ResponseClinical response(%)Cmax:MIC02040608010024681012556570838992What is the Optimal AUIC for Fluoroquinolones?30125For G+For G-Forrest et al.Antimicrob Agents Chemother
45、 1993;37:10731081Fluoroquinolone Therapy for Nosocomial Pneumonia Correlation Between Drug Exposure(AUC/MIC)&OutcomePatients cured(%)020406080100062.562.5125125250250500500AUC:MICClinicalMicrobiologicalAUC:MIC125 lead to appropriate clinical and microbiological outcomeGram-Negative Bacterial Eradica
46、tion and Fluoroquinolone AUICDays 0 2 4 6 8 10 12 140100755025AUIC 125-250AUIC 250AUIC 125%Patients remaining culture positiveForrest et al.Antimicrob Agents Chemother.1993;37:1073-1081Higher AUC:MIClead to letter bacterial eradicationProbability of Developing ResistanceThomas KL et al.Antimicrob Ag
47、ents Chemother.1998;42:521527AUC024h:MIC 100AUC024h:MIC 100 Free AUIC 30-40Resistance preventionnCmax MPCnHigher AUICBaquero&Negri.BioEssays 1997;19:731-6 Drlica K.ASM News 2001;67:27-33Cantn et al.Inter J Antimicrob Chemother 2006(in press)Concentration (g/ml)Time post administration(h)CmaxMPCTmax
48、MICWindow of selectionMICMPC(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(optimiz
49、ing 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/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
50、点老人感染特点o易发生细菌感染易发生细菌感染o常见肺炎、尿感、胆道感染、败常见肺炎、尿感、胆道感染、败血症血症o常见菌常见菌:G-:G-杆、金葡、肺球、肠球、杆、金葡、肺球、肠球、真菌真菌老人抗菌药药理老人抗菌药药理o肾功减退，半减期长，血浓度高肾功减退，半减期长，血浓度高o肝解毒功能降低肝解毒功能降低o组织退化、防御功能低，胃、尿、组织退化、防御功能低，胃、尿、胆汁中常有菌胆汁中常有菌o水量减少，药物在脂肪中浓度高水量减少，药物在脂肪中浓度高o白蛋白减少，游离药物多白蛋白减少，游离药物多老人抗菌治疗老人抗菌治疗o宜用杀菌剂宜用杀菌剂o避免肾毒性药物避免肾毒性药物o有条件的做有条件的做TDM(
