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1、抗感染药物发展简史1929 Alexander Fleming 发现青霉素1939 Howard Florey 和 Ernst Chain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，拯救了许多人的生命1950s 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 high level of motivation in the country to aid the health of the sold
2、iers at war.Discovery of Antibacterial AgentsCycloserineErythromycinEthionamideIsoniazidMetronidazolePyrazinamideRifamycinTrimethoprimVancomycinVirginiamycinImipenem19301940195019601970198019902000PenicillinProntosilCephalosporin CEthambutolFusidic acidMupirocinNalidixic acidOxazolidinonesCecropinFl
3、uoroquinolonesNewer aminoglycosidesSemi-synthetic penicillins&cephalosporinsNewer carbapenemsTrinemsSynthetic approachesEmpiric screeningNewer macrolides&ketolidesRifampicinRifapentineSemi-synthetic glycopeptidesSemi-synthetic streptograminsNeomycinPolymixinStreptomycinThiacetazoneChlortetracyclineG
4、lycylcyclinesMinocyclineChloramphenicol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 青霉素和大环内酯耐药 革兰阴性细菌n肠杆菌科uESBLs-喹诺酮,头孢菌素,青霉素类,氨基糖苷类u碳青霉烯酶（KPC,NDM-1?）-碳青酶烯耐药在中国出现和蔓延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,碳青霉烯类VREMRSAABESBL K.pneumoniaeAntibiotic Control and Infect
5、ion Control:The Two Sides of the Resistance“Coin”Rekha Murthy.Implementation of Strategies to Control Antimicrobial Resistance Chest 2001;119;405-411Control of Antibiotic ResistanceNo simplistic policyHomogenous protocolMixing经验性抗感染治疗的基本原则耐药背景下的个体化治疗理性回归/责任所在经验性抗感染治疗的基本原则 -耐药背景下的个体化治疗合理使用碳青霉烯类药物 -指南
6、VS 临床实践内 容 安 排慢性咳嗽和黄痰-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27-year-old man with acute lymphocytic leukemia.51-year-old man with chronic myelogenous leukemi
7、a.22-year-old woman with adult T-cell leukemia.67-year-old woman with adult T-cell leukemia.61-year-old man with interstitial fibrosis;patient was receiving chlorambucil for chronic lymphocytic leukemia.COPRapid testsWhen available.Gram stain!Start adequate antibiotic coverage(within 1 hour?)Tillou
8、A et al.Am Surg 2004;70:841-4Drain purulent collectionSamplingIncluding invasive procedureswhen needed(BAL)合格标本进行微生物学检查 开始经验性抗感染治疗 目标治疗经验性治疗和目标治疗的统一选择哪种抗菌药物 感染部位的常见病原学 选择能够覆盖病原体的抗感染药物 -抗菌谱/组织穿透性/耐药性/安全性/费用考虑药代动力学/药效动力学考虑病人生理和病理生理状态 高龄/儿童/孕妇/哺乳 肾功不全/肝功不全/肝肾功能联合不全其它因素 杀菌和抑菌/单药和联合/静脉和口服/疗程 经验性抗感染治疗合理选择
9、药物-considerations in choosing antibiotic for empiric therapy 评估病原体 -有的而放矢！评估耐药性 -到位不越位！病情严重性评估+-个体化评估-特殊修正因子 先期抗菌药物对细菌学及其耐药性影响 不同部位感染-病原体的流行病学 从病原学认识感染性疾病MouthPeptococcusPeptostreptococcusActinomycesSkin/Soft TissueS.aureusS.pyogenesS.epidermidisPasteurellaBone and JointS.aureusS.epidermidisStreptoc
10、occiN.gonorrhoeaeGram-negative rodsAbdomenE.coli,ProteusKlebsiellaEnterococcusBacteroides sp.Urinary TractE.coli,ProteusKlebsiellaEnterococcusStaph saprophyticusUpper RespiratoryS.pneumoniaeH.influenzaeM.catarrhalisS.pyogenesLower Respiratory CommunityS.pneumoniaeH.influenzaeK.pneumoniaeLegionella p
11、neumophilaMycoplasma,ChlamydiaLower RespiratoryHospitalK.pneumoniaeP.aeruginosaEnterobacter sp.Serratia sp.S.aureusMeningitisS.pneumoniaeN.meningitidisH.influenzaGroup B StrepE.coliListeria抗菌谱(coverage)组织穿透性(tissue penetration)耐药性(resistance,specifically local resistance)参考代表性资料/依靠当地资料安全性(safety pro
12、file)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择的基本原则评价病原体耐药可能？是否耐药菌？-了解耐药病原体流行状况 参考代表性治疗/依靠当地资料 -个体化用药-合理用药的精髓 病人来源：社区、养老院、医院 高龄、基础疾病、近期抗菌药物、近期住院、侵袭性操作、晚发医院感染 S.aureusPenicillin1944Penicillin-resistantS.aureus金黄色葡萄球菌耐药的发生发展过程Methicillin1962Methicillin-resistantS.aureus(MRSA)Van
13、comycin-resistantenterococci(VRE)Vancomycin1990s1997VancomycinintermediateS.aureus(VISA)2002Vancomycin-resistantS.aureusCDC,MMWR 2002;51(26):565-5671960评价病原体耐药可能？是否耐药菌？-了解耐药病原体流行状况 参考代表性治疗/依靠当地资料 -个体化用药-合理用药的精髓 病人来源：社区、养老院、医院 高龄、基础疾病、近期抗菌药物、近期住院、侵袭性操作、晚发医院感染 01020304050607020012002200320042005200620
14、07200828.645.75954.657.86060.260.225.734.947.736.640.451.53845.7E.coliK.pneumoniae%year细菌耐药监测结果如何解读？Wang H,Chen M.Diagnos Microbiol Infect Dis,2005,51,201-208CMSS/SEANIR/CARES.实验室药物敏感性监测的解读意义-反映了耐药趋势/告诫要谨慎使用抗菌药物 -影响选择药物/考虑耐药性对疗效的影响不足 -实验室收集菌株/大型教学医院/ICU 抗生素选择压力导致耐药性高估！-没有临床背景资料/不能用于指导个体化用药 （年龄、基础疾病、
15、社区/医院感染、前期抗菌药物使用情况）No Risk Factors for MDROsRisk Factors for MDR EnterobacteriaceaeaRisk Factors for MDR PseudomonasHealth care contact No Yes!(eg,recent hospital admission,nursing home,dialysis)without invasive procedure Yes,Long hospitalization and/or infection following invasive procedures(5 days
16、)Recent Abx No Yes!(14 days in past 90 days)Yes!(14 days in past 90 days)对Patient characteristics Young few comorbidities 65 yrs comorbidities such as TPN or renal insufficiency co-morbidities such as CF,structural lung disease,advanced AIDS,neutropenia,or other severe immunodeficiency Drugs of choiceAmoxi/calvAmpicillin/sulb2nd or 3rd GFQsPip/tazoCefaperazone/sulbactamertapenemCeftazidine cefepimePip/tazoCefperazone/sulbactamImipenem meropenemaExcept nonfermenters/non-Pseudomonas species.Adapte
