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1、陈陈 佰佰 义义 感染病患者多重耐药菌感染风险的分层感染病患者多重耐药菌感染风险的分层 谈耐药背景下的个体化抗感染治疗谈耐药背景下的个体化抗感染治疗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 representi
2、ng the high level of motivation in the country to aid the health of the soldiers at war.Discovery of Antibacterial AgentsCycloserine Erythromycin Ethionamide Isoniazid Metronidazole Pyrazinamide Rifamycin Trimethoprim Vancomycin VirginiamycinImipenem19301940 195019601970198019902000Penicillin Pronto
3、silCephalosporin CEthambutol Fusidic acidMupirocin Nalidixic acidOxazolidinones CecropinFluoroquinolonesNewer aminoglycosidesSemi-synthetic penicillins 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
4、理使用碳青霉烯类药物-指南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 myeloge
5、nous leukemia. 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 tests When available. Gram stain! Start adequate antibiotic coverage (wi
6、thin 1 hour?) Tillou A et al. Am Surg 2004;70:841-4Drain purulent collectionSampling Including invasive procedures when 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
7、服/疗程经验性抗感染治疗合理选择药物 -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Mouth Peptococcus Peptostreptococcus ActinomycesSkin/Soft Tissue S. aureus S. pyogenes S. epidermidis PasteurellaBone and Joint S.
8、aureus S. epidermidis Streptococci N. gonorrhoeae Gram-negative rods Abdomen E. coli, Proteus Klebsiella Enterococcus Bacteroides sp.Urinary Tract E. coli, Proteus Klebsiella Enterococcus Staph saprophyticusUpper Respiratory S. pneumoniae H. influenzae M. catarrhalis S. pyogenesLower Respiratory Com
9、munity S. pneumoniae H. influenzae K. pneumoniae Legionella pneumophila Mycoplasma, ChlamydiaLower Respiratory Hospital K. pneumoniae P. aeruginosa Enterobacter sp. Serratia sp. S. aureusMeningitis S. pneumoniae N. meningitidis H. influenza Group B Strep E. coli Listeria抗菌谱(coverage)组织穿透性(tissue pen
10、etration)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-resista
11、nt S. aureus金黄色葡萄球菌耐药的发生发展过程Methicillin1962Methicillin-resistant S. aureus (MRSA)Vancomycin-resistant enterococci (VRE)Vancomycin1990s1997Vancomycin intermediate S. aureus (VISA)2002Vancomycin- resistant S. 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
12、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、晚发医院感染中国大陆中国大陆ESBLESBL的发生率的发生率 %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、社区/医院感
13、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 day
14、s) Recent Abx No Yes! (14 days in past 90 days) Yes ! (14 days in past 90 days) 对Patient characteristi cs Young few comorbidities65 yrs comorbidities such as TPN or renal insufficiency co-morbidities such as CF, structural lung disease, advanced AIDS, neutropenia, or other severe immunodeficiency Dr
15、ugs of choiceAmoxi/calv Ampicillin/sulb 2nd or 3rd G FQsPip/tazo Cefaperazone/sulbactam ertapenemCeftazidine cefepime Pip/tazo Cefperazone/sulbactam Imipenem meropenemaExcept nonfermenters/non-Pseudomonas species.Adapted from Carmeli Y. Predictive factors for multidrug-resistant organisms. In: Role
16、of Ertapenem in the Era of Antimicrobial Resistance newsletter. Available at: www.invanz.co.il/secure/downloads/IVZ_Carmeli_NL_2006_W-226364-NL.pdf. Accessed 7 April 2008; Dimopoulos G, Falagas ME. Eur Infect Dis. 2007;4951; Ben-Ami R, et al. Clin Infect Dis. 2006;42(7):925934; Pop-Vicas AE, DAgata EMC. Clin Infect Dis. 2005;40(12):17
