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1、-谈耐药背景下的个体化抗感染治疗,感染病患者多重耐药菌感染风险的分层 Stratification of Infectious Disease Patients at Risk for MDR Organisms,武汉科技大学附属孝感市中心医院呼吸内科 彭春燕2016年3月9日,抗感染药物发展简史,1929 Alexander Fleming 发现青霉素,Howard Florey 和 Ernst Chain分离获得青霉素，用于动物试验。,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, dramatic
2、ally showing the virtues of the new miracle drug, and representing the high level of motivation in the country to aid the health of the soldiers at war.,Discovery of Antibacterial Agents,Cycloserine Erythromycin Ethionamide Isoniazid Metronidazole Pyrazinamide Rifamycin Trimethoprim Vancomycin Virgi
3、niamycin,Imipenem,1930,1940,1950,1960,1970,1980,1990,2000,Penicillin Prontosil,Cephalosporin C,Ethambutol Fusidic acidMupirocin Nalidixic acid,Oxazolidinones Cecropin,Fluoroquinolones,Newer aminoglycosides,Semi-synthetic penicillins & cephalosporins,Newer carbapenems,Trinems,Synthetic approaches,Emp
4、iric screening,Newer macrolides & ketolides,Rifampicin,Rifapentine,Semi-synthetic glycopeptides Semi-synthetic streptogramins,Neomycin Polymixin Streptomycin Thiacetazone,Chlortetracycline,Glycylcyclines,Minocycline,Chloramphenicol,临床关注的耐药问题 Resistances of Clinical Concerns,革兰阳性细菌 金匍菌 MRSA, VISA, VR
5、SA VRE (地理上差别) 肺炎链球菌 青霉素和大环内酯耐药 革兰阴性细菌 肠杆菌科 ESBLs-喹诺酮,头孢菌素,青霉素类,氨基糖苷类 碳青霉烯酶（KPC, NDM-1?）-碳青酶烯耐药在中国出现和蔓延 非发酵菌(假单孢菌/不动杆菌) 喹诺酮, 头孢菌素,青霉素类,氨基糖苷,碳青霉烯类,Antibiotic Control and Infection Control: The Two Sides of the Resistance “Coin”,Rekha Murthy. Implementation of Strategies to Control Antimicrobial Resis
6、tance Chest 2001;119;405-411,Control of Antibiotic Resistance,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,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-y
7、ear-old man with acute lymphocytic leukemia.,51-year-old man with chronic myelogenous 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.
8、,COP,Rapid tests When available. Gram stain!,Start adequate antibiotic coverage (within 1 hour?) Tillou A et al. Am Surg 2004;70:841-4,Drain purulent collection,Sampling 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
9、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,SSSS,PCP,抗菌谱(coverage) 组织穿透性(tissue
10、 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 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. aureus,Penicillin,1944,Peni
11、cillin-resistant S. aureus,金黄色葡萄球菌耐药的发生发展过程,Methicillin,1962,Methicillin-resistant S. aureus (MRSA),Vancomycin-resistant enterococci (VRE),Vancomycin,1990s,1997,Vancomycin intermediate S. aureus (VISA),2002,Vancomycin- resistant S. aureus,CDC, MMWR 2002;51(26):565-567,1960,评价病原体耐药可能？,是否耐药菌？-了解耐药病原体流
12、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,中国大陆ESBL的发生率,%,Wang H, Chen M. Diagnos Microbiol Infect Dis, 2005, 51, 201-208CMSS/SEANIR/CARES.,year,细菌耐药监测结果如何解读？,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
13、于指导个体化用药(年龄、基础疾病、社区/医院感染、前期抗菌药物使用情况),aExcept nonfermenters/non-Pseudomonas species. Adapted from Carmeli Y. Predictive factors for multidrug-resistant organisms. In: Role of Ertapenem in the Era of Antimicrobial Resistance newsletter. Available at: www.invanz.co.il/secure/downloads/IVZ_Carmeli_NL_20
14、06_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):17921798; Shah PM. Clin Microbiol Infect. 2008;14(suppl 1):175180.,Stratification for Risk for
15、MDR Gram-Negative Pathogens,重症感染耐药菌感染！ 重症感染革兰阴性肠杆菌科细菌感染！ 肺炎链球菌、化脓性链球菌、军团菌、肺孢子菌等均可致重症感染,PCP,LD,对于选择抗菌药物-耐药性 VS 严重性哪个更重要？,PCP,LD,耐药菌感染 VS 严重感染 -PCP和LD告诉我们什么？,观点:-耐药性判断对于合理选择抗菌药物更重要！包括重症感染-即使重症感染,抗感染治疗方案仍需根据病原体及其耐药性评估来制定,经验性抗感染治疗的基本原则 耐药背景下的个体化治疗 以CAP/HAP为例,22,Craven DE. Curr Opin Infect Dis. 2006;19:1
16、53-160.,The Changing Spectrum of Pneumonia CAP, HCAP, HAP,“Healthcare-associated pneumonia is a relatively new clinical entity that includes a spectrum of adult pts who have a close association with acute-care hospitals or reside in chronic-care settings that increase their risk for pneumonia caused by MDR pathogens.“,a. CAP=community-acquired pneumonia b. HCAP=healthcare-associated pneumonia c. HAP=hospital-acquired pneumonia d. VAP=ventilator-associated pneumonia,
