三种抗阳性菌药物比较.ppt
稳可信VS替考拉宁及利奈唑胺（药物的三大特性比较）l有效性l安全性l经济性稳可信的有效性l 作用机制l 耐药及敏感率l MIC：万古MIC“飘逸”而非“漂移”l 临床疗效l 指南推荐重杀菌机制相对于人工合成抗生素的单一抑菌机制万古霉素让葡萄球菌更无从抵抗1.影响细菌细胞膜的通透性2.抑制细菌细胞壁的合成3.抑制细菌浆内RNA合成123MDRSP=多药耐药菌株,MRSH=溶血性葡萄球菌实用抗感染治疗学第一版 汪复、张婴元主编，第九章 多肽类抗生素：pp281,pp284.稳可信上市 年全球仅出现 株耐药1997年日本首先报告了对万古霉素中度敏感的金黄色葡萄球菌(VISA)12002年07年在北美地区先后共确定9株耐药的金黄色葡萄球菌(VRSA)2我国尚无报道1,Chemother JA,Hiramatsu K,Janaki H.Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility.1997,40:135-1362,Finks J,Wells E,Dyke TL,et al.Vancomycin Resistant Staphylococcus aureus,Michigan USA,2007.Emerging Infectiuos Diseases 2009,15(6):943-945.重杀菌机制赋予万古霉素持久不变的敏感率1.Sanches IS,Mato R,Lencastre HD,et al.Patterns of multidrug resistance among Methicillin Resistant Hospital Isolates of Coagulase-Positive and Coagulase-Negative Staphylococci Colleted in the International Muticenter Study RESIST in 1997 and 1998.Microbial Drug Resistance 2000,6(3):199-211.2.实用抗感染治疗学第一版 汪复、张婴元主编,第九章 多肽类抗生素：pp281,pp284.作用于核糖体单一抑菌机制的利奈唑胺的耐药1999年12000年2001年22005年3三期临床时出现2株LRE利奈唑胺上市出现3株LRSA美国匹兹堡大学医疗中心ICU出现74株LRCNSLRE=耐利奈唑胺肠球菌,LRSA=耐利奈唑胺金葡菌,LRCNS=耐利奈唑胺凝固酶阴性葡萄球菌1.Venikata G,Gold HS.Antimicrobial resistance to Linezolid.Clinical Infectious Diseases 2004,39:1010-1015.2.Tsiodras S,Gold HS,Sakoulas G,et al.Linezolid resistance in a clinical isolate of Staphylococcus aureus.Lancet 2001,358:207-208.3.Poloski BA,Adams J,Clarke L,et al.Epidemiological Profile of Linezolid-Resistant Coagulase-Negative Staphylocucci.Clinical Infectious Diseases 2006,43:165-171.所有金葡菌对万古霉素仍保持100%敏感率2007年ZAAPS细菌耐药性监测结果Jones RN,Kohno S,Ono Y,et al.ZAAPS International Surveillance Program(2007)for Linezolid resistance:results from 5591 Gram-Positive clinical isolates in 23 countries.Diagnostic Microbiology and Infectious Disease 2009,64:191-201.敏感率%国内葡萄球菌对万古霉素保持 敏感率2008年中国CHINET细菌耐药性监测结果(n=3525)(n=2313)耐药金葡菌敏感率(%)汪复,朱德妹,胡付品等.2008年中国CHINET细菌耐药性监测.中国感染与化疗杂志 2009,9(5):321-329.国内葡萄球菌对万古霉素保持 敏感率全国主要抗生素对葡萄球菌属敏感率监测(Mohnarin)2008(n=10409)(n=5981)肖永红，王 进，赵彩云等，20062007年Mohnarin细菌耐药监测,中华医院感染学杂志2008,18(8):1051-1056利奈唑胺目前的MIC分布情况图220004008001200160020000.120.250.51248利奈唑胺MIC(g/ml)株数(N)6株4株2007年ZAAPS细菌耐药性监测结果1万古霉素对于金葡菌的MIC90仅为1mg/LJones RN,Kohno S,Ono Y,et al.ZAAPS International Surveillance Program(2007)for Linezolid resistance:results from 5591 Gram-Positive clinical isolates in 23 countries.Diagnostic Microbiology and Infectious Disease 2009,64:191-201.11欧洲43家医院监测结果Bacteria Year Strain NoVancomycin Teicoplanin MICrMIC90MICrMIC90S.aureus20053370.25-210.12-8220062200.5-210.25-4120071310.5-210.25-412008690.25-210.25-41CoNS2005933282007810.5-220.25-842008910.25-220.12-84S.pyogenes 2005410.250.25NtNt 2006-20071460.12-0.50.250.03-40.032008540.12-0.250.250.03-112820.25-1280.25ECCMID 2009,p1620ECCMID 2009,163713万古霉素和利奈唑胺治疗院内肺炎疗效相当在利奈唑胺提交给FDA的临床报告中详细描述了治疗医院内肺炎的临床研究.该研究用万古霉素和利奈唑胺进行对照显示万古霉素可评价临床疗效为60%，利奈唑胺可评价临床疗效57%，二者疗效相当，利奈唑胺疗效并未超越万古霉素。0 01010202030304040505060利奈唑胺利奈唑胺万古霉素万古霉素利奈唑胺利奈唑胺万古霉素万古霉素ZYVOX 产品说明书信息 Distributed by Pfizer Pharmacia&Upjohn Company Divison of Pfizer Inc,NY,NY10017 LAB-0319-16.0%linezolid versus Vancomycin or Teicoplanin for Nosocomial Pneumonia:A Meta-Analysis AC.KALIL,M.H.MURTHY,E.HERMSEN,et al.Methods:Prospective,randomized trials which tested linezolid vs.vancomycin or teicoplanin for treatment of NP were included.Heterogeneity was analyzed by I2 and Q statistics.Relative Risks(RR)were based on the Mantel-Haenszel method.Outcomes analyzed included clinical cure(CC),microbiologic eradication(ME),and side effects.Results:8 linezolid trials(6 vancomycin,2 teicoplanin)were included(N=853).The linezolid vs glycopeptide analysis shows:CC RR=1.01(95%CI 0.93,1.10,p=0.80;I2=0%;N=853);ME RR=1.10(CI 0.97,1.23;p=0.11;I2=0%;N=597);and MRSA population RR=1.14(CI 0.82,1.58;p=0.44;I2=47%;N=191).If linezolid is compared to vancomycin only,the CC RR remains 1.01(CI 0.90,1.12),and ME and MRSA RRs are:1.06(CI 0.88,1.28)and 1.04(CI 0.73,1.47),respectively.The risk of thrombocytopenia(RR=1.92 CI 1.29,2.86;p=0.001)and GI events(RR=1.90 CI 1.04,3.48;p=0.03)were significantly higher with linezolid,but no differences were seen for renal dysfunction(RR=0.82 CI 0.52,1.27;p=0.37),or all-cause deaths(RR=0.95 CI 0.76,1.18;p=0.63).Conclusions:Meta-analysis did not detect clinical superiority of linezolid vs.glycopeptides for treatment of NP.Compared to linezolid,vancomycin was not associated with more renal dysfunction.linezolid showed a significant increase in the risk of thrombocytopenia and GI events.Available data does not support the claim that linezolid is superior to vancomycin for the treatment of NP.万古霉素治疗MRSA感染疗效未被超越包括菌血症、肺炎以及皮肤软组织感染万古霉素1g/次，每天2次7-28天(n=220),利奈唑胺600mg/次，每天2次7-28天(n=240)Stevens DL,Herr D,Lampiris H,et al.Linezolid versus Vancomycin for the Treatment of Methicillin Resistant Staphylococcus aureus Infections.Clinical Infectious Diseases 2002,34:1481-1490.万古霉素治疗MRSA起效时间未被超越万古霉素1g q12h，7-21天(n=61),利奈唑胺600mg q12h，7-21天(n=57),*退热定义为体温完全恢复正常时间(天)P=0.2057P=0.1760P=0.6149Http:/www.clinicalstudyresults.org/doc
