万古霉素-稳可信说课讲解课件.ppt
稳可信团队销售幻灯通用篇,Vancocinpro20101211,MRS在全世界快速蔓延,Vancocinpro20101211,汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志 2010;10(5):325-334.,2009中国CHINET2MRSA-52.7%MRCNS-71.7%,MRSA肆虐中国大陆:CHINET 2009,汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志 2010;10(5):325-334.,MRSA各大医院检出率,Michael D.Nailor,Jack D.Sobel.Antibiotics for Gram-Positive Bacterial Infections:Vancomycin,Teicoplanin,Quinupristin,Oxazolidinones,Daptomycin,Dalbavancin,and Telavancin.Infect Dis Clin N Am,2009,23:965-982,三重杀菌机制是万古霉素持久敏感的基础,2007年ZAAPS研究万古霉素 vs.替考拉宁 vs.利奈唑胺的敏感率,敏感率,Jones RN,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;64:191201.,金黄色葡萄球菌,CHINET 2009万古霉素对MRSA与MRCNS保持100%敏感,Vancocinpro20101211,汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志 2010;10(5):325-334.,CHINET 2009:2167株MRSA耐药率,汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志 2010;10(5):325-334.,CHINET 2009:1967株MRCNS耐药率,汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志 2010;10(5):325-334.,英国与爱尔兰 2001-2007MRSA对万古霉素MIC值稳定,“采用历史数据去检测细微的MIC漂移是会被误导的”Prof.Reynolds presented at ICAAC 2009.,Reynolds R,et al.The Illusion of MIC Creep in MRSA.ICAAC 2009;12-145.,中国 2005-2008金葡菌对万古霉素的MIC值稳定,王辉.北京协和医院.GPRS资料.,万古霉素:抑制细胞壁的合成1,万古霉素:影响细胞膜的通透性1,万古霉素:抑制细菌浆内RNA合成1,50,50,50,30,30,核糖体(mRNA),THFA(四氢叶酸),DHFA(二氢叶酸),细菌细胞,30,1.实用抗感染治疗学主审 戴自英.主编 汪复 张婴元.人民卫生出版社2004年11月第1版.第二篇 第十一章 其他抗菌药物:P400.2.夏梦岩等.细菌对利奈唑胺的耐药机制及检测方法研究进展.微生物与感染 2009;4(3):170-173.3.李娟.利奈唑胺及其耐药机制研究进展.西部医学 2009;21(4):667-668.,单一抑菌机制导致利奈唑胺耐药事件频发,2010年CLSI公布了利奈唑胺耐药折点标准,利奈唑胺耐药金葡菌达到 0.05%,报告时无须复杂的确认流程,新!,Mendes,et al.First Report of cfr-Mediated Resistance to Linezolid in Human Staphylococcal Clinical Isolates Recovered in the United States.Antimicrob。Agents Chemother 2008;52(6):2244-2246.,1999年:三期临床时出现2株LRE1,2000年:利奈唑胺上市,1.Meka VG,et al.Antimicrobial Resistance to Linezolid.Clinical Infectious Diseases 2004,39:1010-1015.2.Pillai SK,et al.Linezolid Resistance in Staphylococcus aureus:Characterization and Stability of Resistant Phenotype.JID 2002;186:1603-1607.3.Potoski BA,et al.Epidemiological Profile of Linezolid-Resistant Coagulase-Negative Staphylococci.Clinical Infectious Diseases 2006,43:165-171.4.Kelly S,et al.An outbreak of colonization with linezolid-resistant Staphylococcus epidermidis in an intensive therapy unit.Journal of Antimicrobial Chemotherapy 2008;61:901907.5.Ikeda-Dantsuji Y,et al.Linezolid-resistant Staphylococcus aureus isolated from 2006 through 2008 at six hospitals in Japan.J Infect Chemother,published online 2010.6.Sanchez Garca M,et al.Clinical Outbreak of Linezolid-Resistant Staphylococcus aureus in an Intensive Care Unit.JAMA 2010;303(22):2260-2264.7.Mazzariol A,et al.Linezolid resistance in a Staphylococcus haemolyticus strain isolated in an intensive care unit.17th ECCMID/25th ICC,Posters P890.8.Rodriguez-Aranda A,et al.Nosocomial spread of linezolid-resistant Staphylococcus haemolyticus infections in an intensive care unit.Diagnostic Microbiology and Infectious Disease 2009;63:398-402.9.Gales AC,et al.Emergence of linezolid-resistant Staphylococcus aureus during treatment of pulmonary infection in a patient with cystic fibrosis.International Journal of Antimicrobial Agents 2006;27:300-302.10.Hentschke M,et al.Emergence of Linezolid Resistance in a Methicillin Resistant Staphylococcus aureus Strain.Infection 2008;36(1):85-87.11.Calvo J,et al.Linezolid resistance in clinical isolates of Staphylococcus haemolyticus.17th ECCMID/25th ICC,Posters P887.12.Kosowska-Shick K,et al.Diagnostic Microbiology and Infectious Disease 2010;68:34-39.13.Tsiodras S,et al.Linezolid resistance in a clinical isolate of Staphylococcus aureus.Lancet 2001;358:207-208.,2005年(美国):74株LRCNS3,2006年(爱尔兰):16例LRSE4,2006-2008年(日本)13株LRSA5,2008年(西班牙):12例LRSA,6例死亡6,2002年(美国):5株LRSA2,2006年(意大利):1例LRSH7,2005年(德国):1例LRSA10,2005-2007年(西班牙):15例LRSH8,2006年(巴西):1例LRSA9,2006年(西班牙):4株LRSH11,2007年(美国):17例LRCNS12,LRSH=耐利奈唑胺溶血性葡萄球菌,LRSA=耐利奈唑胺金葡菌,LRCNS=耐利奈唑胺凝固酶阴性葡萄球菌,LRSE=耐利奈唑胺表皮葡萄球菌,2001年(美国):3株LRSA13,单一抑菌机制导致利奈唑胺耐药事件频发,抗生素的耐药发展史,新药迅速耐药值得重视,万古霉素从上市到耐药出现经历了44年,利奈唑胺问世后1年就出现耐药,Clatworthy AE,et al.Targeting virulence:a new paradigm for antimicrobial therapy.Nature chemical biology 2007;3(9):541-548.,2008年中国浙江省数据耐利奈唑胺的金葡菌发生率可达1.0%,浙江省医院细菌耐药监测年鉴(2008年版).P23.,2008年中国浙江省数据耐利奈唑胺的表葡菌发生率可达1.3%,浙江省医院细菌耐药监测年鉴(2008年版).P23.,万古霉素单药治疗LRSA效果良好,耐利奈唑胺患者(n=12),存活率100%,Snchez Garca M,et al.Clinical Outbreak of Linezolid-Resistant Staphylococcus aureus in an Intensive Care Unit.JAMA 2010;303(22):2260-2264.,减少利奈唑胺用量可以有效减少LRSA,Snchez Garca M,et al.Clinical Outbreak of Linezolid-Resistant Staphylococcus aureus in an Intensive Care Unit.JAMA 2010;303(22):2260-2264.,发生12例LRSA,其中6例死亡,未发生LRSA,稳可信拥有广泛的适应症,稳可信:拥有广泛的适应症,1.万古霉素产品说明书,2.利奈唑胺产品说明书,3.替考拉宁产品说明书,CRBSI:导管相关血流感染,利奈唑胺受到美国FDA的警告1,2007年FDA向医生发出警告治疗导管相关感染的研究表明2利奈唑胺治疗首次用药后84天内的死亡率21.5%(78/363),而对照组为16.6%(58/363)。,1,Wilcox MH,Tack KJ,Bouza E,et al.Complicated skin and skin structure infections and Catheter Related Bloodstream Infections Noninferiority of Linezolid in Phase 3 Sutdy.Clinical Infectious Disease 2009,48:203-212.2,FDA Alert 3/18/2007.,众多权威指南推荐稳可信为治疗MRS的首选,桑福德抗微生物治疗指南(20102011版)美国胸科协会(ATS)关于医院获得性、呼吸机相关及医疗相关肺炎治疗指南(2005版)美国抗感染协会(IDSA)关于导管相关感染(2009版)皮肤软组织感染治疗指南(2005版)HAP亚洲工作组关于HAP组首次共识欧洲心脏协会(ESC)关于感染性心内膜炎的预防、诊断及治疗指南(2003版)英国抗菌化疗协会(BSAC)关于MRSA感染预防和治疗指南(2006版)新英格兰杂志关于脑膜炎感染预防和治疗指南(2010版),万古霉素是治疗MRS感染的首选,随着万古霉素的纯度提高,肾毒性发生率大大减少,1.Rybak M,et al.Therapeutic monitoring of vancomycin in adult patients:A consensus review of the American Society of Health-System Pharmacists,the Infectious Diseases Society of America,and the Society of Infectious Diseases Pharmacists.Am J Health-Syst Pharm 2009;66:82-98.2.林东昉等.利奈唑胺与万古霉素治疗革兰阳性菌感染的随机、双盲、对照、多中心临床试验.中国感染与化疗杂志 2009;9(1):10-17.3.Stevens DL,et al.Linezolid versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections.Clinical Infectious Diseases 2002;34:1481-90.4.Abad F,et al.Comparative pharmacoeconomic study of vancomycin and teicoplanin in intensive care patients.International Journal of Antimicrobial Agents.International Journal of Antimicrobial Agents 2000;15:65-71.5.Downs NJ,et al.Mild Nephrotoxicity Associated With Vancomycin Use.6.Sorrell TC,et al.PJ.A prospective study of adverse reactions associated with vancomycin therapy.J Antimicrob Chemother 1985;16(2):235-41.7.Farber BF,et al.Retrospective Study of the Toxicity of Preparations of Vancomycin from 1974 to 1981.Antimicrobial agents and chemotherapy 1983;23(1):138-141.8.Levine DP.Vancomycin:A History.Clinical Infectious Diseases 2006;42:S5-12.,治疗MRSA感染万古霉素的肾脏安全性与利奈唑胺无显著差异,Stevens DL,et al.Linezolid versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections.Clinical Infectious Diseases 2002;34:1481-1490.,治疗革兰氏阳性菌感染万古霉素的肾毒性不高于利奈唑胺,发生率(%),林东昉等.利奈唑胺与万古霉素治疗革兰阳性菌感染的随机、双盲、对照、多中心临床试验.中国感染与化疗杂志 2009;9(1):10-17.,2009年辉瑞中国上市临床研究,血小板减少的危害,血小板减少程度是预测重症患者死亡的独立危险因子,入住ICU的时间(天),生存率,Moreau D,et al.Platelet count decline:an early prognostic marker in critically ill patients with prolonged ICU stays.CHEST 2007;131:17351741.,血小板计数下降60%,血小板下降达到30%是预示患者死亡的独立危险因素,其死亡是血小板正常患者的1.54倍(95 Cl:1.122.14,p=0.008),血小板减少发生风险利奈唑胺的远大于糖肽类,2项荟萃分析,1.对于革兰氏阳性菌利奈唑胺引起血小板减少的发生概率是糖肽类或-内酰胺的11.72倍,2.对于院内感染利奈唑胺引起血小板减少的发生概率是糖肽类的1.93倍,1.Falagas ME,et al.Linezolid versus glycopeptide or-lactam for treatment of Gram-positive bacterial infections:meta-analysis of randomised controlled trials.Lancet Infect Dis 2008;8(1):53-66.2.Kalil A.C,et al.Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia:A systematic review and meta-analysis.Crit Care Med 2010;38(9):1-7.,谢谢关注!,