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1、替考拉宁治疗 MRSA 肺部感染的优势,检出率%,2009年 CHINET 43670 株临床分离株中前十位细菌,2009-CHINET资料,我国CHINET耐药监测显示葡萄球菌耐药率较高,Fu Wang et al.Chin J Infect Chemother 2009;9(5):321-329.,金黄色葡萄球菌及凝固酶阴性葡萄球菌中甲氧西林耐药菌株比例分别为 55.7%和 75.9%,11052 株 G+菌菌株,亚洲国家HAP病原学研究提示金葡菌是主要致病菌,Asian HAP Working Group.Am J Infect Control 2008;36:S83-92.,VISA,
2、VISA,VISA,VRSA,VRSA,VRSA,MRSA,VSSA,VSSA,VSSA,1999年1,2000年,2001年2,2005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LRCNS,LRSA（耐利奈唑胺金葡菌）出现情况,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 r
3、esistance 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 2006,43:165-171.4.An outbreak of colonization with linezolid-resistant Sta
4、phylococcus epidermidis in an intensive therapy unitKelly S,Collins J,Maguire M.Journal of Antimicrobial Chemotherapy,2008,61,9019075.Yurika Ikeda-Dantsuji Hideaki Hanaki Fuminori Sakai,et al.Linezolid-resistant Staphylococcus aureus isolated from 2006 through 2008 at six hospitals in Japan,J Infect
5、 Chemother,published online:07 july 2010.6.Snchez Garca M,De la Torre MA,Morales G,Clinical Outbreak of Linezolid-Resistant Staphylococcus aureus in an Intensive Care Unit.JAMA.2010 Jun 9;303(22):2260-4.,2006年4,200608年5,爱尔兰一医院ICU 出现16株LRSE,日本上市后两年内连续出现13株LRSA,2008年6,西班牙一ICU出现15 株LRSA，其中6例患者 死亡,作用于核糖
6、体单一抑菌机制的利奈唑胺的耐药,Vancomycin、Linezolid MIC creep,Journal of Antimicrobial Chemotherapy(2007)60,788794,Clatworthy AE,Pierson E,Hung DT,et al.Targeting virulence:a new paradigm for antimicrobial therapy.Nature chemical biology.2007,3(9):541-548,抗生素的耐药发展史，新药迅速耐药值得重视,MRSA 病原药物之肺穿透比較,万古霉素治疗 MRSA 肺炎失败率高,治疗成
7、功率(%),Moise,DeRyke,ClinEval,lIT,Wunderink,N=35,N=42,N=18,N=20,N=54,Fagon,万古霉素治疗MRSA所致呼吸机相关肺炎失败率高,Wunderink RG.Sem Respir Criti Care Med.2006;27:92-103,替考拉宁,万古霉素的结构升级,万古霉素,替考拉宁,糖基修饰,脂肪酸侧链,分子量：1486,分子量：1891,替考拉宁应运而生,抗耐药阳性菌药物的组织穿透比较,30%的金葡感染必須考慮 metastatic infection，不適合使用 vancomycin Teicoplanin 組織穿透力強，
8、對metastatic infection之治療優於vancomycin,European Glycopeptide Susceptibility Survey 2008,分离株%,MIC分布MRSA（n2852）,European Glycopeptide Susceptibility Survey 1995,MIC分布肠球菌属（n1695）,分离株%,替考拉宁良好的体外抗菌活性,对金葡菌的抗菌活性比万古霉素强 24 倍对凝固酶阴性葡萄球菌的作用与万古霉素相仿对链球菌(包括肺炎链球菌)的抗菌活性优于万古霉素对肠球菌的抗菌活性比万古霉素强 48 倍耐万古霉素的 VanB,VanC 等 VRE
9、对本品仍敏感,糖肽类目标浓度,对13例 SICU 内 MRSA-VAP 应用 Teicoplanin 12mg/kg 30min IV q12h 2d,此后12mg/kg gd 4-6d 同时测定血清和FLE药物浓度结果：血清谷浓度中位数:15.9g/ml(8.9-29.9g/ml)FLE浓度中位数：4.9g/ml（2.0-11.8g/ml）结论：为达到稳态时肺组织中足够的药物谷浓度，在合并VAP的危重患者 应用替考拉宁 12mg/kg 30min IV q12h 2d,此后12mg/kg gd 其肺组织浓度均可保证2g/ml,Intensive Care Med 2006,32:776-77
10、9,Steady-state trough serum and epithelial lining fluid concentrations of teicoplanin 12 mg/kg per day in patients with ventilator-associated pneumonia.,替考拉宁与万古霉素的药代动力学比较,给药途径,弥散速度,血浆蛋白结合率,替考拉(6mg)/kg,万古霉素500mg,指标,Clinical Efficacy and Renal Toxicity among Patients with Febrile Neutropenia Teicoplan
11、in Vs.Vancomycin,Retrospective,comparative,single-center study100 consecutive neutropenic patients with hematological malignancies and persistent fever after 72 hours of first-line antibiotic therapyGroup T:50 patients from 8/1996 to 9/2000 received teicoplanin+piperacillin/tazobactam and gentamicin
12、Group V:50 patients from 10/2000 to 4/2002 received vancomycin+meropenem and levofloxacin,Hahn-Ast C et al.Infection 2008;36:548.,Definition of Treatment SuccessSuccess of empirical antimicrobial therapy was defined as defervescence for at least 7 days in absence of any sign of continuing infection.
13、Patients who were still febrile at day 21 of antimicrobial treatment were classified as failures.Definition of NephrotoxicityDocumented by monitoring of serum creatinineIncrease of 0.5 mg/dlDoubling of creatinine,Hahn-Ast C et al.Infection 2008;36:548.,Hahn-Ast C et al.Infection 2008;36:548.,Vancomy
14、cin Teicoplanin,-64%,p0.05,Hahn-Ast C et al.Infection 2008;36:548.,替考拉宁治疗 1431 例病人的不良事件,J Antimicrob Chemother 1988 Jan;21 Suppl A:61-7,Wilcox et al.J Antimicrob Chemother 2004;53:335344,临床治愈率,利奈唑胺与替考拉宁,C.Tascini.et.al.Journal of Chemotherapy.2009;21:311-316.,利奈唑胺与替考拉宁治疗G+菌感染的回顾性研究,研究简介,研究目的：比较利奈唑胺与
15、替考拉宁治疗 G+菌感染的疗效、不良反应、患者生存率及住院时间等研究方式：回顾性对照研究入选人群：169 例使用利奈唑胺的患者，91 例使用替考拉宁的患者,C.Tascini.et al.Journal of Chemotherapy.2009;21:311-316.,患者特征,*：p0.007；：p0.002,C.Tascini.et al.Journal of Chemotherapy.2009;21:311-316.,菌血症及肺炎是两组患者最常见的感染类型,C.Tascini.et al.Journal of Chemotherapy.2009;21:311-316.,临床有效率(%),
16、32/37,12/15,15/22,7/10,15/16,11/14,13/16,9/14,13/14,8/13,10/14,利奈唑胺治疗各部位感染的临床有效率与替考拉宁无统计学差异,C.Tascini.et al.Journal of Chemotherapy.2009;21:311-316.,研究结果,P0.002,P0.05,不良反应发生率比较,结果显示：利奈唑胺组患者的不良反应发生率略高于替考拉宁组,C.Tascini.et al.Journal of Chemotherapy.2009;21:311-316.,两组死亡率比较,患者死亡率(%),27/169,10/91,结果显示：利奈唑胺组的总体死亡率略高于替考拉宁组,C.Tascini.et al.Journal of Chemotherapy.2009;21:311-316.,Comparison of Anti-MRSA Agents,MRSA 在肺部感染中占有重要地位 有效的治疗药物非常有限，新药产生的耐药状态令人担忧 糖肽类对金葡菌的耐药发展极其缓慢、长期保持其敏感 替考拉宁(他格适）保持万古霉素的抗菌活性，在 PK/PD 得到优化，肺组织等浓度提高，不良反应减少，疗效基本等同于利奈唑胺替考拉宁(他格适）为细菌性脑膜炎治疗的可选药物之一,小 结,
