替考拉宁与肺炎.ppt
检出率%2009-CHINET资料资料Fu Wang et al.Chin J Infect Chemother 2009;9(5):321-329.亚洲国家亚洲国家HAP病原学研究提示金葡菌是主要致病菌病原学研究提示金葡菌是主要致病菌排序排序 韩国韩国中国中国台湾台湾泰国泰国马来西亚马来西亚菲利宾菲利宾*印度印度巴基斯坦巴基斯坦1P.aerug(23%)P.aeru(18%)P.aeru(21%)A.baum(28%)A.baum(23%)P.aeru(42.1%)A.baum(38%)A.baum(58%)2MRSA(23%)MRSA(16%)A.baum(20%)P.aeru(18%)P.aeru(17.6%)K.pn(26.3%)K.pn(23%)MRSA(18%)3K.pn(11%)A.baum(16%)MRSA(16%)K.pn(7.7%)MRSA(11.8%)A.baum(13.1%)P.aeru(20%)P.aeru(18%)4A.baum(9%)K.pn(14%)K.pn(9%)MRSA(7.6%)S.malto(11.8%)MRSA(5%)5E.cloa(8%)E.cloa(8%)E.coli(3.6%)E.coli(2.8%)K.pn(5.8%)Asian HAP Working Group.Am J Infect Control 2008;36:S83-92.VISAVISAVISAVRSAVRSAVRSAMRSAVSSAVSSAVSSA1999年年12000年年2001年年2 2005年年3三期临三期临床时出床时出现现2株株LRE利奈利奈唑胺唑胺上市上市出现出现3株株LRSA美国美国匹兹堡匹兹堡大学医疗大学医疗中心中心ICU出现出现74株株LRCNSLRSA（耐利奈唑胺金葡菌）出现情况（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 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 2006,43:165-171.4.An outbreak of colonization with linezolid-resistant Staphylococcus 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 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年年4200608年年5爱尔兰爱尔兰一医院一医院ICU 出现出现16株株LRSE日本上市日本上市后两年内后两年内连续出现连续出现13株株LRSA 2008年年6西班牙西班牙一一ICU出出现现15 株株LRSA，其，其中中6例患者例患者 死亡死亡作用于核糖体单一抑菌机制的利奈唑胺的耐药作用于核糖体单一抑菌机制的利奈唑胺的耐药Vancomycin、Linezolid MIC creepJournal of Antimicrobial Chemotherapy(2007)60,788794Clatworthy 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抗生素的耐药发展史，新药迅速耐药值得重视MRSA 病原药物病原药物之肺穿透比較之肺穿透比較%ELF/serumVancomycin11-17Teicoplanin132(48-332)Linezolid450Tigecycline138Daptomycin2万古霉素治疗万古霉素治疗 MRSA 肺炎失败率高肺炎失败率高替考拉宁替考拉宁万古霉素的结构升级万古霉素的结构升级万古霉素万古霉素替考拉宁替考拉宁糖基修饰脂肪酸侧链分子量：1486分子量：1891抗耐药阳性菌药物的组织穿透比较抗耐药阳性菌药物的组织穿透比较组织组织/体液体液万古霉素万古霉素替考拉宁替考拉宁斯沃斯沃骨骨7-13%50-60%60%脑脊液脑脊液0-18%10%70%上皮细胞衬液上皮细胞衬液 11-17%48-332%100450%炎性渗出液炎性渗出液-77%104%肌肉肌肉30%40%94%腹透液腹透液20%40%61%汗液汗液-55%30%的金葡感染必須考慮的金葡感染必須考慮 metastatic infection，不，不適合使用適合使用 vancomycin Teicoplanin 組織穿透力強組織穿透力強，對對metastatic infection之治療優於之治療優於vancomycinEuropean Glycopeptide Susceptibility Survey 2008分离株%MIC分布分布MRSA（n2852）European Glycopeptide Susceptibility Survey 1995MIC分布肠球菌属（分布肠球菌属（n1695）分离株%替考拉宁良好的体外抗菌活性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对金葡菌的抗菌活性比万古霉素强 24 倍倍对凝固酶阴性葡萄球菌的作用与万古霉素相仿对凝固酶阴性葡萄球菌的作用与万古霉素相仿对链球菌对链球菌(包括肺炎链球菌包括肺炎链球菌)的抗菌活性优于万古霉素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对肠球菌的抗菌活性比万古霉素强 48 倍倍耐万古霉素的耐万古霉素的 VanB,VanC 等等 VRE 对本品仍敏感对本品仍敏感药物药物峰浓度峰浓度谷浓度谷浓度ACU24h万古霉素万古霉素2535 mg/L510 mg/L400 mg/L x h-1替考拉宁替考拉宁4050 mg/L1520 mg/L560 mg/L x h-1糖肽类目标浓度糖肽类目标浓度 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/mlIntensive Care Med 2006,32:776-779Steady-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替考拉宁与万古霉素的药代动力学比较 给药途径给药途径弥散速度弥散速度血浆蛋白结合率血浆蛋白结合率替考拉替考拉(6mg)/kg(6mg)/kg万古霉素万古霉素500mg500mg指标指标Teicoplanin Vs.VancomycinRetrospective,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 gentamicinGroup V:50 patients from 10/2000 to 4/2002 received vancomycin+meropenem and levofloxacinHahn-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.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 creatinineHahn-Ast C et al.Infection 2008;36:548.Hahn-Ast C et al.Infection 2008;36:548.Vancomycin Teicoplanin -64%p0.05Hahn-Ast C et al.Infection 2008;36:548.替考拉宁治疗替考拉宁治疗 1431 例病人的不良事件例病人的不良事件不良事件不良事件例数（例数（%）注射局部反应注射局部反应41（2.9%）非特异性事件非特异性事件73（5.1%）过敏反应过敏反应72（5.0%）血液化验指标异常血液化验指标异常31（2.2%）生化指标异常生化指标异常67（4.7%）耳毒性耳毒性4（0.3%）肾毒性肾毒性5（0.35%）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利奈唑胺与替考拉宁C.Tascini.et.al.J
