抗菌治疗进展精选课件.ppt

关于抗菌治疗进展第一页，本课件共有61页2OUTLINEoMRSA的临床重要性的临床重要性oMRSA的药物敏感性及变迁的药物敏感性及变迁oMRSA感染的抗菌治疗感染的抗菌治疗第二页，本课件共有61页问题1、MRSA的临床重要性如何？o耐药革兰阴性菌给临床带来的问题较革兰阳耐药革兰阴性菌给临床带来的问题较革兰阳性菌更大，如鲍曼不动杆菌性菌更大，如鲍曼不动杆菌o革兰阳性菌中，革兰阳性菌中，MRSAMRSA的临床重要性最大的临床重要性最大第三页，本课件共有61页3.2 million bacterial isolates from 300 clinical lab 19982005 across the United StatesStyers D,et al.Ann Clin Microbiol Antimicrob 2006,5:2.Staphylococcus aureusEscherichia coliEnterococcus spp.Coagulase-negative staphylococciPseudomonas aeruginosaKlebsiella pneumoniaeProteus mirabilisEnterobacter cloacaeSerratia marcescensAcinetobacter baumanniEscherichia coliStaphylococcus aureusEnterococcus spp.Pseudomonas aeruginosaCoagulase-negative staphylococciKlebsiella pneumoniaeProteus mirabilisEnterobacter cloacaeStreptococcus pneumoniaeCitrobacter freundiiPercentage of all bacterial isolates encounteredPercentage of all bacterial isolates encounteredTop ten pathogens among inpatientsTop ten pathogens among outpatients1.51.62.93.16.110.312.712.717.318.805101520253035401.01.01.54.26.26.36.58.814.938.60510152025303540S.aureus is a leading cause of bacterial infections in hospitals and community in the US第四页，本课件共有61页中国革兰阳性菌菌种分布 细菌细菌株数株数 金葡菌金葡菌600035.6 肠球菌属肠球菌属459327.2 凝固酶阴性葡萄球菌凝固酶阴性葡萄球菌335319.9 （血液脑脊液等无菌体液）（血液脑脊液等无菌体液）肺炎链球菌肺炎链球菌11246.7 -溶血性链球菌溶血性链球菌12297.3 草绿色链球菌（血液及无菌体液）草绿色链球菌（血液及无菌体液）2081.2 其他其他3652.2 合计合计16872100.0CHINET 2011金葡菌是临床最常见的革兰阳性菌第五页，本课件共有61页MRSAMRSA可引起各类感染可引起各类感染 骨髓炎食物中毒皮肤烫伤综合征T中毒休克综合征脓疱病疖肺炎眼内炎心内膜炎蜂窝织炎第六页，本课件共有61页Annual Death Rates in the United StatesAnnual Death Rates in the United StatesSelected Infectious DiseasesSelected Infectious DiseasesNo.of patients diedBoucher HW and Corey GR.Clin Infect Dis 2008;46:S344-9.MRSA感染的死亡病例数高于AIDS的死亡病例数第七页，本课件共有61页8S.aureus is the most common pathogen of HAP(n=656)Percentage(%)S aureusMRSAP aeruginosaE coliK pneumoniaeEnterococcus sppE.faecalisCandida sppC.albicansCoNSAcinetobacter sppA.baumanniiEnterobacter sppE.cloacaeS.marcescensS.maltophiliaC.freundiiOthersKim JM.Am J Infect Control 2000;28:454-8.91%of S.aureus were MRSA第八页，本课件共有61页9MRSA is the third most common pathogen of HAP in ChinaA multi-center survey conducted in 12 hospitals in China from 2008 to 2010 to know the incidence and causative pathogens of HAP.Liu YN,unpublished data by personal communicationPercentage(%)A.baumannii P.aeruginosaS.aureusK.pneumoniaeC.albicansS.maltophiliaE.coliE.cloacaeC.Tropical CoNS The incidence of HAP varies from 0.9-4.1%in different hospitals in ChinaA.fumigatus第九页，本课件共有61页Doern GV et al:Diagn Microbiol Infect Dis 1999;34:65Brook I:Int J Surg 2008;6:328Chira S,Miller LG:Epidemiol Infect 2010;138:313oGram-positive organisms predominate(60-70%)nS.aureus-48%in one studynGroup A -hemolytic streptococci-26%oGram-negative organisms involved in 25-35%of infectionsoAnaerobic and fungal organisms are uncommonoPolymicrobial infections are encountered:nEspecially with deeper soft tissue infectionsMicrobiology in Skin/Soft Tissue Infections金葡菌是皮肤软组织感染的最常见病原菌金葡菌是皮肤软组织感染的最常见病原菌第十页，本课件共有61页11OUTLINEoMRSA的临床重要性的临床重要性oMRSA的药物敏感性及变迁的药物敏感性及变迁oMRSA感染的抗菌治疗感染的抗菌治疗第十一页，本课件共有61页Prevalence of MRSA and MRCNS in Shanghai region since 1999第十二页，本课件共有61页问题问题2、MRSA对万古霉素的耐药性如何？对万古霉素的耐药性如何？是否存在是否存在MIC漂移（漂移（MIC creep）？）？第十三页，本课件共有61页MSSA(2954株)与MRSA(3033株)的耐药率（%）CHINET 2011耐药监测数据显示，MRSA对万古霉素、利奈唑胺100敏感第十四页，本课件共有61页15Twelve VRSA(Vancomycin resistant S.aureus)reported in the USoTwelve cases from USAoPositive for the vanA geneoMedian vancomycin MIC:512 mg/LoAll patients had prior MRSA colonization or infectionsoAll had severe underlying factorsAAC 2009;53:4580-7第十五页，本课件共有61页16Five VRSA reported in AsiaoIndia:3 strains n2 strains:vancomyicn MIC 32 or 64 mg/L,vanA negative in addition,found 6 VISA strains (Tiwari HK,BMC Infect Dis 2006;6:156)nOne VRSA vancomycin MIC64 mg/L,vanA positive (Saha B,et al.J Med Microbiol 2008;57,7279)oIran:2 strainsnOne isolate had a vancomycin MIC of 64 mg/LnOther one had a vancomycin MIC of 512 mg/L and vanA positive (Aligholi M,et al.Med Princ Pract 2008;17(5):432)第十六页，本课件共有61页17异质性万古霉素中介金葡菌（异质性万古霉素中介金葡菌（hVISA）在中国的发生情况在中国的发生情况o1012株株MRSA于于2002-7年（主要为年（主要为05-07）分离自）分离自14个城市个城市o检测方法：含药平皿及检测方法：含药平皿及MET初筛，菌群分析策略初筛，菌群分析策略-曲线下面积方法确曲线下面积方法确认认nhVISA 血培养血培养20013.1(26/199)VISA 1(万古万古 MIC 4mg/L)非血培养非血培养81215.7（128/812）o2007年分离自年分离自14个城市个城市315株株MRSA，hVISA 9.5(30/315)(陈宏斌，中华检验医学杂志陈宏斌，中华检验医学杂志 2009;32(11):1223-7)Sun W,AAC 2009;53(9):3642-9第十七页，本课件共有61页 How to detect VISA and hVISA?第十八页，本课件共有61页19Clinical Infectious Diseases 2007;44:153642oVISA was identified as S“by disc diffusion17mm zone“S”MIC 8ug/ml“I”Disc diffusion and E-TestE-Test:MIC 2,but disc diffusion:for“S”E-Test:MIC=2,but disc diffusion:for“S”E-Test:MIC2,but disc diffusion:for“S”MIC 8ug/ml“I”17mm zone“S”MIC 8ug/ml“I”17mm zone“S”MIC 8ug/ml“I”17mm zone“S”MIC 8ug/ml“I”17mm zone“S”MIC 8ug/ml“I”VISA strains(vanco MIC 4-8)hVISA(vanco MIC 1-2)CAN NOT be detected by disk diffusion method第十九页，本课件共有61页20MIC testing is recommended by CLSI to determine vancomycin susceptibility for MRSA since 2009*BHI+6g/ml vancomycin*BHI+6g/ml vancomycin*send to reference labsend to reference lab第二十页，本课件共有61页21Comparison of laboratory detection methods of hVISAMethodSensitivitySpecificityVancomycin broth MIC11%100%BHIA+BHIA6V48 h,4.512%48 h,68100%MHA+MHA5T48 h,6579%48 h,3595%MHA+MHA5T48 h,98%48 h,53%BHIA+Vancomycin 5g/ml，10l of a 0.5 McFarlandstandard suspension48 h,120%48 h,5999%Simplified PAP*48 h,71%48 h,88%Macromethod Etest(MET)48 h,6998.5%48 h,8994%Etest GRD24 h,7077%48 h,9394%24 h,98100%48 h,8295%Benjamin P.CLINICAL MICROBIOLOGY REVIEWS.2010;23:99-139.hVISA can not be detected by routine methodsPopulation analysis profile(PAP)is“gold standard”,but it is labor-intensive and impractical for clinical lab.Testing for hVISA is not routinely recommended 第二十一页，本课件共有61页Vancomycin MIC creep：地区差异：地区差异22Journal of Antimicrobial Chemotherapy(2007)60,788794第二十二页，本课件共有61页23全球九国全球九国10年（年（2001-2010）分离）分离MRSA万古霉素万古霉素MIC几何均数在几何均数在1mg/L左右左右(0.661.13)Reynolds R,ECCMID 2012,P1215 第二十三页，本课件共有61页Vancomycin Susceptibility in MRSA Over 10 Years:MIC Decrease After a Transient CreepVancomycin MIC mg/L:n(%)Year(n)0.5-0.751.001.502.003.0-4.0Means SDVanco.use for MRSA02-03(186)06(3.2)86(46.2)85(45.7)9(4.8)1.78 0.3995.0%05-06(184)1(0.5)2(1.1)95(51.6)70(38.0)16(8.7)1.82 0.4791.0%08-09(172)00110(64.0)61(35.5)1(0.6)1.69 0.2693.2%10-12(135)2(1.5)15(10.9)97(70.8)20(14.6)1(0.78)1.52 0.3093.5%ICAAC 2012.C2-1391 R.Khatib,Grosse Pointe Woods,MI 677 isolates tested.Van MIC was stable between 2002-3 and 2005-6,increased in 2008-9 and decreased in 2010-2The reason for this decrease is uncertain.It may be due to reduced use of V or higher drug concentrations.The targeted V trough levels were increased in early 2010 to 15-20 g/L 第二十四页，本课件共有61页25OUTLINEoMRSA引起的常见感染引起的常见感染oMRSA的药物敏感性及变迁的药物敏感性及变迁oMRSA感染的抗菌治疗感染的抗菌治疗第二十五页，本课件共有61页问题问题3、目前临床应用的治疗、目前临床应用的治疗MRSA感染的抗菌感染的抗菌药主要有哪些？各有什么优缺点？药主要有哪些？各有什么优缺点？第二十六页，本课件共有61页抗抗MRSA的最主要抗菌药物的最主要抗菌药物27万古霉素万古霉素Vancomycin利奈唑胺利奈唑胺Linezolid达托霉素达托霉素Daptomycin类型类型糖肽类糖肽类噁噁唑烷酮类唑烷酮类环脂肽类环脂肽类抗菌类型抗菌类型杀菌剂杀菌剂（葡萄球菌）（葡萄球菌）抑菌剂抑菌剂（肠球菌（肠球菌/葡萄球菌）葡萄球菌）快速杀菌剂快速杀菌剂（革兰阳性菌）（革兰阳性菌）抗菌谱抗菌谱G(+)G(+)G(+)作用部位作用部位细胞壁细胞壁核糖体核糖体 RNA 亚基亚基细胞膜细胞膜第二十七页，本课件共有61页万古霉素的优点与缺点优 点o临床使用近临床使用近50年，革兰年，革兰阳性菌对其仍高度敏感阳性菌对其仍高度敏感o治疗革兰阳性菌感染最治疗革兰阳性菌感染最为经典的药物为经典的药物o临床适应证最广临床适应证最广缺 点oMRSA敏感性下降问题敏感性下降问题o组织浓度组织浓度o不良反应不良反应第二十八页，本课件共有61页万古霉素万古霉素万古霉素万古霉素利奈唑胺利奈唑胺利奈唑胺利奈唑胺达托霉素达托霉素达托霉素达托霉素复杂性皮肤软组织感染复杂性皮肤软组织感染复杂性皮肤软组织感染复杂性皮肤软组织感染 血流感染与自身瓣膜心内膜炎血流感染与自身瓣膜心内膜炎血流感染与自身瓣膜心内膜炎血流感染与自身瓣膜心内膜炎 人工瓣膜心内膜炎人工瓣膜心内膜炎人工瓣膜心内膜炎人工瓣膜心内膜炎(联合庆大、利福平联合庆大、利福平联合庆大、利福平联合庆大、利福平)肺炎肺炎肺炎肺炎 骨髓炎骨髓炎骨髓炎骨髓炎 (超适应证）超适应证）超适应证）超适应证）(超适应证）超适应证）超适应证）超适应证）植入物相关骨髓炎、关节炎植入物相关骨髓炎、关节炎植入物相关骨髓炎、关节炎植入物相关骨髓炎、关节炎 (超适应证）超适应证）超适应证）超适应证）(超适应证）超适应证）超适应证）超适应证）脑膜炎，脑脓肿等脑膜炎，脑脓肿等脑膜炎，脑脓肿等脑膜炎，脑脓肿等CNSCNS感染感染感染感染 (超适应证）超适应证）超适应证）超适应证）不同MRSA感染的抗菌药物选择Liu C,Clin Infect Dis 2011;52(3):2852011 IDSA MRSA指南指南万古霉素的临床适应证最广第二十九页，本课件共有61页万古霉素治疗药物监测万古霉素治疗药物监测（TDM）相关问题）相关问题oo监测血清监测血清监测血清监测血清谷浓度谷浓度谷浓度谷浓度监测给药剂量最准确、实用；监测给药剂量最准确、实用；监测给药剂量最准确、实用；监测给药剂量最准确、实用；oo应在达到稳态后采集标本（第应在达到稳态后采集标本（第应在达到稳态后采集标本（第应在达到稳态后采集标本（第4-54-5次给药前）次给药前）次给药前）次给药前）；oo并非所有患者需要血药浓度监测；并非所有患者需要血药浓度监测；并非所有患者需要血药浓度监测；并非所有患者需要血药浓度监测；oo监测谷浓度对象：监测谷浓度对象：监测谷浓度对象：监测谷浓度对象：pp肾功能损害；肾功能损害；肾功能损害；肾功能损害；pp肥胖；肥胖；肥胖；肥胖；pp表观分布容积波动；表观分布容积波动；表观分布容积波动；表观分布容积波动；第三十页，本课件共有61页31oTrough serum vancomycin concentrations always be maintained at 10 mg/L to avoid the development of resistance(BIII)oTo improve clinical outcomes of hospital-acquired pneumonia caused by S.aureus,trough serum vancomycin concentrations of 1520 mg/L are recommended(Note:much higher than former concentration of 5-10 mg/L)(BIII)oTo achieve rapid attainment of this target concentration for seriously ill patients,a loading dose of 2530 mg/kg)(1.5-1.8 g)(based on actual body weight)can be considered.(BIIIoTrough serum vancomycin concentrations in that range should achieve an AUC/MIC of 400 for most patients if the MIC is 580,肠球菌感染肠球菌感染 638，预测，预测95患者可达临床有效患者可达临床有效第三十二页，本课件共有61页糖肽类的耳肾毒性问题o在上市之初，因纯度的问题，毒性较明显在上市之初，因纯度的问题，毒性较明显o纯度提高后，耳肾毒性发生率低纯度提高后，耳肾毒性发生率低o长疗程用药需注意药物热的出现可能长疗程用药需注意药物热的出现可能第三十三页，本课件共有61页利奈唑胺的优点与缺点优 点o新类别抗菌药新类别抗菌药o对对VRE、VISA、hVISA等具抗菌活性等具抗菌活性o临床适应证较广临床适应证较广o同时有静脉及口服制剂同时有静脉及口服制剂缺 点o抑菌剂抑菌剂o静脉导管相关血流感染静脉导管相关血流感染疗效问题疗效问题o耐药性出现较快耐药性出现较快o骨髓抑制骨髓抑制第三十四页，本课件共有61页万古霉素万古霉素万古霉素万古霉素利奈唑胺利奈唑胺利奈唑胺利奈唑胺达托霉素达托霉素达托霉素达托霉素复杂性皮肤软组织感染复杂性皮肤软组织感染复杂性皮肤软组织感染复杂性皮肤软组织感染 血流感染与自身瓣膜心内膜炎血流感染与自身瓣膜心内膜炎血流感染与自身瓣膜心内膜炎血流感染与自身瓣膜心内膜炎 人工瓣膜心内膜炎人工瓣膜心内膜炎人工瓣膜心内膜炎人工瓣膜心内膜炎(联合庆大、利福平联合庆大、利福平联合庆大、利福平联合庆大、利福平)肺炎肺炎肺炎肺炎 骨髓炎骨髓炎骨髓炎骨髓炎 (超适应证）超适应证）超适应证）超适应证）(超适应证）超适应证）超适应证）超适应证）植入物相关骨髓炎、关节炎植入物相关骨髓炎、关节炎植入物相关骨髓炎、关节炎植入物相关骨髓炎、关节炎 (超适应证）超适应证）超适应证）超适应证）(超适应证）超适应证）超适应证）超适应证）脑膜炎，脑脓肿等脑膜炎，脑脓肿等脑膜炎，脑脓肿等脑膜炎，脑脓肿等CNSCNS感染感染感染感染 (超适应证）超适应证）超适应证）超适应证）不同MRSA感染的抗菌药物选择Liu C,Clin Infect Dis 2011;52(3):2852011 IDSA MRSA指南指南利奈唑胺的临床适应证较广第三十五页，本课件共有61页新类别抗菌药研发困难o近年开发新类别抗菌药少近年开发新类别抗菌药少n利奈唑胺利奈唑胺(linezolid)：恶唑烷酮类：恶唑烷酮类(oxazolidinones)n达托霉素达托霉素(daptomycin):脂肽类脂肽类o现有类别药物的改进现有类别药物的改进n替利霉素替利霉素(telithromycin)：酮内酯类：酮内酯类ketolides,为大环内酯类红霉素为大环内酯类红霉素A的衍生物的衍生物n替加环素替加环素(tigecycline)：甘氨酰环素类：甘氨酰环素类glycylcyclines为四环素类米为四环素类米诺环素的衍生物诺环素的衍生物n特拉万星特拉万星(telavancin)：脂糖肽类：脂糖肽类lipoglycopeptides，为万古霉素，为万古霉素的衍生物的衍生物第三十六页，本课件共有61页利奈唑胺对革兰阳性菌具良好抗菌作用致病菌致病菌菌株数菌株数MIC90(g/ml)MIC范围范围(g/ml)敏感率敏感率(%)金黄色葡萄球菌金黄色葡萄球菌324020.5-4100 MRSA109220.5-4100 MSSA214820.5-4100凝固酶阴性葡萄凝固酶阴性葡萄球菌球菌74820.5-499.6肠球菌肠球菌86420.25-899.3 VRE8620.5-897.7肺炎链球菌肺炎链球菌65510.12-2100草绿色链球菌草绿色链球菌21610.06-2100-溶血性链球菌溶血性链球菌39810.25-2100Jones RN et al.Diagnostic Microbiology and Infectious Disease.2009;65:404413.2008年对24个国家64个医学中心收集的6121株G+球菌进行的耐药监测结果第三十七页，本课件共有61页利奈唑胺不推荐用于导管相关血流感染利奈唑胺不推荐用于导管相关血流感染20072007年年FDAFDA向医生发出警告向医生发出警告o治疗导管相关感染的研究表明治疗导管相关感染的研究表明2 2 利奈唑胺利奈唑胺治疗首次用药后治疗首次用药后8484天内的天内的死亡率死亡率21.5%21.5%(78/363)(78/363)，而对照，而对照组为组为16.6%(58/363)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.第三十八页，本课件共有61页 美国美国 Leader program 2004-2010Leader program 2004-2010耐利奈唑胺的金葡菌发生率耐利奈唑胺的金葡菌发生率Diagnostic Microbiology and Infectious Disease 74(2012)5461耐药率(%)N=21642全球监测显示，MRSA对利奈唑胺的耐药率低第三十九页，本课件共有61页Clinical outbreak of linezolid-resistant Staphylococcus aureusin an intensive care unit in Spain(Hospital Clinico San Carlos)Snchez Garca M,JAMA.2010;303(22):2260-4第四十页，本课件共有61页 Mechanism of linezolid resistanceoMutations in domain V of 23S rRNAoMutations in rplC(ribosomal protein L3)and rplD(L4)oMediated by Cfr methyltransferaseoUnknown mechanism第四十一页，本课件共有61页问题问题4、治疗、治疗MRSA肺炎，利奈唑肺炎，利奈唑胺是否优于万古霉素？胺是否优于万古霉素？第四十二页，本课件共有61页57.657.654.854.883.383.380.180.146.644.969.967.8020406080100PP at EOSMITT at EOSPP at EOTMITT at EOTProportion of patients with successful response(%)LinezolidLinezolidVancomycinVancomycin P=0.04295%CI 0.5-21.6P=0.04995%CI 0.1-19.8P=0.002 P=0.004n=165*n=7n=180*n=3n=186*n=2n=186*n=38n=201*n=23n=214*n=10n=205*n=19n=174*n=2Primary endpointSecondary endpoint*Number of excluded patientsZephyr study:linezolid is superior than vancomycin in the treatment of MRSA pneumoniaWunderink RG,CID 2012;54:621-9第四十三页，本课件共有61页60 Days Kaplan-Meier Survival rates were similar between two groups 60 Days Kaplan-Meier Survival rates were similar between two groups for mITT Populationfor mITT PopulationSurvival Distribution FunctionSurvival Distribution Function0.20.40.60.8010204060Time(Days)Time(Days)LinezolidLinezolid CensorVancomycinVancomycin Censor*10305094 subject deaths(15.7%)in linezolid arm100 subject deaths(17.0%)in vancomycin arm Controversy:is linezolid really better than vancomycin?第四十四页，本课件共有61页57.657.654.854.883.383.380.180.146.644.969.967.8020406080100PP at EOSMITT at EOSPP at EOTMITT at EOTProportion of patients with successful response(%)LinezolidLinezolidVancomycinVancomycin P=0.04295%CI 0.5-21.6P=0.04995%CI 0.1-19.8P=0.002 P=0.004n=165*n=7n=180*n=3n=186*n=2n=186*n=38n=201*n=23n=214*n=10n=205*n=19n=174*n=2Primary endpointSecondary endpoint*Unknown excluded pts from analysis A large number of mITT patients excluded from the statistic populationControversy:is linezolid really better than vancomycin?第四十五页，本课件共有61页 Higher proportion of cases with MRSA bacteremia and mechanical ventilation in the vancomycin armCharacteristicBaseline Clinical CharacteristicsVancomycin armNo.(%)Linezolid armNo.(%)Mechanical ventilation 130(73.9)115(66.9)Bacteremia20(10.8)9(5.2)The baseline clinical characteristics of vancomycin arm are seems to be more complicated and severeControversy:is linezolid really better than vancomycin?第四十六页，本课件共有61页47针对MRSA医院肺炎的荟萃分析提示 万古霉素的临床疗效与利奈唑胺相仿Walkey AJ,CHEST 2010;DOL 1378/1556.RR(95%CI)1.09(0.82-1.44)1.23(0.72-2.07)0.97(0.78-1.19)1.02(0.89-1.16)0.93(0.63-1.36)0.93(0.39-2.24)1.17(0.73-1.87)1.41(0.64-3.08)1.02(0.93-1.12)临床成功例数/总数322/84171/20320/50114/32151/5723/4711/5119/3813/74利奈唑胺糖肽类62/19326/49111/30252/5930/576/2618/429/72304/800研究/亚组研究Rubenstein 2001Stevens 2002Wunderink 2003Wilcox 2004Cepeda 2004Kohno 2007Lin 2007Wunderink 2008异质性 X2=2.20，p=0.95，I2=0%总体疗效，p=0.6350.20.512利于糖肽类利于利奈唑胺荟萃分析第四十七页，本课件共有61页达托霉素的优点与缺点优 点o新类别抗菌药新类别抗菌药o快速杀菌作用快速杀菌作用o对对VRE、VISA、hVISA等具抗菌活性等具抗菌活性缺 点o无肺炎适应证无肺炎适应证o价格较高价格较高oCPK升高升高o在中国的问题：血培养在中国的问题：血培养阳性率低阳性率低第四十八页，本课件共有61页Bacterial Growth Phases:Bacterial Growth Phases:达托霉素对静止期细菌也具杀菌作用达托霉素对静止期细菌也具杀菌作用oStationary-phase bacteria:nare non-dividing and metabolically arrested.nAssociated with persistent infections(endocarditis and osteomyelitis)nAssociated with biofilm-related infections(catheters,grafts,and foreign bodies)oThe mechanism of action of many bactericidal antibiotics requires ongoing cell division(log phase)oNormally bactericidal antibiotics(e.g.,beta-lactams)may display limited activity against stationary phase cellsMascio et al.,AAC 2007 p.42554260 Vol.51,No.12.第四十九页，本课件共有61页TissueVancomycinLinezolidDaptomycinBone7%-13%60%117%CSF0%-18%70%5-6%Lung alveolar11%-17%100%-450%10%Blister fluid20%-30%104%70%Muscle30%94%Peritoneal fluid20%61%40%Blood clot tissue70%Drug Penetration:%Tissue/Serum达托霉素在多数组织的浓度较高第五十页，本课件共有61页万古霉素万古霉素万古霉素万古霉素利奈唑胺利奈唑胺利奈唑胺利奈唑胺达托霉素达托霉素达托霉素达托霉素复杂性皮肤软组织感染复杂性皮肤软组织感染复杂性皮肤软组织感染复杂性皮肤软组织感染 血流感染与自身瓣膜心内膜