替加环素治疗多重耐药菌感染(课堂PPT).ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,替加环素,-,海正力星能有效治疗多重耐药菌感染吗？,1,内 容,流行病学资料,替加环素的特点及疗效,海正力星与原研的比较,小结,2,流行病学资料,3,MDR,、,XDR,、,PDR,细菌已成为全球关注的焦点,在全球范围内，,“ESKAPE”,耐药已成为导致治疗困难及死亡的重要原因,1,“,ESKAPE,”,耐药现象日益严重，但当前新型抗菌药物的研发逐渐减缓，未来可能面临无药可用的局面,3,新药数量,1983-1987,1988-1992,1993-1997,1998-2002,2003-2007,1.Rice LB et al.The Journal of Infectious Diseases 2008;197:107981,2.www.who.int/world-health-day/zh/,3.Boucher HW et al.Clinical Infectious Diseases 2009;48:112,4,抗生素应用带来的耐药问题,未来抗微生物感染治疗的关键在于控制致病原的进化,而不是只针对病原体的治疗药物本身！,Hoban DJ.Clinical cornerstone 2003,19th Century:,No,antibiotics,21st Century:,The end,of antibiotics?,20th Century:,Antibiotics as,“miracle,drugs”,5,6,细菌,株数,大肠埃希菌,11860,28,克雷伯菌属,6981,16.5,不动杆菌属,6723,15.8,假单胞菌属,6334,15,肠杆菌属,2519,5.9,嗜麦芽窄食单胞菌,1889,4.4,2011 CHINET,耐药监测前,6,位革兰阴性菌菌种分布,7,2011,年,CHINET 15,家医院,6981,株克雷伯菌属耐药率（,%,）,对亚胺培南和美罗培南的耐药率上升,8,浙江省人民医院2012年,1072株肺炎克雷伯菌对常用药物的药敏试验检测结果,抗生素,折点,株数,%R,%I,%S,替加环素,S=8,193,4.8,7.5,87.7,阿米卡星,S=64,1071,13.6,0.2,86.2,妥布霉素,S=16,1069,19.6,15.2,65.1,美洛培南,20-22,448,21.4,1.6,77,头孢吡肟,S=32,1071,23.7,2.3,73.9,超广谱,-内酰胺酶(+),1058,25.1,复方新诺明,S=4,1069,25.6,0,74.4,庆大霉素,S=16,1071,25.6,1.1,73.3,亚胺培南,S=4,1071,25.7,1.3,73,哌拉西林,/,他唑巴坦,S=128,1071,26.5,1.5,72,厄他培南,S=1,1065,26.9,1.6,71.5,头孢替坦,S=64,882,27.2,1.8,71,9,2011,年,CHINET 15,家医院,6012,株铜绿假单胞菌耐药率（,%,）,10,2011,年,CHINET 15,家医院,6723,株不动杆菌属,(,鲍曼不动,88.6%),细菌的耐药率（,%,）,对多黏菌素的耐药率低,对亚胺培南、美罗培南的耐药率,60%,（,）,对两种舒巴坦合剂的耐药率,（,40%-60%,）,对多数抗菌药的耐药率,60%,11,2011,年,CHINET,各医院泛耐药株数,医院,铜绿假单胞菌,鲍曼不动杆菌,PDR,株数总株数,（）,PDR,株数,总株数,（）,华山医院,18/642,2.8,232/560,41.4,瑞金医院,11/433,2.5,118/421,28.0,协和医院,3/686,0.4,295/700,42.1,同济医院,7/613,1.1,85/374,22.7,浙医一附院,5/630,0.8,128/659,19.4,广州一附院,0/486,0.0,0/438,0.0,重医一附院,3/258,1.2,115/362,31.8,北京医院,20/431,4.6,26/117,22.2,儿科医院,0/159,0.0,121/340,35.6,儿童医院,0/118,0.0,45/184,24.5,甘肃人民医院,0/115,0.0,7/182,3.8,新疆医大一附院,1/408,0.2,0/376,0.0,安徽医大一附院,17/454,3.7,76/448,17.0,昆明医大一附院,24/255,9.4,13/365,3.6,浙江邵逸夫医院,0/324,0.0,1/432,0.2,合计,109/6012,1.8,1262/5958,21.2,2010,86/5080,1.7,1058/4949,21.4,12,替加环素的特点及疗效,13,替加环素,:,甘氨酰环类的新型抗菌药物,在,9,位上增加甘氨酰胺基,增强了体外抗菌活性和抗菌谱,(G,+,/G,-,/,非典型病原体,/,厌氧菌,/,耐药的,G-/,耐药,G+,）,避免了四环素类的耐药机制（核糖体保护、外排泵机制）,通过与核糖体,30S,亚单位结合、阻止氨酰化,tRNA,分子进入核糖体,A,位而抑制细菌蛋白质合成,1,、产品说明书。,2,、,Zhanel et al.Expert Rev.Anti Infect.Ther.2006;4(1):9-25.,14,替加环素的,作用机制,替加环素通过与核糖体,30S,亚单位结合、阻止氨酰化,tRNA,分子进入核糖体,A,位而抑制细菌蛋白质合成,替加环素,15,替加环素药代动力学特性,分布,海正力星的稳定状态分布容积约为,500-700,升,(7,至,9 L/kg),，,且其分布范围要超过血浆的分布容积，可广泛分布到全身各个组织,根据临床研究观察,(0.1,至,1.0 g/mL),，替加环素的体外血浆蛋白结合率约为,71%,至,89%,1.,海正力星,(,注射用替加环素,),产品说明书,3.Peterson LR et al.Int J Antimicrob Agents.2008;32 Suppl 4:S215,-222.,组织,/,组织液,穿透率,组织,vs.,血清,AUC,24,比值,部位,/,组织,AUC,0-12,比值,组织,/,血清,胆囊,a,38,倍,23/14,结肠,a,2.3,倍,2.6/1.8,皮肤水疱液,b,比血浆低,26%,1.6/2.18,肺泡细胞,b,78,倍,134/1.73,上皮细胞衬液,b,比血浆高,32%,2.28/1.73,肺组织,a,8.6,倍,2.0/2.0,滑液,b,0.58,倍,0.3/0.3,骨,a,0.35,倍,0.4/0.3,患者手术前接受单剂,100mg,静脉滴注；多剂替加环素用药数据并未评估,健康人体接受首剂,100mg,静脉滴注，随后每,12,小时接受,50mg,替加环素静脉滴注,16,替加环素：药代动力学特性,抗生素后效应,(PAE),替加环素为时间依赖性抗菌药物，并具有中至长时间的,PAE,，因此，其,PK/PD,的评价参数为,AUC/MIC,4.Dilip Nathwani,et al.,Int J of Antimicrobial Agents 25(2005)185192,对肺炎链球菌,PAE,为,8.9h,1,、体外试验显示，替加环素对各种金葡菌的,PAE,可持续,3.4-4h,，对大肠埃希菌,(,包括带有特定抗药性决定因子的菌株,),可持续,1.8-2.9h,2,、,一,项,嗜中性白血球缺乏症小鼠大腿局部感染模型研究,显示，,替加环素体内的,PAE,持续时间极长，对肺炎链球菌为,8.9h,1,1,2,17,替加环素：药代动力学特性,代谢和排泄,代谢,替加环素在体内并不经过广泛的代谢,在接受,14,C-,替加环素的男性健康志愿者中，替加环素是尿液和粪便中发现的主要,14,C,标记物质，但也可见葡萄糖醛酸苷、,N-,乙酰代谢产物和替加环素异构体，每种成分不超过给药剂量的,10%,排泄,双通道排泄途径，约,有,59%,通过胆汁,/,粪便排泄消除,，,33%,经尿液排泄,总剂量的,22%,以替加环素原型经尿液排泄,代谢产物没有任何活性,1.,海正力星,(,注射用替加环素,),产品说明书,.,胆汁,/,粪便,尿,其它,尿,其它,18,替加环素的抗菌谱,6.Gilbert DN,et al.,热病,.40,版,2011.,9.,杨青等,.,中华检验医学杂志,.2003;26(6):342-345.,10.Hu F.et al.J Med Microbiol.2011.,G,+,菌,G,-,菌,非典型病原体,厌氧菌,MRSA,VRE,其他,G,+,菌,产,ESBL,细菌,CR-AB,CRE,铜绿假单胞菌,*,其他,G,-,菌,替加环素,糖肽类,碳青霉烯类,x,x,x,x,x,x,x,x,x,x,x,x,x,MRSA:,耐甲氧西林金黄色葡萄球菌；,VRE:,耐万古霉素肠球菌；,ESBL:,超广谱,内酰胺酶；,CR-AB:,耐碳青霉烯鲍曼不动杆菌；,CRE:,耐碳青霉烯肠杆菌,#,：不包含真菌；：具有抗菌活性，临床敏感率,60%,；,X,：代表临床无效、无数据或敏感率,30%,；*：替加环素对,G-,菌中铜绿假单胞菌天然耐药；,：部分基因型的,VRE,对替考拉宁敏感,11.Stephen P.Hawser,et al.International Journal of Antimicrobial Agents.2010;36:288294.,12.Michael J.Dowzickya,et al.International Journal of Antimicrobial Agents.2011;37:562-566.,13.Ting-ting Qu et al.Journal of Clinical Microbiology.2009;47(12):4194-4196.,19,替加环素对,G,-,菌的抗菌活性,抗菌药物,大肠埃希菌,(n=548),克雷伯菌,(n=317),肠杆菌属,(n=108),柠檬酸杆菌属,(n=30),MIC,90,%S,MIC,90,%S,MIC,90,%S,MIC,90,%S,替加环素,0.5,100,2,95.3,2,93.5,0.5,100,亚胺培南,0.25,100,0.5,98.1,1,94.4,1,100,美罗培南,0.032,100,0.064,99.1,0.125,98.1,0.064,100,抗菌药物,沙雷菌属,(n=28),鲍曼不动杆菌,(n=343),嗜麦芽窄食单胞菌,(n=51),MIC,90,%S,MIC,90,%S,MIC,90,%S,替加环素,2,100,2,90.1,2,亚胺培南,1,92.9,64,36.4,256,美罗培南,0.125,100,64,36.7,256,14.,杨启文等,.,中华检验医学杂志,.2011;34(5):422-430.,20,替加环素对,G,+,菌的抗菌活性,抗菌药物,MRSA(n=147),MSSA(n=97),MRSCoN(n=144),MSSCoN(n=27),MIC,90,%S,MIC,90,%S,MIC,90,%S,MIC,90,%S,替加环素,0.5,100,0.25,100,0.5,100,0.25,100,万古霉素,1,100,1,100,1,100,1,100,抗菌药物,粪肠球菌,(n=80),屎肠球菌,(n=125),MIC,90,%S,MIC,90,%S,替加环素,0.125,100,0.064,100,万古霉素,2,100,1,99.2,MRSA:,甲氧西林耐药金黄色葡萄球菌；,MSSA:,甲氧西林敏感金黄色葡萄球菌；,MRSCoN,:,甲氧西林耐药凝固酶阴性葡萄球菌；,MSSCoN:,甲氧西林敏感凝固酶阴性葡萄球菌,14.,杨启文等,.,中华检验医学杂志,.2011;34(5):422-430.,21,临床治愈率,(%),ME,人群,CE,人群,m-,mITT,人群,替加环素与亚胺培南,/,西司他丁的临床治愈率相当,594/685,607/697,441/512,442/513,506/631,514/631,替加环素治疗,cIAI,95%CI,：,-0.4%,(-4.1%to3.3%),15.Babinchak T et al.Clinical Infectious Diseases 2005;41:S35467.,95%CI,：,0.0%,(-4.5%to 4.4%),95%CI,：,-1.3%,(-5.8%to 3.2%),P 0.0001,非劣效比较,22,替加环素,治疗不同疾病类型的,cIAI,复杂性,阑尾炎,复杂性,胆囊炎,腹腔,脓肿,肠穿孔,复杂性,憩室炎,胃,/,十二指肠穿孔,腹膜炎,其他,234,263 262,70,69 74,40 35,51 45,38 29,51 40,23 30,32 42,23 23,25 25,16 18,18 20,2 3,3 5,n=,治愈率,(%),N=,替加环素治疗不同疾病类型的腹腔感染具有较好的临床治愈率,95%CI,：,1.1%(6.8%to 4.6%),95%CI,：,2.5%(6.4%to 11.4%),95%CI,：,0.7%(17.0%to 18.8%),95%CI,：,2.0%(17.0%to 21.8%),95%CI,：,0.4%(22.1%to 21.7%),95%CI,：,0.0%(20.6%to 20.6%),95%CI,：,1.1%(27.4%to 23.8%),95%CI,：,6.7%(56.6%to 60.0%),15.Babinchak T et al.Clinical Infectious Diseases 2005;41:S35467.,23,替加环素治疗,cIAI,的细菌清除率,微生物结果,(%),替加环素与亚胺培南,-,西司他丁的细菌学清除率相当,441/512,442/513,60/512,11/512,3/513,68/513,清除,持续感染,二重感染,95%CI:0.0%,(-4.5%to 4.4%),P 0.0001,非劣效比较,15.Babinchak T et al.Clinical Infectious Diseases 2005;41:S35467.,24,替加环素治疗重症,cIAI,临床疗效,治疗成功率,(%),成功率包括治愈和改善，治愈指感染症状完全缓解，改善指感染症状有所改善但未达到完全缓解,替加环素有效治疗重症腹腔内感染，治疗成功率达,75%,201/267,n=71,n=129,164/215,16.Eckmann C et al.Chemotherapy.2011;57:275284,25,替加环素治疗,CAP,临床治愈率与左氧氟沙星相当,替加环素治疗,CAP,的临床治愈率均在,80%,以上,临床治愈率,(%),253/282,321/403,319/394,252/292,P0.001,Tanaseanu C et al.Diagnostic Microbiology and Infectious Disease.2008;61:329-338.,ME,人群,m-mITT,人群,ME,：,微生物可评估；,m-mITT,：,微生物修正意向治疗,26,替加环素治疗伴随其它基础疾病,CAP,患者疗效,替加环素治疗伴随充血性心力衰竭、糖尿病、,COPD,等其它基础疾病的,CAP,患者同样有效,临床治愈率,(%),22/22,14/21,34/35,28/37,26/32,23/30,Tanaseanu C et al.Diagnostic Microbiology and Infectious Disease.2008;61:329-338.,27,227/263,226/259,101/116,106/116,24/30,19/23,9/9,4/4,替加环素,万古霉素,-,氨曲南,替加环素,治疗,cSSSI,疗效,9/9,4/4,临床治愈率,(%),227/263,226/259,101/116,106/116,24/30,19/23,9/9,4/4,软组织感染,脓肿,感染性溃疡,烧烫伤,其他,9/9,4/4,Ellis-Grosse EJ et al.Clin Infect Dis.2005;41(Suppl 5):S341-353.,95%CI,：,-0.9%,(-7.1%to 5.2%),95%CI,：,-4.3%,(-13.2%to 4.5%),95%CI,：,-2.6%,(-25.0%to 22.4%),95%CI,：,0.0%,(-37.1%to 37.1%),95%CI,：,0.0%,(-60.4%to 60.4%),不同疾病类型的,cSSSI,的临床治愈率,28,替加环素,万古霉素,-,氨曲南,替加环素治疗伴有合并症的,cSSSI,临床疗效,60/83,65/85,22/29,21/28,19/23,伴发糖尿病,伴发周边血管疾病,伴发基线菌血症,21/24,Ellis-Grosse EJ et al.Clin Infect Dis.2005;41(Suppl 5):S341-353.,临床治愈率,(%),95%CI,：,-4.2%,(-18.0%to 9.8%),95%CI,：,0.9%,(-23.1%to 25.0%),95%CI,：,-4.9%,(28.9%to 19.1%),29,细菌清除率,(,%,),25/32,25/33,25/27,8/8,4/5,24/29,大肠埃希菌,MRSA,脆弱拟杆菌,化脓性链球菌,30/32,MRSA:,耐甲氧西林金黄色葡萄球菌,粪肠球菌,(,非万古霉素耐药,),22/24,14/16,6/7,21,、,Ellis-Grosse EJ et al.Clin Infect Dis.2005;41(Suppl 5):S341-353.,无乳链球菌,7/8,11/13,咽峡炎链球菌,14/16,27/30,替加环素治疗,cSSSI,不同致病菌的细菌清除率,30,替加环素,不良反应发生率低,全身各系统不良事件,替加环素,(n=2514),对照组,a,(n=2307),全身,腹痛,6,4,脓肿,3,3,乏力,3,2,头痛,6,7,头痛,8,5,心血管系统,静脉炎,3,4,消化系统,腹泻,12,11,消化不良,2,2,恶心,26,13,呕吐,18,9,a.,万古霉素,/,氨曲南、亚胺培南,/,西司他丁、左氧氟沙星和利奈唑胺。,b.,替加环素治疗组患者的,LFT,异常情况更常见于治疗期后，而对照组患者更常见于治疗中,常见不良反应为轻至中度的恶心和呕吐,1.,海正力星,注射用替加环素,),产品说明书,全身各系统不良事件,替加环素,(n=2514),对照组,a,(n=2307),血液和淋巴系统,贫血,4,5,代谢与营养,4,3,碱性磷酸酶水平升高,3,2,淀粉酶升高,2,1,胆红素血症,3,1,BUN,水平升高,4,3,伤口愈合欠佳,5,3,低蛋白血症,4,5,SGOT,水平升高,b,5,5,SGPT,水平升高,b,神经系统,头晕,3,3,皮肤及其附属结构,皮疹,3,4,31,收集对碳青霉烯类抗生素敏感性下降肺炎克雷伯菌,25,株，,E test,法测定,10,种抗菌药物的,MIC,值,。,未发现对多粘菌素,E,和替加环素耐药的菌株,中国卫生检验杂志,2012,年第,22,卷第,6,期,P1420-1422,32,2000-2005,年在北美、拉丁美洲和欧洲的医学中心共收集,104,株产碳青霉烯酶,(,丝氨酸和金属,内酰胺酶,),的肠杆菌科细菌,采用微量稀释法测定替加环素和其他,25,种抗菌药物的抗菌活性。,33,产碳青霉烯酶的肠杆菌科细菌对多数抗菌药物耐药率高，替加环素的抑菌率达到,100%,。,34,2008,年,亚太,HAP,治疗共识,35,指南推荐,指南,指南推荐,IDSA,指南,推荐替加环素,单药治疗成人,cIAI,40,版,热病,推荐替加环素治疗以下感染性疾病,疾病：,轻中度住院治疗的憩室炎，直肠周围脓肿，腹膜炎，四肢、非糖尿病性蜂窝组炎的起始经验性治疗,高度耐药菌：,耐药肠球菌、金黄色葡萄球菌,南非,替加环素合理用药指南,推荐替加环素治疗成人,cSSSIs,和,cIAIs,2011,年欧洲专家对,IDSA,指南的评论和补充,推荐替加环素治疗如下疾病：,疾病,：,继发性腹膜炎、第三类型腹膜炎,耐药菌,：,MRSA,、,VRE,、产,ESBL,菌种、不动杆菌属、产碳青霉烯酶菌种（,CRE,）,36,海正力星与原研的比较,37,SFDA,正式批准海正力星,上市,2012,年,12,月,11,日海正力星正式获批：,获得首仿资质,SFDA,批准的适应症：,cSSSI,Complicated Skin And Skin Structure Infections,CAP,Community Acquired Pneumonia,cIAI,Complicated,Intra Abdominal Infections,1.,海正力星,(,注射用替加环素,),产品说明书,38,检测项目,标准规定,海正力星验证批样品状况,原研品,原研品,海正力星,101101,101102,101103,E49601,E54349,性状,橙色冻干块状物或粉末,应为橙色块状物或粉末,橙色块状物,橙色块状物,橙色块状物,橙色块状物,橙色块状物,鉴别（液相色谱）,供试品主峰的保留时间应与替加环素对照品峰一致,供试品主峰的保留时间应与替加环素对照品峰一致,符合规定,符合规定,符合规定,/,/,鉴别（吸收峰）,应在,246nm,的波长处有最大吸收,应在,246nm,的波长处有最大吸收,符合规定,符合规定,符合规定,/,/,酸度（,pH,值）,4.5-5.5,4.5-5.5,5.0,4.9,4.9,/,/,溶液的澄清度,溶液应澄清并呈黄至橙色,溶液应澄清并呈黄至橙色,澄清，黄色溶液,澄清，黄色溶液,澄清，黄色溶液,澄清，黄色溶液,澄清，黄色溶液,不溶性微粒,应符合规定,应符合规定,符合规定,符合规定,符合规定,/,/,降压物质,/,应符合规定,符合规定,符合规定,符合规定,/,/,可见异物,应符合规定,应符合规定,符合规定,符合规定,符合规定,/,/,无菌,应符合规定,应符合规定,符合规定,符合规定,符合规定,/,/,海正力星与,原研品（,泰阁,）,质量一致性比较,39,检测项目,标准规定,海正力星验证批样品状况,原研品,原研品,海正力星,101101,101102,101103,E49601,E54349,装量差异,应符合规定,应符合规定,符合规定,符合规定,符合规定,符合规定,符合规定,细菌内毒素,应小于,1.75EU/mg,应小于,1.75EU/mg,符合规定,符合规定,符合规定,符合规定,符合规定,异常毒性,应符合规定,应符合规定,符合规定,符合规定,符合规定,符合规定,符合规定,二氯甲烷,不得超过,0.06%,不得超过,0.06%,/,/,/,/,/,有关物质,/,最大未知杂质,0.15%,未检出,未检出,未检出,0.03,0.04,/,差向异构体,2.5%,0.39%,0.32%,0.32%,1.4,1.5,/,9-,氨基米诺环素,0.5%,未检出,未检出,未检出,0.06,0.07,/,9-,硝,基米诺环素,0.5%,未检出,未检出,未检出,0.03,0.03,/,米诺环素,0.5%,未检出,未检出,未检出,0.05,0.07,/,总杂质,3.0%,0.39%,0.32%,0.32%,1.5%,1.7%,含量（,%,）,按平均装量计算，含替加环素应为标示量的,96.0%,116.0%,按平均装量计算，含替加环素应为标示量的,96.0%,116.0%,107.1,105.2,105.3,105.1,/,海正力星与,原研品（,泰阁,）,质量一致性比较,40,50,株耐药菌替加环素,MIC,对照结果,(ug/ml),细菌,菌株编号,折点,(,FDA),海正力星,泰阁,MRSA,3323,0.5,0.125,S,0.06,S,MRSA,3651,0.125,S,0.125,S,MRSA,3667,0.06,S,0.06,S,MRSA,4123,0.125,S,0.125,S,MRSA,4124,0.06,S,0.06,S,MRSA,4128,0.125,S,0.125,S,MRSA,4150,0.06,S,0.06,S,MRSA,4700,0.125,S,0.125,S,MRSA,4834,0.06,S,0.06,S,MRSA,4852,0.06,S,0.06,S,ESBL+,大肠埃希菌,4037,0.5,4,R,4,R,ESBL+,大肠埃希菌,4052,0.06,S,0.06,S,ESBL+,大肠埃希菌,4106,0.06,S,0.06,S,ESBL+,大肠埃希菌,4107,0.06,S,0.06,S,ESBL+,大肠埃希菌,4111,0.06,S,0.06,S,ESBL+,大肠埃希菌,4417,0.06,S,0.06,S,ESBL+,大肠埃希菌,4419,0.06,S,0.06,S,ESBL+,大肠埃希菌,4028,0.06,S,0.06,S,ESBL+,大肠埃希菌,4047,0.06,S,0.06,S,ESBL+,大肠埃希菌,4055,0.06,S,0.06,S,数据来源：肖永红 国家传染病重点试验室,41,50,株耐药菌替加环素,MIC,对照结果,(ug/ml),细菌,菌株编号,折点,(,FDA),海正力星,泰阁,VRE,屎肠球菌,6465,0.064,0.06,S,0.06,S,VRE,屎肠球菌,7725,0.06,S,0.06,S,VRE,屎肠球菌,132,0.06,S,0.06,S,VRE,屎肠球菌,186,0.06,S,0.06,S,VRE,屎肠球菌,513,0.06,S,0.06,S,屎肠球菌,14103,0.06,S,0.06,S,屎肠球菌,3982,0.06,S,0.06,S,屎肠球菌,5518,0.06,S,0.06,S,粪肠球菌,5487,0.125,0.06,S,0.06,S,粪肠球菌,5497,0.06,S,0.06,S,ESBL+,肺炎克雷伯菌,3863,2,4,R,4,R,ESBL+,肺炎克雷伯菌,3866,0.125,S,0.125,S,ESBL+,肺炎克雷伯菌,4046,4,R,4,R,ESBL+,肺炎克雷伯菌,4049,1,S,0.5,S,ESBL+,肺炎克雷伯菌,4103,0.25,S,0.25,S,ESBL+,肺炎克雷伯菌,4389,2,S,2,S,ESBL+,肺炎克雷伯菌,4451,0.25,S,0.25,S,ESBL+,肺炎克雷伯菌,4455,2,S,2,S,ESBL+,肺炎克雷伯菌,5433,1,S,1,S,ESBL+,肺炎克雷伯菌,5434,1,S,1,S,数据来源：肖永红 国家传染病重点试验室,42,50,株耐药菌替加环素,MIC,对照结果,(ug/ml),细菌,菌株编号,折点,(,FDA),海正力星,泰阁,碳青霉烯类耐药鲍曼不动杆菌,7917,2,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7918,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7944,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7948,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7953,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7954,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7978,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7955,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7965,0.25,S,0.25,S,碳青霉烯类耐药鲍曼不动杆菌,7966,0.25,S,0.25,S,数据来源：肖永红 国家传染病重点试验室,43,小 结,替加环素：第一个甘氨酰环素类抗生素,广泛分布于人体各组织，组织浓度高,广谱覆盖耐药,G,-,菌、耐药,G,+,菌、厌氧菌和非典型病原体,有效治疗,cIAI,、,CAP,、,cSSSI,，临床治愈率和细菌清除率高,安全性良好,海正力星与原研替加环素相当,44,Thank you,45,谢 谢！,放映结束,感谢各位的批评指导！,让我们共同进步,46,