真菌-药敏折点.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,*,真菌实验室诊断进展,-,敏感试验结果的解释,北京协和医院检验科,徐英春,氟康唑,5-,氟胞嘧啶,伊曲康唑,#,两性霉素,B*,伏立康唑,v,S,8,4,0.125,0.5,1,SDD 16-32 -,0.25-0.5,-,2,I -8-16,-,-,R,64,32,1,1,4,酵母菌的,NCCLS M27-A,1997,抗真菌药物的判定折点,#,粘膜中酵母菌；*非,NCCLS,标准,;CLSI,未公布对念珠菌的折点,纸片扩散法敏感试验,的判定标准,氟康唑,mm,伏立康唑,mm,S:,敏感,19,17,SDD:,剂量依赖敏感,15-18,14-16,R:,耐药,14,13,S,Susceptible SDD=Susceptible,-,Dose Dependent R=Resistant,读取抑菌环直径近似到,mm,在大约,80%,抑制区为测量边界,在抑菌环内个别细小或中等大小的菌落不计,M44-P,纸片扩散法,药敏结果判定,体外抗真菌药敏试验指导用药,以氟康唑为例：,MIC,剂量,4,g/ml 100mg/d,4-8,g/ml 200mg/d,8-16,g/ml 400mg/d,16-32,g/ml 800mg/d,Hopenthal,et al,Diagn,Microb,Infect,Dis,2004,48:153-160,氟康唑的,MIC,折点与临床的关系,692,例 粘膜 念珠菌,603,例 侵袭性念珠菌,MIC,（,ug,/ml),(n),(n),8,77(533)76(460),16-32 8(58)12(72),64,15(101),12(71),Pfaller,M,Diekema,D,，,Sheehan D.,Clin,Micro REV,，,In Press,，,2006,氟康唑的敏感性与念珠菌感染治疗的临床有效率,感染类型,例数,SSDDR,粘膜,692 92,62,41,(488/533)(36/58)(41/101),侵袭性,603 77,71,44,(353/460)(51/72)(31/71),合计,1295,85,67,42,(841/993)(87/130)(72/172),Pfaller,M,Diekema,D,，,Sheehan D.,Clin,Micro REV,，,In Press,，,2006,氟康唑念珠菌的药敏,折点适合粘膜感染、侵袭性念珠菌感染,SDD,：高剂量，疗效接近,S,SDD,：成功率高于,R,菌株,体外抗真菌药敏试验与体内疗效,NCCLS M27-A,600,余株念珠菌,MIC,值：分离自,150,余例,AIDS,的食管念珠菌病，一致性好；治疗失败者，,MIC,值大于,64,g/ml,90-60,原则,MIC,值与临床疗效,药敏试验敏感菌株：,90%,对治疗有效,药敏试验耐药菌株：,60%,对治疗有效,Mahmoud,A.G,JCM 1996,34:489-495,；,Rex J,CID 2002,35:982-989,常见的念珠菌体外敏感性评估：,S=,敏感,S-DD=,剂量依赖敏感,I=,中介,R=,耐药,Pappas PG et al,Clin,Infect,Dis,2004;38:161-89;,Bartizal,K et al,Antimicrob,Agents,Chemother,1997;41:2326-32;Patterson TF.,J,Chemother,1999;11:504-12;,Pfaller,MA et al,Antimicrob,Agents,Chemother,2002;46:1723-7;,Pfaller,MA et al,J,Clin,Microbiol,2002;40:852-6,菌株,氟康唑,伊曲康唑,两性霉素,伏立康唑,泊沙康唑,卡泊芬净,白念珠菌,S,S,S,S,S,S,热带念珠菌,S,S,S,S,S,S,近平滑念珠菌,S,S,S,S,S,S,/,I?,都伯林念珠菌,S,/,S-DD,S,S,/,I,S,/,S-DD,S,/,S-DD,S,光滑念珠菌,S-DD,/,R,S-DD,/,R,S,/,I,S,/,S-DD,S,/,S-DD,S,克柔念珠菌,R,S-DD,/,R,S,S,S,S,葡萄牙念珠菌,S,S,S,/,R,S,S,S,抗真菌药物在体外对真菌病原学活性,真菌,氟康唑,伏立康唑,泊沙康唑,棘白菌素类,多烯类,白念珠菌,+,+,+,+,+,光滑念珠菌,+/-,+,+,+,+,热带念珠菌,+,+,+,+,+,近平滑念珠菌,+,+,+,+,（高,MIC,）,+,克柔念珠菌,+,+,+,+,季也蒙念珠菌,+,+,+,+(,高,MIC),+,新型隐球菌,+,+,+,+,无活性；,+/,可能有活性；,+,有活性，三线（至少临床有效）,+,有活性，二线（作用稍差）；,+,有活性，一线（常常有效）,热病,37,th,Edition 2007,曲霉的药敏感试验与临床疗效,Aspergillus,spp,from 29 patients with IA,黄曲霉,A.,flavus,41%,土曲霉,A.,terreus,31%,烟曲霉,A.,fumigatus,28%,A.,terreus,MIC was consistently high,Pts with isolates with MIC 2,ug,/ml died,Lass,FlorIC,，,JAC 1998,抗真菌药物在体外对真菌病原学活性,真菌,氟康唑,伏立康唑,泊沙康唑,棘白菌素类,多烯类,烟曲霉,+,+,+,+,黄曲霉,+,+,+,+,（高,MIC,）,土曲霉,+,+,+,镰刀霉,+,+,+,（脂质）,尖端赛多孢,+,+,+/,+/,多育赛多孢,+/,+/,+/,犁头霉毛霉根霉,+,+,（脂质）,无活性；,+/,可能有活性；,+,有活性，三线（至少临床有效）,+,有活性，二线（作用稍差）；,+,有活性，一线（常常有效）,热病,37,th,Edition 2007,抗真菌药物在体外对真菌病原学活性,无活性；,+/,可能有活性；,+,有活性，三线（至少临床有效）,+,有活性，二线（作用稍差）；,+,有活性，一线（常常有效）,真菌,氟康唑,伏立康唑,泊沙康唑,棘白菌素类,多烯类,暗色真菌：链格孢、离蠕孢、,+,+,弯孢霉属、外瓶霉 等,+/,+,+,+,+,双相真菌：,皮炎芽生菌,+,+,+,+,+,粗球孢子菌,+,+,+,+,荚膜组织胞浆菌,+,+,+,+,申克孢子丝菌,+,+,+,+,热病,37,th,Edition 2007,结论,MIC,的价值，不一定能预测临床治疗的结果,棘白菌素类、伏立康唑、泊沙康唑和多烯类尿中浓度低,严重免疫抑制,/,低下者，治疗成功需要免疫重建,氟胞嘧啶对念珠菌、隐球菌、暗色真菌有活性，但初始治疗用于联合用药,念珠菌出现继发感染，以前用过三唑类，很可能对三唑类耐药,对近平滑念珠菌感染治疗成功，清除异物拔出导管,结论,脂质体两性霉素,B,对烟曲霉和黄曲霉的活性强 （,+,）,多育赛多孢需要联合治疗（如联用特比奈芬）,接合菌、某些曲霉、暗色真菌常需手术切除病灶,对于双向真菌，伊曲康唑一线用药临床有效（,+,）,