中心粒细胞减少患者的感染与经验治疗.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,*,中性粒细胞减少患者的 感染与经验治疗,1,1.,目前,MRS,是中性粒细胞感染患者主要的致病菌,2,中性粒细胞减少常继发感染,1,50%,的中性粒细胞减少伴发热患者发生感染,（有或没有明确病原）,1/15,中性粒细胞减少患者（,100/mm,3,）发生菌血症,1,、,Hughes WT et al.2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer,Clin Infect Dis,2002;34:730-51,3,中性粒细胞减少发生感染的危度,2,2,、,PicazoJJ.Management of the febrile neutropenic patients.,Intl J Antimicrob Agent,2005;26S:S120-S122,发生粒细胞减少的时间（周）,%,感染发生的危险,4,血 液 科 感 染 病 原 菌 标 本 来 源,-,北美中性粒细胞减少化疗及细菌耐药控制协作组,(CANCER),报告,3,3,、,JMILaboratories.Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients:Report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program(North America).,Diagn Microbiol Infect Dis,2006;56:75-82.,血标本,64.5%,尿标本,12.6%,皮肤软组织,11.9%,呼吸道,9.4%,其它,1.6%,5,血液科感染10,种常见病原菌,-,北美中性粒细胞减少化疗及细菌耐药控制协作组,(CANCER),报告,4,4,、,JMILaboratories.Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients:Report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program(North America).,Diagn Microbiol Infect Dis,2006;56:75-82.,G+:50.6%,G-:37.9%,0.0%,5.0%,10.0%,15.0%,20.0%,25.0%,金葡菌,凝固酶阴性葡萄球菌,肠球菌,非肺链球菌,肺炎链球菌,大肠杆菌,克雷伯菌,绿脓杆菌,肠杆菌,嗜麦芽窄食假单胞菌,6,血液病患者感染的常见病原菌,5,5,、朱骏，等,.,血液系统疾病患者中临床分离菌分布及耐药性分析,.,中国感染与化疗杂志,2006;6(1):37-41,160,株革兰阴性菌中所占的,%,195,株革兰阳性菌中所占的,%,7,血液病患者的葡萄球菌感染以耐药菌株为主,6,6,、朱骏，等,.,血液系统疾病患者中临床分离菌分布及耐药性分析,.,中国感染与化疗杂志,2006;6(1):37-41,8,萄葡球菌对甲氧西林耐药的含义,葡萄球菌（包括金葡菌和凝固酶阴性葡萄球菌）对甲氧西林耐药，其含义是：,对所有,-,内酰胺类抗生素耐药,对绝大多数大环内酯类、氟喹诺酮类、氨基糖苷类等同时耐药,治疗药物应首选糖肽类抗生素,9,2.,国内葡萄球菌对稳可信始终保持,100%,的敏感率,10,目前常用的多种抗生素对,MRS,耐药严重,7,200,5-2006,国内5,9,家三级甲等医院,多重耐药葡萄球菌对,9,种常用抗生素的敏感率,7,、,20052006,年,国家细菌耐药性监测中心监测数据总结,敏感率,0%,0%,11%,25%,26%,51%,50%,77%,13%,34%,3%,3%,9%,26%,95%,93%,100%,100%,0%,10%,20%,30%,40%,50%,60%,70%,80%,90%,100%,青霉素,G,克林霉素,阿米卡星,利福平,庆大霉素,阿齐霉素,左氧氟沙星,替考拉宁,万古霉素,MRSA,MRCNS,11,3.,稳可信是治疗,MRS,感染的一线用药,12,粒细胞减少患者感染的特点,病情凶险，死亡率高,感染易扩散，败血症、肺炎等严重感染,发生率高，混合感染多,临床表现常不典型，不易形成局部化脓病灶,常规抗菌治疗效果差,13,稳可信,治疗,MRS,的卓越临床疗效,作者,疾病,病例数,临床疗效,Levine,8,心内膜炎,17,82%,Myers,9,菌血症,15,87%,Craven,10,菌血症,19,74%,Coppens,11,菌血症,8,88%,Cafferkey,12,伤口感染/骨髓炎,19,89%,Cafferkey,13,肺部感染,7,86%,Menichetti,14,中性粒细胞减少性发热,252,75%,DAntonio,15,菌血症(中性粒细胞减少性发热),61,92,%,8、Ann Intern Med 1982;97:330.9、J Infect Dis 1982;145:532.10、J Infect Dis 1983;147:137.,11、Antimicrob Agents Chemother 1983;23:36.12、J Antimicrob Chemother 1982;9:69.13.Scand J Infect Dis 1988;20:297-301.,14.Antimicrob Agents Chemother 1994;38(9):2041-6 15.Chemotherapy 2004;50(2):81-7,14,替考拉宁治疗重症感染的疗效,资料来源,疾病,剂量,/,天,病例数,有效率,Calain P,16,金葡菌,菌血症,3 mg/kg,6,50%,Lerner,17,金葡菌,菌血症,6 mg/kg,9,100%,USA-1,17,金葡菌,菌血症,6 mg/kg,60,80.0%,USA-2,17,金葡菌,菌血症,6 mg/kg,14,21.4%,USA-3,17,金葡菌,菌血症,30 mg/kg,49,85.7%,Liu,18,金葡菌,菌血症,6 mg/kg,20,85.0%,16 J Infect Dis 1987;155(2):187-91 17 Int J Antimicrob Agents 1994;4(Suppl 1):S1-S30 18 Clin Drug Invest 1996;12:80-7,15,万古霉素经验治疗指征,-,IDSA,指南,19,临床上怀疑严重导管相关感染,细菌培养证实存在青霉素及头孢菌素耐药的,链球菌或,MRSA,的定植,血培养发现革兰阳性球菌,低血压或有其他证据提示有心血管系统受损者,19,、,Hughes WT et al.2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer,Clin Infect Dis,2002;34:730-51,16,万古霉素联合用药,严重的感染往往需要及时经验用药,而适当的联合,经验用药可以大大提高临床有效率,17,联合万古霉素治疗中性粒细胞 减少方案疗效更好,分组,(,粒细胞绝对数,),碳青霉烯类,+,万古霉素,碳青霉烯类,头孢菌素,/,喹诺酮类,治疗有效率,0.5,90.0,20,60.0,27.0,1.0,93.0,20,70.0,40.0,平均疗程,(d),7.32.1,9.53.1,14.65.4,20,、与其它两组比较,P95%,(1986,年,),离子交换树脂解析法提纯,纯度为,75%,(1960,年,),稳可信,层析纯化万古霉素,欧洲药典规定：万古霉素的纯度不得低于,93%,26,稳可信,纯度96.7%,去甲万古纯度仅为90%,稳可信,层析纯化万古霉素,24,24,、中国药品生物制品检定所 1994.11.28,27,由于,稳可信,制剂纯度的显著提高，过去低纯度,万古霉素的肾毒性已很少发生,25,高纯度,稳可信,能很好耐受，极少发生不良反。,偶尔出现的肾毒性和耳毒性都是可逆的,25,26,25,、,Eng et al,Chemother 1989;35(5):320325.,26,、,Wenman et al,Agent and Chemother.Sep.29Oct.22,1991.,稳可信,高纯度、更高的安全性,28,-肾功能正常病人：,成人：2,g/,天，,500mg/6,小时或1,g/12,小时,儿童：40,mg/kg/,天，分2-4次静滴,新生儿 10 15,mg/kg,出生1周内，每12小时一次,出生1周到一月，每8小时一次,-老年人：,500mg/12,小时或 1,g/24,小时,稳可信,剂量及用法,29,肾功能异常病人剂量调整方法,肌酐值以,mol/L,表示时，,K=0.814,肌酐值以,mg/dL,表示，,K=72,本公式应用于女性值，求得值需乘以,0.85,首次负荷剂量,:15mg/kg,(,),血清肌酐值,年龄,）,肌酐清除率（,-,=,K,kg,ml,140,min/,/,30,剂量调整例子,某男性病人,65,岁，体重为,70kg,血肌酐值为,160,mol/L,该病人每日稳可信的给药总量为,9.3,70=651mg,(,),6,.,0,160,814,.,0,65,140,k,min/,/,=,-,=,）,肌酐清除率（,g,ml,31,稳可信稀释后静脉滴注,药物浓度不超过 5毫克/毫升,每次滴注时间应该超过 60分钟,肾功能损害及年长患者应调整剂量,必要时监测血药浓度,经常改变输注部位,稳可信,应用准则,32,参 考 文 献,1,、,Hughes WT et al.2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer,Clin Infect Dis,2002;34:730-51,2,、,PicazoJJ.Management of the febrile neutropenic patients.,Intl J Antimicrob Agent,2005;26S:S120-S122,3,、,JMILaboratories.Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients:Report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program(North America).,Diagn Microbiol Infect Dis,2006;56:75-82.,4,、,JMILaboratories.Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients:Report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program(North America).,Diagn Microbiol Infect Dis,2006;56:75-82.,33,5,、朱骏，等,.,血液系统疾病患者中临床分离菌分布及耐药性分析,.,中国感染与化疗杂志,2006;6(1):37-41,6,、朱骏，等,.,血液系统疾病患者中临床分离菌分布及耐药性分析,.,中国感染与化疗杂志,2006;6(1):37-41,7,、,2005-2006,年国家细菌耐药性监测中心监测数据总结,8、Ann Intern Med 1982;97:330.,9、J Infect Dis 1982;145:532.,10、J Infect Dis 1983;147:137.,11、Antimicrob Agents Chemother 1983;23:36.,12、J Antimicrob Chemother 1982;9:69.,13.Scand J Infect Dis 1988;20:297-301.,Antimicrob Agents Chemother 1994;38(9):2041-6,15.Chemotherapy 2004;50(2):81-7,16 J Infect Dis 1987;155(2):187-91,17 Int J Antimicrob Agents 1994;4(Suppl 1):S1-S30,18 Clin Drug Invest 1996;12:80-7,参 考 文 献,34,参 考 文 献,19,、,Hughes WT et al.2002 Guidelines for the Use of Antimicrobial Agents in,Neutropenic Patients with Cancer,Clin Infect Dis,2002;34:730-51,20,、与其它两组比较,P0.05,段连宁等,.,联合应用抗生素对中性粒细胞减少期感染的经验治疗,.,中华医院感染学杂志,2006;16(1):79-82,21,、,Harter C,et al.Piperacillin/tazobactam vs ceftazidime in the treatment of neutropenic fever in patients,with acute leukemia or following autologous peripheral blood stem cell transplantation:a prospective randomized trial.,Bone Marrow Transplantation,2006;37,（,4,）,:3739,22,、,DAntonio D,et al.Addition of teicoplanin or vancomycin for the treatment of documented bacteremia,due to Gram-positive cocci in neutropenia patients with hemalogical malignancies:microbiological,clinical and economic evaluation.Chemotherapy 2004;50:81-87,23,：两组比较,P=0.013,DAntonio D,et al.Addition of teicoplanin or vancomycin for the treatment of documented bacteremia due,to Gram-positive cocci in neutropenia patients with hemalogical malignancies:microbiological,clinical and economic evaluation.Chemotherapy 2004;50:81-87,35,24,、中国药品生物制品检定所 1994.11.28,25,、,Eng et al,Chemother 1989;35(5):320325.,26,、,Wenman et al,Agent and Chemother.Sep.29Oct.22,1991.,36,