复杂腹腔感染

,泰能,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,泰能,*,泰能,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,泰能,*,泰能,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,泰能,*,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,*,*,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,*,复杂腹腔感染,内容,概念,复杂腹腔感染常见病原菌,起始充分治疗的诊治策略,亚胺培南在腹腔感染的优势和安全性,概念,复杂性腹腔感染,(complicated intra,abdominal infections),感染致病菌,不仅累及空腔脏器，还,穿透原发受累的器官进入腹腔，引起腹膜炎或腹腔脓肿,属继发性腹腔感染范畴,并非单纯手术就能解决问题,对抗感染药物治疗有着更高的要求,常见的病症,弥漫性或局限性化脓性腹膜炎,阑尾穿孔或阑尾周围脓肿,胃十二指肠穿孔,24,小时内未手术者,外伤性小肠或结肠穿孔,24,小时内未手术者,非外伤性小肠或结肠穿孔,腹腔脓肿,腹部手术后腹腔内感染,胆道,正常无菌,大肠埃希菌,克雷伯菌属,肠球菌,近端小肠,大肠埃希菌,克雷伯菌属,乳杆菌属,链球菌,类白喉菌,肠球菌,远端小肠,脆弱拟杆菌,梭菌属,大肠埃希菌,肠杆菌属,克雷伯菌属,消化链球菌,肠球菌,结肠,拟杆菌属,梭菌属,大肠埃希菌,肠杆菌属,克雷伯菌属,消化链球菌,肠球菌,及许多其他菌,胃,链球菌,乳杆菌属,消化道常见病原体,常见腹腔感染类型的微生物学,常见感染类型,常见病原菌,胆囊炎,大肠杆菌、克雷伯杆菌、肠球菌,远端小肠穿孔所致的感染,大肠杆菌、克雷伯杆菌、脆弱类拟杆菌、梭菌属,近端小肠感染,大肠杆菌、克雷伯杆菌属、变形杆菌,阑尾炎,大肠杆菌、铜绿假单胞菌和厌氧菌,(,拟杆菌属,),脓肿,大肠杆菌、克雷伯杆菌属、肠球菌和脆弱拟杆菌,结肠来源导致腹腔感染,绝大多数为厌氧菌感染,医院获得性腹腔感染,更常见对铜绿假单胞菌、肠杆菌属等耐药菌株,Weigelt JA, et al. Cleveland Clinical Journal of Medicine, 2007, 30 (suppl. 4): s29-37.,Weigelt JA, et al. Cleveland Clinical Journal of Medicine, 2007, 30 (suppl. 4): s29-37.,复杂性腹腔感染,(IAIs),的微生物学特点,混合杆菌感染为特征,以肠杆菌科为主，大肠杆菌感染占多数,非发酵菌和厌氧菌感染比例增加,产,ESBL,的肺炎克雷伯杆菌和大肠杆菌比例升高,非发酵菌主要包括铜绿假单胞菌和不动杆菌,2009,年腹腔感染病原菌分布,SMART,中国研究，大肠杆菌位居,G,-,菌第一,检出率,(%),2002-2009,年大肠埃希菌对亚胺培南的接近,100%,敏感率,(%),TZP:,哌拉西林,/,他唑巴坦,Qiwen Yang et al. International Journal of Antimicrobial Agents.2010;36:507512,2002-2009,年腹腔感染,ESBL+,大肠杆菌感染率不断增加,产,ESBL,的菌株逐年增加,感染率,(%),SMART,中国研究,2009,年,ESBL+/ESBL-,大肠杆菌,药物敏感性监测结果,敏感率,(%),SMART,中国研究,ETP:,厄他培南,;IMP:,亚胺培南,;CPE:,头孢吡肟,;CFT:,头孢噻肟,;CFX:,头孢呋辛,;CAZ:,头孢他啶,;CAX:,头孢曲松,;A/S:,氨苄西林,/,舒巴坦,;P/T:,哌拉西林,/,他唑巴坦,;AK:,阿米卡星,;CP:,环丙沙星,;LVX:,左氧氟沙星,各种药物对,ESBL,细菌的覆盖,Eur Respir Rev 2007; 16: 103, 3339,抗菌药物,ESBL,AmpC,三代头孢菌素,-,-,头孢吡肟,-,+,氟喹诺酮类,+/-,+,哌拉西林,/,他唑巴坦,+/-,+/-,替加环素,+,+,碳青霉烯,+,+,ESBL:,超广谱,-,内酰胺酶；,AmpC:,氨苄西林耐药基因,C,_:,无效；,+,：有效；,+,：作用较好；,+:,作用最好；,+/-,：部分有效,2002-2009,年肺炎克雷伯菌连续药物敏感性,监测结果,敏感率,(%),TZP:,哌拉西林,/,他唑巴坦,Qiwen Yang et al. International Journal of Antimicrobial Agents.2010;36:507512,SMART,等研究总结,大肠杆菌、肺炎克雷伯杆菌、铜绿假单胞菌依次为腹腔感染最常见致病菌,连续药敏监测结果显示，,腹腔感染主要致病菌对亚胺培南敏感性高,产,ESBL,大肠杆菌和肺炎克雷伯杆菌的耐药菌株不断增加，但对亚胺培南耐药率并未明显增加，,对亚胺培南仍保持较高敏感性,复杂性腹腔感染,(IAIs),抗感染药物选用指南,美国感染病学会,(IDSA),推荐,Solomkin JS, et al. Clinical Infectious Diseases. 2003;37:997-1005.,抗生素治疗开始的时间,一旦拟诊腹腔感染，伴全身和局部炎症反应,立刻开始抗生素治疗,治疗一定不能延迟到,正确的诊断成立,可用的培养结果,不用抗生素或初始治疗不恰当,治疗无效,死亡率,Solomkin JS, Mazuski JE, Baron EJ, et al. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis 2003; 37:9971005,Tellado JM, Sen SS, Caloto MT, et al. Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain. Scand J Infect Dis. 2007;39(11-12):947-55.,亚胺培南早期治疗腹腔感染可显著降低再次入院率,出院后,30,天内再次入院率,IAIs用药建议IDSA指南,2003,版,2010,版,轻,-,中度复杂性腹腔感染,重度复杂性腹腔感染,单一用药,氨苄西林,/,舒巴坦,替卡西林,/,克拉维酸,厄他培南,哌拉西林,/,他唑巴坦,亚胺培南,/,西司他丁,美罗培南,联合用药,头孢唑啉，头孢呋辛,+,甲硝唑,环丙沙星，莫西沙星，加替沙星或左氧氟沙星,+,甲硝唑,头孢吡肟，头孢他啶，头孢噻肟，头孢曲松，头孢唑肟,+,甲硝唑,环丙沙星,+,甲硝唑,氨曲南,+,甲硝唑,Solomkin JS, et al. Clinical Infectious Diseases. 2010; 50:13364.,+,莫西沙星,+,替加环素,+,头孢西丁,+,多利培南,+,头孢曲松,+,头孢噻肟,+,左氧氟沙星,2010,IDSA,指南,医院获得性腹腔感染,HI,感染的病原体,经验性抗菌治疗推荐方案,碳青霉烯类*,哌拉西林,-,他唑巴坦,头孢他啶,/,头孢吡肟,+,甲硝唑,氨基糖苷类,万古霉素,铜绿假单胞菌耐药菌株,20%,推荐,推荐,不推荐,推荐,不推荐,MRSA,不推荐,不推荐,不推荐,不推荐,推荐,Solomkin JS, et al. Clinical Infectious Diseases. 2010; 50:13364,.,无法确诊单一病原菌或怀疑混合感染时，亚胺培南整体敏感率高,肖永红,.,王进等,.,天津科学技术出版社,.2008:24-27,大肠埃希菌,(n=20987),肺炎克雷伯菌,(n=10533),阴沟肠杆菌,(n=4157),铜绿假单胞菌,(n=13720),鲍曼不动杆菌,(n=7613),亚胺培南,99.5,99.1,98.8,64.3,75.3,氨苄西林,/,舒巴坦,26.3,44.3,15.6,哌拉西林,/,他唑巴坦,81.2,70.2,63.7,67.5,41.0,头孢呋辛,34.5,49.7,25.5,头孢曲松,39.2,52.9,32.9,头孢他啶,74.3,72.0,53.6,63.9,38.8,头孢哌酮,/,舒巴坦,80.3,78.1,69.5,58.4,67.6,头孢吡肟,61.3,73.7,67.9,64.4,43.0,卫生部全国细菌耐药监测,(Mohnarin)2006-2007,年度报告,(,敏感率,%),腹腔感染的抗生素选择标准的变化,既往,重视两联和三联抗生素治疗,如 氨基糖苷类,/,-,内酰胺类,/,克林霉素,覆盖一系列可能的病原菌,近些年来,亚胺培南单药治疗已成为新的金标准,对预期的病原菌有 广谱的抗菌活性,安全性相对较好,使用方便,JOHN A. WEIGELT. Empiric treatment options in the management of complicated intra-abdominal infections CLEVELAND CLINIC JOURNAL OF MEDICINE 74 SUP 4 S29-37,亚胺培南组织浓度分布,亚胺培南注射后,2 h,在腹膜、胸膜中浓度最高,From FDA,亚胺培南治疗腹腔感染临床有效率,作者,(,年份,),亚胺培南病例数,/,总病例数,亚胺培南,剂量,/,静滴,临床有效率,细菌清除率,G.Zaetti .,(1999),79/161,0.5g q6h,93.8%,-,Philip S.(1997),122/217,0.5g q6h,76%,76%,Brismar(1995),117/249,0.5g q8h,96%,96%,Basoli A.(1997),139/287,1.5g/d,98%,95%,Bartoloni A.(1999),66/144,1g q12h,90.9%,92.9%,Marianne H.A(1996),258/515,1.5-2.0g/d,80.8%,86.9%,1.Journal of Antimicrobial Agents 11(1999)107-113,2.Arch Surg.1997;132:1294-1302.,3.Antimicrobial Chemotherapy(1995)35,139-148,4.Scand J Infect Dis 29:503-508,1997.,5.Drugs exptl clin res xxv(6) 243-252(1999),6.Scand J Infect Dis 28:513-518(1996),与美罗培南相比，,亚胺培南,退热,时间快天， 疗程短天,Basoli A et al.,Scand J Infect Dis. 1997;29(5):503-8.,亚胺培南天退热更快、疗程更短,在,287,例腹腔感染患者中进行的一项开放性、前瞻性、随机、平行、多中心研究，评估亚胺培南与美罗培南治疗腹腔感染的疗效和安全性,平均退热时间,(,天,),平均治疗时间,(,天,),n=101,n=100,n=101,n=100,P=0.046,P=0.019,退热更快,疗程更短,对,7,项开放研究,(,共,2096,例患者,),中美罗培南与,亚胺培南,治疗细菌感染耐受性比较的综述分析,Norrby SR, et al. J Antimicrob Chemother. 1995;36 Suppl A:207-23.,亚胺培南治疗中，肾毒性发生率低,发生率,亚胺培南治疗中,癫痫发生率,为,0.4%,摘自,PDR,，,PDR=Physician Desk Reference,全美医生常用手册,1.Data on file. MSD WPC.,2,. PRIMAXIN I.V.(imipenem and cilastatin for injection) prescribing information. Physicians Desk reference. 55th ed. Montvale, NJ, USA:Medical Economics Company, 2001.,3,. MERREM I.V.(meropenem for injection) prescribing information. Physicians Desk reference. 55th ed. Montvale, NJ, USA:Medical Economics Company, 2001.,4,. PRIMAXIN I.V.(imipenem and cilastatin for injection) prescribing information. Physicians Desk reference. 56th ed. Montvale, NJ, USA:Medical Economics Company, 2002.,5,. MERREM I.V.(meropenem for injection) prescribing information. Physicians Desk reference. 56th ed. Montvale, NJ, USA:Medical Economics Company, 2002.,6,. PRIMAXIN I.V.(imipenem and cilastatin for injection) prescribing information. Physicians Desk reference. 57th ed. Montvale, NJ, USA:Medical Economics Company, 2003.,7. MERREM I.V.(meropenem for injection) prescribing information. Physicians Desk reference. 57th ed. Montvale, NJ, USA:Medical Economics Company, 2003.,8. PRIMAXIN I.V.(imipenem and cilastatin for injection) prescribing information. Physicians Desk reference. 58th ed. Montvale, NJ, USA:Medical Economics Company, 2004.,9.,MERREM I.V.(meropenem for injection) prescribing information. Physicians Desk reference. 58th ed. Montvale, NJ, USA:Medical Economics Company, 2004.,10.,PRIMAXIN I.V.(imipenem and cilastatin for injection) prescribing information. Physicians Desk reference. 59th ed. Montvale, NJ, USA:Medical Economics Company, 2005.,11,. MERREM I.V.(meropenem for injection) prescribing information. Physicians Desk reference. 59th ed. Montvale, NJ, USA:Medical Economics Company, 2005.,12,. PRIMAXIN I.V.(imipenem and cilastatin for injection) prescribing information. Physicians Desk reference. 60th ed. Montvale, NJ, USA:Medical Economics Company, 2006.,13.,MERREM I.V.(meropenem for injection) prescribing information. Physicians Desk reference. 60th ed. Montvale, NJ, USA:Medical Economics Company, 2006.,亚胺培南,治疗,1,723,例患者的癫痫发生率,亚胺培南,2001,PDR,2002,PDR,2003,PDR,2004,PDR,2005,PDR,2006,PDR,替加环素与亚胺培南治疗复杂腹腔感染的疗效和安全性对比,Chen et al. BMC Infectious Diseases 2010, 10:217,替加环素中国注册临床：,参加这个研究的专家：陈长青、吴菊芳、张婴元、韦军民、冷希圣、严律南、全智伟、陈孝平、俞云松、吴志勇、刘大为、马晓春、,研究人群及患者分布,入选人群,=203,随机,ITT,人群,=203,；亚胺培南,=104,替加环素,=99,mITT,人群,=199,；亚胺培南,=102,替加环素,=97,c-mITT,人群,=195,；亚胺培南,=98,替加环素,=97,CE,人群,=164,；亚胺培南,=87,，替加环素,=77,m-mITT,人群,=115,；亚胺培南,=55,替加环素,=60,ME,人群,=100,；亚胺培南,=48,，替加环素,=52,4,例患者未接受受试药物治疗,4,例患者不符合疾病最低标准,80,例患者未检出基础分离株,64,例患者未检出基础分离株或敏感菌株,31,例患者不符合评估标准,Zhangjing Chen et al. BMC Infectious Diseases 2010, 10:217,意向治疗,(ITT),人群：符合入选和排除标准的所有患者；修正意向治疗,(mITT),人群 ：至少接受过一种受试药物的,ITT,患者；,临床修正意向治疗,(c-mITT),人群：,符合最低疾病入选标准，临床证据显示有,cIAIs,的,mITT,患者；,微生物修正意向治疗,(m-mITT),人群：,至少检出,1,种基础分离株的,mITT,患者；临床可评估,(CE),人群：接受足够剂量,(,至少治疗,5,天，给药剂量为计划给药剂量的,80-120%),受试药物治疗，研究期间未使用其他抗菌药物，给药后,12-37,天进行治愈率评估的,c-mITT,患者；微生物学可评估,(ME),人群 ：至少检出,1,种对受试药物敏感且出现微生物学应答基础分离株的,CE,人群,亚胺培南与替加环素治疗,cIAIs,的疗效对比,临床治愈率,亚胺培南治疗,cIAIs,的临床治愈率达,90-98%(vs,替加环素,80-87%),78/97,88/98,67/77,83/87,49/60,50/55,45/52,47/48,Zhangjing Chen et al. BMC Infectious Diseases 2010, 10:217,亚胺培南与替加环素治疗,cIAIs,的细菌清除率对比,细菌清除率,30/33,25/26,15/19,22/22,Zhangjing Chen et al. BMC Infectious Diseases 2010, 10:217,替加环素比亚胺培南治疗,cIAIs,的细菌清除率,总病原体感染低,11%,，特别值得关注的是混合感染低,22%,IAI临床治愈率比较，亚胺培南更高,Zhangjing Chen et al. BMC Infectious Diseases 2010, 10:217,替加环素,亚胺培南,差异,替加环素,-,亚胺培南,人群,N,% (95% CI),N,% (95% CI),% (95% CI),ME,45/52,86.5,(74.2, 94.4),47/48,97.9,(88.9, 99.9),-11.4,(-23.5, 0.7),单一病原体感染,30/33,90.9,(75.7, 98.1),25/26,96.2,(80.4, 99.9),-5.2,(-22.0, 13.7),混合感染,15/19,78.9,(54.4, 93.9),22/22,100.0,(84.6, 100.0),-21.1,(-46.1, 2.2),m-mITT,49/60,81.7,(69.6, 90.5),50/55,90.9,(80.0, 97.0),-9.2,(-23.4, 4.9),单一病原体感染,32/38,84.2,(68.7, 94.0),27/29,93.1,(77.2, 99.2),-8.9,(-26.0, 10.7),混合感染,17/22,77.3,(54.6, 92.2),23/26,88.5,(69.8, 97.6),-11.2,(-35.8, 13.0),CE,67/77,87.0,(77.4, 93.6),83/87,95.4,(88.6, 98.7),-8.4,(-18.3, 1.5),c-mITT,78/97,80.4,(71.1, 87.8),88/98,89.8,(82.0, 95.0),-9.4,(-20.3, 1.6),治疗,cIAI,亚胺培南比替加环素不良事件发生率低,不良事件发生率,亚胺培南治疗的患者不良事件的发生率显著低于替加环素,Zhangjing Chen et al. BMC Infectious Diseases 2010, 10:217,哌拉西林,-,三唑巴坦,4.5g q6h,头孢他啶,2g q8h,头孢吡肟,2g q812h,庆大霉素,7mg/kg/d,妥布霉素,7mg/kg/d,阿米卡星,20mg/kg/d,亚胺培南,0.5g q6h,或,1.0g q8h,美罗培南,1.0g q8h,环丙沙星,400mg q8h,左氧氟沙星,750mg qd,万古霉素,15mg/kg q12h,利奈唑胺,15mg/kg q12h600mg q12h,对于肾功能正常的患者，合适的静滴剂量,:,Am J Respit Crit Care Med.2005;17(4):388-416,谢 谢！,The End,谢谢您的聆听！,期待您的指正！,