不动杆菌流行及治疗.ppt

不动杆菌流行及治疗不动杆菌流行及治疗 福建医科大学附属第一医院福建医科大学附属第一医院 呼吸内科呼吸内科 林晓林晓 不动杆菌 鲍曼不动杆菌（A baumanii）醋酸钙不动杆菌（A calcoacelicus）溶血性不动杆菌（A haemolyticus）不动杆菌为革兰氏染色阴性、无芽孢、两端钝圆、散在或个别成双排列、大小(0.61.0)m(1.01.6)m 的杆状(球杆状)细菌。临床标本中分离到的不动杆菌绝大数为鲍曼不动杆菌，其它菌种引起的感染比较少见。鲍曼不动杆菌占鲍曼不动杆菌占ICUICU院内获得性院内获得性肺炎病原菌的比肺炎病原菌的比例及对常用抗菌例及对常用抗菌药物的耐药率药物的耐药率Clin Infect Dis 2005:41:848-8542008年CHINET耐药监测革兰阴性菌菌种分布 细菌株数 细菌株数大肠埃希菌651226.58 莫拉菌属1410.58 铜绿假单胞菌403416.47 摩根菌属1360.56 克雷伯菌属371715.17 志贺菌属1300.53 不动杆菌属350814.32 产碱杆菌1080.44 肠杆菌属14165.78 沙门菌属990.40 嗜麦芽窄食单胞菌12745.20 罗尔斯顿菌属670.27 流感嗜血杆菌8123.31 气单胞菌属660.27 变形杆菌属6562.68 博特菌属350.14 其他嗜血杆菌2140.87 普罗威登菌属290.12 其他假单胞菌3441.40 奈瑟菌属250.10 沙雷菌属2711.11 多源菌属200.08 柠檬酸杆菌属2601.06 丛毛单胞菌140.06 伯克霍尔德菌属2360.96 黄杆菌属110.04 金杆菌属1660.68 其他1990.81 合计24500100.0Multidrug-resistant A.baumannii(MDRAB)Multidrug-resistant A.baumannii(MDRAB)Resistance to 3 or more than 3 kinds of Resistance to 3 or more than 3 kinds of antibioticsantibioticspantipseudomonal cephalosporinspantipseudomonal carbapenemsp-lactamase inhibitor combinationspantipseudomonal fluoroquinolonespaminoglycosidesPandrug-resistant A.baumannii,PDRABPandrug-resistant A.baumannii,PDRABlresistance to all antibiotics but polymycin and tigecyclineClin Microbiol Rev 2008;21:538-82N Engl J Med 2008;358:1271-81“XDR”：extreme drug resistance对抗绿脓的头孢菌素对抗绿脓的头孢菌素抗绿脓的碳青霉烯类抗绿脓的碳青霉烯类-内酰胺抗生素复合制剂内酰胺抗生素复合制剂氟喹诺酮类氟喹诺酮类氨基糖苷类氨基糖苷类替加环素替加环素多粘菌素多粘菌素 3个克隆在英国全国广泛流行6个主要克隆在6省市19家医院播散(342株）我国不同城市间出现相同克隆 为什么鲍曼不动杆菌会全球流行？广泛分布水、土壤、医院环境和人体皮肤表面强大的环境生存能力和广泛的耐药性使其成为越来越重要的院感病原菌近年，多重耐药鲍曼不动杆菌（MDR-AB）已经在全球各地出现甚至造成了爆发性流行，并且伴随着耐药性的不断增强 12强大的环境生存能力20-3020-30环境下生长良好，环境下生长良好，抵抗力强，抵抗力强，在干燥的物体表面在干燥的物体表面 鲍曼不动杆菌可存活鲍曼不动杆菌可存活2525天天 远远超过其他革兰阴性杆菌远远超过其他革兰阴性杆菌 强大的耐药基因获得能力Acinetobacter baylyi ADP1拥有比大肠杆菌感受态细胞强大100倍的捕获外源DNA能力错配修复系统mutS 的缺失增加了部分不动杆菌的突变频率OXA carbapenemases in A.baumannii获得性天然染色体介导OXA-51/69-likeOXA-23OXA-64OXA-24OXA-65OXA-25OXA-66OXA-26OXA-68OXA-40OXA-70OXA-58OXA-71OXA-78质粒介导OXA-79OXA-23OXA-80OXA-58OXA-82Perez F,et al.Antimicrob Agents Chemother 2007;51:3471-84.如何对付不动杆菌呢如何对付不动杆菌呢？消毒剂分类季铵盐类：低效，抗性多；双胍类：主要是醋酸氯己定，抗性普遍；酚类：酚可能造成环境污染，适用受限；醛类：主要在假单胞菌和肠杆菌科细菌有抗性报道 消毒剂分类卤素类：包括含氯消毒剂、含碘消毒剂和含溴消毒剂，对含碘消毒剂的抗性尚待确认；醇类：常用消毒剂，抗性也有报道；氧化剂类：过氧乙酸、高锰酸钾，是高效消毒剂；其他：如金属离子消毒剂，已较少使用未发现对消毒剂的抗性，也未发现抗生素耐未发现对消毒剂的抗性，也未发现抗生素耐药与消毒剂抗性之间的联系药与消毒剂抗性之间的联系对目前使用消毒剂耐药可能并不是目前鲍曼不动感觉流行播散的最重要原因消毒措施偏差所导致的浓度和暴露时间减少可能导致院内交叉感染的发生Contaminated surfaces increase cross-transmissionX X represents multi-drugs resistant pathogens culture positive sites无处不在！无处不在！Acinetobacter Transmission in the Hospital SettingnDirect or indirect contactnContaminated hands of healthcare workersnAirborne transmission via aerosol production(e.g.,hydrotherapy)may occurEnvironmental Contamination with AcinetobacternBed railsnBedside tablesnVentilatorsnInfusion pumpsnMattressesnPillowsnAir humidifersnPatient monitorsnX-ray view boxesnCurtain railsnCurtainsnEquipment cartsnSinksnVentilator circuitsnFloor mops抗生素的应用抗生素的应用？！？！Susceptiblity of A.baumannii:1994-2004(1874 isolates)Susceptibiligy(%)YearAntimicrobial Resistance among Acinetobacter sp.,From ICUs 1986-20032008年12家医院3508株不动杆菌属(鲍曼不动86.2%)细菌的耐药率（%）对头孢哌酮/舒巴坦耐药率较低。对其他药耐药率均较高。两种碳青霉烯类耐药率均48%，高于2007年。Major infections due to AcinetobacternVentilator-associated pneumonia nUrinary tractnBloodstream infection infectionnSecondary meningitisnSkin/wound infectionsnEndocarditisn peritonitisnEndophthalmitisHow to treat infections caused by MDR A.baumanniiSulbactam combinationsColistintigecycline%ofinhibited isolates concentration of sulbactamg/mlFASS RJ,et al.Antimicrobial agents and chemotherapy 1990;34(11):2256-2259.Activity of sulbactam to A.baumannii鲍曼不动杆菌体外药敏ampicillin/sulbactam to treat MDRAB infectionsbacteremia（13）pneumonia（12）Urinary infection（6）peritonitis（3）Wound infection（3）meningitis（2）sinusinfection（1）Effective%4675100100670100Levin et al.Int J Antimicrob Agents 2003;21:58-62CRAB治疗-含舒巴坦制剂对不动杆菌具有固有的抗菌活性.根据体外药敏实验结果选择用药.降低感染死亡率.国外报道对于严重感染者,舒巴坦的推荐剂量为6g/d,甚至在12g/d时仍有较好的安全性,但在治疗效果上与9g/d组并无统计学差异.Clin Microbiol Rev 2008:21:538-582.Lancet Infect Dis 2008:8:751-762.Scand J Infect Dis 2007:39:38-43.CRAB的治疗的治疗-多黏菌素多黏菌素静脉应用多黏菌素治疗总有效率为静脉应用多黏菌素治疗总有效率为57%80%.肾功能损害的发生率约为肾功能损害的发生率约为037%.雾化吸入有助于减少全身用药的副作用雾化吸入有助于减少全身用药的副作用,并在并在 局部组织达到较高的药物浓度局部组织达到较高的药物浓度.仍需进一步临床对照研究证实仍需进一步临床对照研究证实.Clin Microbiol Rev 2008:21:538-582.High resistance to colistin of MDRAB from Korea Considering theincreasing use of colistin,independent but frequent emergence of colistin resistance inMDRAB is of great concern.Kwan Soo Ko,JAC 2007,60:1163-7Young Kyoung Parka,DMID 2009,64:43-51BIG BIG BUG!BUG!Colistin Good outcome to MDR AB infection，including:bacteremia、pneumonia、urinary tract infection、wound infection、meningitisOnly 10.8 CRAB were resistant to colistin in China MainlandTigecycline:the saviour?22 microbiological studies reporting data for 2384 Acinetobacter spp,90%isolates(including MDR and CRAB)were susceptible42 severely ill patients,tigecycline therapy(combination with other antibiotics in 28 patients)was effective in 32 cases In 3 cases,resistance to tigecycline developed during treatment Drosos EK,et al.JAC,2008,62:44-45Tetracycline Susceptibility Testing in Isolates of Acinetobacte from a U.S.Military HospitalKevin S.Akers,AAC,2009,acceptedSusceptibility of 73 IPM-I or R A.baumannii isolates to tigecyclineS:6 isolatesS:6 isolates（8.28.2），），I:6 I:6 isolatesisolates（8.28.2），），R:61 R:61 isolatesisolates（83.683.6）Susceptibility of 43 IPM-S Susceptibility of 43 IPM-S Susceptibility of 43 IPM-S Susceptibility of 43 IPM-S A.baumanniiA.baumanniiA.baumanniiA.baumannii isolates to isolates to isolates to isolates to tigecyclinetigecyclinetigecyclinetigecyclineS:19 isolatesS:19 isolates（44.244.2），），I:6 I:6 isolatesisolates（14.014.0），），R:18 R:18 isolatesisolates（41.941.9）替加环素对中国部分地区亚胺培南耐药鲍曼不动替加环素对中国部分地区亚胺培南耐药鲍曼不动杆菌体外抗菌活性差杆菌体外抗菌活性差In vitro studiesAnimal modelsClinical experienceMP+SAMMP+SAMRIF+COIP+SAMIP+SAMCO+*RIF+SAMIP+TOBRIF+POIP+RIFRIF+CORIF+TOB/COIP+RIF+PORIF+SAMIP+POFEP+SAMCombinations of antibiotics demonstrating enhancedactivity against CRAB*:IP,MP,SAM,TZP,FEP,quinolones,aminoglycosidesFederico P,et al.Antimicrob Agents Chemother.AcceptedCombination therapynVarious combinations of a carbapenem with sulbactam,tobramycin,amikacin,colistin,rifampicin and aztreonam have been assessed,with somewhat mixed results.nClinical experience with combination therapy is limited.Karageorgopoulos DE et al.Lancet Infect Dis.,2008,8:751-762.CRAB的联合治疗 预防措施？预防措施？Hand HygineIsolation of patients(infected or colonized)environment sterilization Decrease clonal spreadMolecular epidemiologic investigationsEnvironmental culturesAntibiotic managementCLINICAL MICROBIOLOGY REVIEWS,July 2008,p.538582Gowns/gloveseye protectionDedicate non-critical devices to patient room病例分析（略）结论多重耐药不动杆菌在增加每家医院有耐药株的克隆传播、相同克隆株传播耐药机制复杂出现多种新机制多药联合治疗关键：院内感染控制 谢谢大家