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1、不动杆菌流行及治疗,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ICU院内获得性肺炎病原菌的比例及对常用抗菌药物的耐药率,Clin Infect Dis 2005: 41: 848-854,2008年CHINET耐药监测革兰阴性菌菌种分布,Multidrug-resistan
2、t A. baumannii (MDRAB),Resistance to 3 or more than 3 kinds of antibiotics antipseudomonal cephalosporins antipseudomonal carbapenems -lactamase inhibitor combinations antipseudomonal fluoroquinolones aminoglycosides Pandrug-resistant A. baumannii, PDRAB resistance to all antibiotics but polymycin a
3、nd tigecycline,“XDR”： extreme drug resistance,对抗绿脓的头孢菌素 抗绿脓的碳青霉烯类 -内酰胺抗生素复合制剂 氟喹诺酮类 氨基糖苷类 替加环素 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,20-30环境下生长良
4、好，抵抗力强，在干燥的物体表面鲍曼不动杆菌可存活25天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,Perez F, et al. Antimicrob Agents Chemother 2007; 51: 3471-84.,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；
5、 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-transmission,X represents multi-drugs
6、 resistant pathogens culture positive sites,无处不在！,Acinetobacter Transmission in the Hospital Setting,Direct or indirect contact Contaminated hands of healthcare workers Airborne transmission via aerosol production (e.g., hydrotherapy) may occur,Environmental Contamination with Acinetobacter,Bed rail
7、s Bedside tables Ventilators Infusion pumps Mattresses Pillows Air humidifers Patient monitors,X-ray view boxes Curtain rails Curtains Equipment carts Sinks Ventilator circuits Floor mops,抗生素的应用 ？！,Susceptiblity of A. baumannii: 1994-2004 (1874 isolates),Susceptibiligy(%),Year,Antimicrobial Resistan
8、ce among Acinetobacter sp., From ICUs 1986-2003,2008年12家医院3508株不动杆菌属(鲍曼不动86.2%) 细菌的耐药率（%）,Major infections due to Acinetobacter,Ventilator-associated pneumonia Urinary tract Bloodstream infection infection Secondary meningitis Skin/wound infections Endocarditisperitonitis Endophthalmitis,How to trea
9、t infections caused by MDR A. baumannii,Sulbactam combinations Colistin tigecycline,FASS 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 infections,Levin et al. Int J Antimicrob Agents 2003
10、;21:58-62,CRAB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-多黏菌素,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037%. 雾化吸入有助
11、于减少全身用药的副作用,并在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.,Clin Microbiol Rev 2008: 21: 538-582.,High resistance to colistin of MDRAB from Korea,Considering the increasing use of colistin, independent but frequent emergence of colistin resistance in MDRAB is of great concern.,Kwan Soo Ko, JAC 2007,60:1163-7 Young
12、Kyoung Parka, DMID 2009, 64:43-51,BIG BUG!,Colistin,Good outcome to MDR AB infection，including: bacteremia、pneumonia、urinary tract infection、wound infection、 meningitis,Only 10.8 CRAB were resistant to colistin in China Mainland,Tigecycline: the saviour?,22 microbiological studies reporting data for
13、 2384 Acinetobacter spp, 90% isolates (including MDR and CRAB) were susceptible 42 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
14、:44-45,Tetracycline Susceptibility Testing in Isolates of Acinetobacte from a U.S. Military Hospital,Kevin S. Akers, AAC, 2009, accepted,Susceptibility of 73 IPM-I or R A. baumannii isolates to tigecycline,S:6 isolates（8.2），I: 6 isolates（8.2），R:61 isolates（83.6）,Susceptibility of 43 IPM-S A. baumann
15、ii isolates to tigecycline,S:19 isolates（44.2），I:6 isolates（14.0），R:18 isolates（41.9）,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,Combinations of antibiotics demonstrating enhanced activity against CRAB,*: IP, MP, SAM, TZP, FEP, quinolones, aminoglycosides,Federico P, et al. Antimicrob Agents Chemother. Accepted
16、,Combination therapy,Various combinations of a carbapenem with sulbactam, tobramycin, amikacin, colistin, rifampicin and aztreonam have been assessed, with somewhat mixed results. Clinical 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？,Hand Hygine Isolation of patients (infected or colonized) environment sterilization,Decrease clonal spread,Molecular epidemiologic investigations Environmental cultures Antibiotic management,
