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1、1铜绿假单胞菌在临床上耐药现状2多药耐药铜绿假单胞菌的耐药机制铜绿假单胞菌感染的治疗现状生物学特性及致病性431、生物学性状：生物学性状：u假单胞菌属，是最常见的非发酵革兰阴性菌之一，菌体细长且长短不一，铜绿假单胞菌有时呈球杆状或线状，成对或短链状排列。带菌毛。u专性需氧菌，抵抗力强，最适生长温度为35，在4 不生长而在42度生长是它的一个特点。u可产生带荧光的水溶性色素，故在血平板上会有透明溶血环。 u本菌为条件致病菌，是医院内感染的重要致病菌之一。可引起皮肤、呼吸道、泌尿系、烧伤感染等。致病物质致病物质生物学活性生物学活性菌毛对宿主细胞具有粘附作用荚膜多糖抗吞噬作用毒素毒素内毒素致发热，休
2、克，DIC等外毒素A抑制蛋白质合成细胞溶解毒素有杀白细胞素等，能损伤细胞和组织蛋白分解酶分解蛋白质，损伤多种细胞和组织胞外酶S人类肺部感染的重要因子弹性蛋白酶损伤血管，抑制中性粒细胞功能碱性蛋白酶损伤组织，抗补体，灭活IgG，抑制中性粒细胞功能磷酸酯酶C组织损伤p多重耐药菌(multiple resistant bacteria MDR)是指有多重耐药性的病原菌。其定义为一种微生物对三类（比如氨基糖苷类、红霉素、内酰胺类）或三类以上抗菌药物同时耐药。p泛耐药菌株（pan-drug resistance, PDR)指除多粘菌素类外，对几乎所有测试抗菌素耐药。比如对氨基糖苷、青霉素、头孢菌素、碳氢
3、酶烯系类、四环素类、氟奎诺酮及磺胺类等耐药。年华.华中医学杂志,2002,26(4):229-230.耐药现状2009 年共收集临床分离株43670 株 ,其中革兰阳性菌 12668 株 ,占 29 % ,革兰阴性菌 31002株 ,占 71 %。肠杆菌科细菌中最多见者依次为大肠埃希菌、克雷伯菌属、肠杆菌属和变形杆菌属;非发酵糖菌中最多见者依次为铜绿假单非发酵糖菌中最多见者依次为铜绿假单非发酵糖菌中最多见者依次为铜绿假单非发酵糖菌中最多见者依次为铜绿假单胞菌、不动杆菌属和胞菌、不动杆菌属和胞菌、不动杆菌属和胞菌、不动杆菌属和嗜麦芽窄食单胞菌。嗜麦芽窄食单胞菌。嗜麦芽窄食单胞菌。嗜麦芽窄食单胞菌
4、。Hui Wang .International Journal of Antimicrobial Agents 35 (2010) 227234FEP:头孢吡肟 CAZ :头孢他定 TZP:哌拉西林/他唑巴坦王辉.Chinese Journal of Practical Internal Medicine2010 ,30（ 1）在 ICU ,院内感染的比例明显高于非 ICU ,并且ICU 的主要致病菌中 ,铜绿假单胞菌、鲍曼不动杆菌和金黄色葡萄球菌的耐药率明显高于非 ICU。中华检验医学杂志,2004 ,11 27 (11 )陈民均.中华医学杂志,2003 ,83 (5 )王辉，中华医学杂志
5、，83（5）：385-390.19942001 年中国重症监护病房非发酵糖细菌的年中国重症监护病房非发酵糖细菌的耐药变迁耐药变迁J Infect Dev Ctries 2010; 4(5):282-291.EUROSURVEILLANCE. 2008,13(47)20结构性肺病，应用糖皮质激素，过去1月内应用广谱抗菌药，中性粒细胞52小时，将使病人30天死亡风险明显升高。治疗时机传统治疗药物新研发的抗假单胞菌药物多利培南 (Doripenem)西他沙星（sitafloxacin）比阿培南（Biapenem )铜绿假单胞菌对以下药物具有天然耐药性铜绿假单胞菌对以下药物具有天然耐药性:氨苄西林、阿
6、莫西林、阿莫西林/克拉维酸、第一、二代头孢菌素、头孢噻肟、头孢曲松、萘啶酸和甲氧嘧啶等。哌拉西林，替卡西林头孢他定，头孢哌酮哌拉西林/他唑巴坦替卡西林/克拉维酸头孢哌酮舒巴坦环丙沙星，左氧氟沙星多粘菌素类（多粘菌素B,E）药物治疗方案药物药物 西他沙星西他沙星多利培南多利培南比阿培南比阿培南抗菌活性抗G+菌（包括肺炎链球菌、MRSA）活性比氧氟沙星和环丙沙星强16倍和64倍；抗G-菌（包括流感嗜血杆菌，肺炎克雷伯菌，变形杆菌，肠杆菌科细菌，假单胞菌，不动杆菌）活性都比环丙沙星与氧氟沙星强；抗厌氧菌活性是现有喹诺酮中最强者.抗铜绿假单胞菌活性是现有碳青霉烯中最强者。抗G+较美洛培南强，抗G-较亚
7、胺培南强，抗革兰氏阴性菌，特别是抗绿脓杆菌的活性比亚胺培南强；对需氧性革兰阳性菌的抗菌活性稍低于亚胺培南；抗厌氧菌的活性与亚胺培南相同。不良反应胃肠功能紊乱17.2%（主要为腹泻）发生率4.4%，主要为腹泻（0.7%）与皮疹（0.6%）等皮疹/皮肤瘙痒、恶心、呕吐以及腹泻等。新药介绍抗假单胞头孢菌素抗假单胞喹诺酮类抗假单胞菌碳青霉烯类-内酰胺类/-内酰胺酶抑制剂氨基糖苷类OROROROROROR多粘菌素头孢他定头孢哌酮舒巴坦磷霉素多粘菌素利福平多粘菌素妥布霉素多利培南Microbiological activity and clinical efficacy of a colistin and
8、 rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections.Tascini C, The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiol
9、ogical and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.J Chemother. 2004 Jun;16(3):282-7.联合治疗粘菌素+利福平的联合治疗方案可能对MDR-PA
10、感染有效。Antimicrobial therapy and control of multidrug-resistant Pseudomonas aeruginosa bacteremia in a teaching hospital in Taiwan.Leung CH, METHODS: MDR P. aeruginosa isolates were collected at the MacKay Memorial Hospital, Taipei, Taiwan, and antibiotic synergy was investigated based on antibiotic s
11、usceptibility tests using a combination of antibiotics. Isolates of patients with MDR P. aeruginosa bacteremia were selected for genetic analysis by pulsed-field gel electrophoresis.RESULTS: A combination of ceftazidime, amikacin, and sulbactam had significant synergistic effects against bloodstream
12、 MDR P. aeruginosa isolates and was more beneficial clinically compared with other antibiotic combinations. The major source of MDR P. aeruginosa infection was located and stringent infection control measures were enforced.CONCLUSION: The results of this study suggest that use of triple antimicrobia
13、l therapy (ceftazidime, amikacin, and sulbactam) can be a useful alternative treatment for MDR P. aeruginosa infection in certain circumstances. DiviJ Microbiol Immunol Infect. 2008 Dec;41(6):491-8.3药联合治疗头孢他啶+阿米卡星+舒巴坦治疗MDR-PA 感染是不错的选择。 Fosfomycin for the treatment of infections caused by multidrug-r
14、esistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies. In six clinical studies, 33 patients with MDR P. aeruginosa infec-tions (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination withother antibiot
15、ics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potentialutility of this agent.联合治疗磷霉素联合其他抗菌药物可以作为治疗MDR-PA感染的备用选择方案Matthew E. Falagas. International Jour
16、nal of Antimicrobial Agents 34 (2009) 111120 Current treatment of pseudomonal infections in the elderly. In the elderly, in addition to making dose modifications that are needed because of loss of renal function, the prescriber should be more cautious about the use of aminoglycoside-containing regim
17、ens, possibly replacing them with a combination of quinolone and a beta-lactam,notwithstanding the possible increased pressure for selection of resistance with the latter combination.老年肺炎的治疗老年人因肾功能减退的原因，PA肺炎应慎用氨基糖苷类药物，尽量联合喹诺酮类药物或内酰胺类药物。Pappas G, Drugs Aging. 2009;26(5):363-79.1、剂量不足：氨基糖苷类药物及喹诺酮类药物2、
18、时机延后：.3、生物被膜： 治疗中对于细菌生物被膜重视不够:铜绿假单胞菌较易形成生物被膜 。目前临床上对于易于产生生物被膜的肺部铜绿假单胞菌感染 ,如呼吸机相关性肺炎 ,临床工作者较少使用抑制生物被膜形成的药物如大环内酯类药物。4、过度治疗：无法很好区分PA的定植定植还是感染感染。 目前尚缺乏有效杀灭目前尚缺乏有效杀灭 MDR-PA 并控制其播散的方法。依据临床特点并控制其播散的方法。依据临床特点及其耐药机制及其耐药机制 ,MDR-PA 的预防与治疗需要采用综合措施的预防与治疗需要采用综合措施。MDR -PA的预防策略消除感染危险因素：要尽量避免或减少入住 ICU、机械通气、使用多种抗生素等危险因素。 由于经手传播可造成 ICU内同一克隆 MDR-PA菌株感染的流行 ,因此强调防止致病菌经污染的医务人员手、鼻饲液、导尿管及水浴加温等途径传播与扩散。 主动监测并隔离 MDR-PA感染的患者 ,实施环境卫生及隔离等综合预防措施可有效地控制克隆菌株扩散。 尽早拔除各类导管如导尿管、深静脉置管和气管插管等可减少PA侵入机会。强调对菌株分型及按不同类型进行严格隔离 ,切断传播途径 ,以防止发生多重耐药菌株交叉感染。Thank You !
