课件：铜绿假单胞菌感染的流行趋势及治疗进展.ppt

多重耐药铜绿假单胞菌的流行现状及治疗,2019,-,1,主要内容,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,4,3,2019,-,2,Pseudomonas Aeruginosa(PA),1、生物学性状： 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。 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。 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。 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。,2019,-,3,2、致病性,2019,-,4,定义,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。 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、碳氢酶烯系类、四环素类、氟奎诺酮及磺胺类等耐药。,2019,-,5,铜绿假单胞菌3 年耐药监测结果分析,年华.华中医学杂志,2002,26(4):229-230.,耐药现状,2019,-,6,2007 年中国 C H IN E T 铜绿假单胞菌耐药性监测,2019,-,7,Mohnarin 2008 年度全国细菌耐药监测,2019,-,8,2009 年中国 C H IN E T 细菌耐药性监测,2019,-,9,2009 年中国 C H IN E T 细菌耐药性监测,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胞菌、不动杆菌属和嗜麦芽窄食单胞菌。,2019,-,10,Antimicrobial Resistance Among Clinical Isolates From The Chinese Meropenem Surveillance Study (CMSS), 20032008（美罗培南敏感性监测 (CMSS)报告）,Hui Wang .International Journal of Antimicrobial Agents 35 (2010) 227234,FEP:头孢吡肟 CAZ :头孢他定 TZP:哌拉西林/他唑巴坦,2019,-,11,革兰阴性杆菌耐药状况研究 2008中国美罗培南敏感性监测 (CMSS)报告,王辉.Chinese Journal of Practical Internal Medicine 2010 ,30（ 1）,2019,-,12,中国重症监护病房细菌耐药性监测研究,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 ),2019,-,13,中国重症监护病房革兰阴性菌耐药性连续 7 年监测研究,陈民均.中华医学杂志,2003 ,83 (5 ),2019,-,14,王辉，中华医学杂志，83（5）：385-390.,19942001 年中国重症监护病房非发酵糖细菌的耐药变迁,2019,-,15,ICU环境及护理人员与发生VAP的关系,J Infect Dev Ctries 2010; 4(5):282-291.,2019,-,16,National surveillance of antimicrobial resistance in pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002.,2019,-,17,Emergence o f e x t e n s i v e ly d r u g - r e s i s ta n t a n d pa n d r u g r e s i s ta n t g r a m - n e g at i v e b a c i l l i i n E u r o p e,EUROSURVEILLANCE. 2008,13(47)20,2019,-,18,感染PA的危险因素,CAP,HAP,COPD,MDR-PA,最近住院史;抗菌药物频繁治疗史(过去1年中使用过4个疗程的抗菌药物);严重COPD恶化(级COPD); 以前急性加重期分离到铜绿假单胞菌,或稳定期有铜绿假单胞菌定植,2019,-,19,MDR-PA的耐药机制,主动外排机制：铜绿假单胞菌细胞外膜上有主动外排系统，该系统可将细菌体内的药物排出，致使药物浓度不足以发挥抗菌作用。 渗透障碍：抗菌药物进入细菌体内主要靠渗透作用，细菌外膜有亲水性的外膜孔蛋白(Outer membrane protein，Omp)协助药物渗透入细菌体内，一旦Omp 缺失，则导致耐药产生。铜绿假单胞菌 Omp 的 OprO2 缺失是亚胺培南耐药的主 要 机 制 。 细 菌 生 物 被 膜 (Bacterial biologicalfacing，BBF)：铜绿假单胞菌是产生 BBF 的主要常见细菌。 灭活酶与钝化酶：铜绿假单胞菌通过染色体或质粒介导可产生-内酰胺酶、氨基糖苷钝化酶及 DNA 旋转酶等，致相应抗菌药物耐药。第三代头孢菌素的不适当应用具有强烈诱导和筛选超广谱-内酰胺酶(ESBLs)的作用，导致第三代头孢菌素的耐药。,2019,-,20,治疗疗程,1999-医院获得性肺炎诊断和治疗指南(草案),流感嗜血杆菌 1014 天 ,肠杆菌科 细菌、不动杆菌 1421 天 ,铜绿假单胞菌 2128 天 , 中华结核和呼吸杂志 1999 ，4 ：22 （4 ）,2005-美 国医 院获得性肺炎治疗指南 ,在 应 用 -内酞胺类抗生 素治疗铜绿 假单胞 菌肺 炎 时 , 可 短 期（5D) 联 合氨基 昔类抗生素治疗。 肺炎的治疗疗程，8D与14D疗效相似，但当病原菌为铜绿假单胞菌或不动杆菌属菌 则短 程 治疗 的复燃 率较 高。,2019,-,21,Predictors Of 30 Day Mortality Among Patients With Pseudomonas Aeruginosa Bloodstream Infections: Impact Of Delayed Appropriate Antibiotic Selection,Lodise TP J r, et al.Antimicrob Agents Chemother, 2007, 51: 3510-3515.,对于PA菌血症的治疗，若初始经验治疗不合适延迟52小时，将使病人30天死亡风险明显升高。,治疗时机,2019,-,22,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 ),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,2019,-,23,新药介绍,2019,-,24,针对MDR-PA的联合治疗方案,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,OR,OR,OR,2019,-,25,针对MDR-PA的联合治疗方案,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,2019,-,26,Microbiological activity and clinical efficacy of a colistin and 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 microbiological 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感染有效。,2019,-,27,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 susceptibility 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 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 antimicrobial 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。,2019,-,28,Fosfomycin for the treatment of infections caused by multidrug-resistant 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 brosis) received fosfomycin (25/33 in combination withother antibiotics); 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 Journal of Antimicrobial Agents 34 (2009) 111120,2019,-,29,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 regimens, 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.,2019,-,30,目前PA感染治疗中仍存在的一些问题,1、剂量不