鲍曼不动杆菌的研究进展
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摘要
不动杆菌属(Acinetobacter)是1954年由Brisou等人提出菌属概念,1968年Baumann等人确认Acinetobacter的表型特征,其最重要的代表就是鲍曼不动杆菌(Acinetobacter Baumanii)。在过去的30年中,由于其具有的显著的获得性耐药能力,使其成为威胁当前抗生素的病原微生物之一,也是所有国家的医院内感染的主要原因之一。目前出现对所有已知抗生素有抗性的鲍曼不动杆菌菌株,已引起世界卫生组织的高度重视。该菌通常针对最脆弱的住院患者和严重呼吸道疾病患者。根据回顾性的研究报告,医院获得性肺炎仍是由该病原微生物引起的最常见的感染。最近,涉及中枢神经系统、皮肤和软组织和骨的感染已经出现,这将对医疗机构造成严重威胁。目前有研究认为广谱抗菌药物和免疫抑制剂的广泛应用,可诱导细菌基因发生改变形成多重耐药鲍曼不动杆菌(multidrug-resistant Acinetobacter Baumannii,MDRAB),其耐药机制为产OXA-23型碳青霉烯酶、抗生素作用靶位变异、细菌生物被膜的形成和外排泵基因的影响。面对MDRAB院内快速传播的严峻医疗形势,加强医院感控管理、联合应用抗菌药物和细菌疫苗的研究,为临床上防治MDRAB的产生提供治疗方向。作者主要对近年来鲍曼不动杆菌的耐药机制和应对措施研究作一综述。
Acinetobacter was put forward by Brisou in 1954. Bauman confirmed the phenotypic characteristics of Acinetobacter in 1968. Acinetobacter baumannii is the most important representative of Acinetobacter. In the past 30 years,because of its remarkable acquired resistance,it has become one of the pathogenic microorganisms threatening current antibiotics and one of the main causes of nosocomial infections in all countries. It has been reported that Acinetobacter Baumannii strains resistant to all known antibiotics have attracted great attention of WHO. The bacteria are usually targeted at the most vulnerable inpatients and those with severe respiratory diseases. According to the review report,hospital acquired pneumonia is still the most common infection caused by the pathogenic microorganism. However,in recent years,infections involving the central nervous system,skin and soft tissue and bone have emerged,which will pose a serious threat to medical institutions. At present,it is believed that the wide application of broad-spectrum antibiotics and immunosuppressants can induce gene alteration of bacteria to form multidrug-resistant Acinetobacter Baumannii( MDRAB). Its drug resistance mechanism is OXA-23 carbapenemase production,target mutation of antibiotic action and bacterial biofilm. Formation and efflux pump genes. Facing the severe medical situation of rapid spread of MDRAB in hospital,strengthening the management of nosocomial infection and the study of combined application of antibiotics and bacterial vaccines provide the treatment direction for preventing and curing the occurrence of MDRAB in clinic. In this paper,we reviewed the mechanism of resistance to Acinetobacter Baumannii and the countermeasures in recent years.
Acinetobacter was put forward by Brisou in 1954. Bauman confirmed the phenotypic characteristics of Acinetobacter in 1968. Acinetobacter baumannii is the most important representative of Acinetobacter. In the past 30 years,because of its remarkable acquired resistance,it has become one of the pathogenic microorganisms threatening current antibiotics and one of the main causes of nosocomial infections in all countries. It has been reported that Acinetobacter Baumannii strains resistant to all known antibiotics have attracted great attention of WHO. The bacteria are usually targeted at the most vulnerable inpatients and those with severe respiratory diseases. According to the review report,hospital acquired pneumonia is still the most common infection caused by the pathogenic microorganism. However,in recent years,infections involving the central nervous system,skin and soft tissue and bone have emerged,which will pose a serious threat to medical institutions. At present,it is believed that the wide application of broad-spectrum antibiotics and immunosuppressants can induce gene alteration of bacteria to form multidrug-resistant Acinetobacter Baumannii( MDRAB). Its drug resistance mechanism is OXA-23 carbapenemase production,target mutation of antibiotic action and bacterial biofilm. Formation and efflux pump genes. Facing the severe medical situation of rapid spread of MDRAB in hospital,strengthening the management of nosocomial infection and the study of combined application of antibiotics and bacterial vaccines provide the treatment direction for preventing and curing the occurrence of MDRAB in clinic. In this paper,we reviewed the mechanism of resistance to Acinetobacter Baumannii and the countermeasures in recent years.
引文
[1]胡付品,朱德妹,汪复,等.2014年CHINET中国细菌耐药性监测[J].中国感染与化疗杂志,2015,15(5):401-410.
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[3] Peleg AY,Seifert H,Paterson DL. Acinetobacter baumannii:emergence of a successful pathogen[J].Clin Microbiol Rev,2008,21(3),538-582.
[4] Ghajavand H,Esfahani BN,Havaei SA,et al.Molecular identification of Acinetobacter baumannii isolated from intensive care units and their antimicrobial resistance patterns[J].Adv Biomed Res,2015,4:110.
[5]吴宝刚,万小旭,刘丹,等.重症监护病房老年患者鲍曼不动杆菌感染的临床特点及药敏分析[J].中国医科大学学报,2016,45(5):406-408,413.
[6]李晓红,郭宁辉,杨婧,等.某医院ICU住院患者鲍曼不动杆菌流行特征与耐药性分析[J].中国消毒学杂志,2016,33(4):338-340.
[7]陈娇,胡雪飞,刘康,等.2012-2014年2217株鲍曼不动杆菌感染分布及耐药性监测[J].中国微生态学杂志,2016,28(4):417-419,424.
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[10]张吉生,王英,范学财,等.我院流行鲍曼不动杆菌OXA及Amp C酶基因型分析[J].中华全科医学,2016,14(2):270-272.
[11]陈明慧,霍茜瑜,李雪,等.临床分离碳青霉烯类耐药鲍曼不动杆菌常见耐药基因检测及同源性分析[J].中国卫生检验杂志,2016,26(4):587-589.
[12]温海初,牛雨佳,陈丽华.鲍曼不动杆菌耐药性相关基因及其调控机制研究进展[J].临床检验杂志,2016,34(2):137-139.
[13] Heidary M,Salimi Chirani A,Khoshnood S,et al.Molecular detection of aminoglycoside-modifying enzyme genes in Acinetobacter baumannii clinical isolates[J]. Acta Microbiol Immunol Hung,2017,64(2):143-150.
[14] Kr9ger C,Kary SC,Schauer K,et al.Genetic regulation of virulence and antibiotic resistance in Acinetobacter baumannii[J].Genes(Basel),2017,8(1):12.
[15] Lin MF,Lin YY,Yeh HW,et al.Role of the Bae SR twocomponent system in the regulation of Acinetobacter baumannii ade AB genes and its correlation with tigecycline susceptibility[J].BMC Microbiol,2014,14:119.
[16]陈菁,战榕,李宏,等.多重耐药鲍曼不动杆菌的耐消毒剂状况及qac E△1基因调查[J].中国卫生检验杂志,2015,25(3):431-434.
[17] Liu WL,Liang HW,Lee MF,et al.The impact of inadequate terminal disinfection on an outbreak of imipenemresistant Acinetobacter baumannii in an intensive care unit[J].PLoS One,2014,9(9):e107975.
[18]张银维,周华,蔡洪流,等.鲍曼不动杆菌血流感染临床特征和死亡危险因素分析[J].中华内科杂志,2016,55(2):121-126.
[19]方乐,胡江,陈敬银,等.2013-2015年887株鲍曼不动杆菌的临床感染分布及耐药分析[J].现代预防医学,2016,43(12):2275-2279.
[20]晏奎,温汉春,陈一强.等.磷霉素联合左氧氟沙星对鲍曼不动杆菌生物膜的体外研究[J].中国临床药理学杂志,2015,3l(4):276-278.
[21] Kuo Lee R,Harris G,Yan H,et al.Intranasal immunization protects against Acinetobacter baumannii-associated pneumonia in mice[J].Vaccine,2015,33(1):260-267.
[22] McConnell MJ,Domínguez-Herrera J,Smani Y,et al.Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii[J].Infect Immun,2011,79(1):518-526.
[23] McConnell MJ,Rumbo C,Bou G,et al. Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii[J].Vaccine,2011,29(34):5705-5710.
[24] Luo G,Lin L,Ibrahim AS,et al.Active and passive immunization protects against lethal,extreme drug resistantAcinetobacter baumannii infection[J]. PLoS One,2012,7(1):e29446.
[25]蔡昌芝,冯强,杨赟,等.鲍曼不动杆菌外膜蛋白Al S-1969的克隆表达及免疫保护机制初步研究[J].免疫学杂志,2016,32(2):104-108.
[26]邹全明,石云.超级细菌疫苗研究进展[J].第三军医大学学报,2016,38(7):663-668.
[2] Custovic A,Smajlovic J,Tihic N,et al. Epidemiological monitoring of nosocomial infections caused by Acinetobacter baumannii[J].Med Arch,2014,68(6):402-406.
[3] Peleg AY,Seifert H,Paterson DL. Acinetobacter baumannii:emergence of a successful pathogen[J].Clin Microbiol Rev,2008,21(3),538-582.
[4] Ghajavand H,Esfahani BN,Havaei SA,et al.Molecular identification of Acinetobacter baumannii isolated from intensive care units and their antimicrobial resistance patterns[J].Adv Biomed Res,2015,4:110.
[5]吴宝刚,万小旭,刘丹,等.重症监护病房老年患者鲍曼不动杆菌感染的临床特点及药敏分析[J].中国医科大学学报,2016,45(5):406-408,413.
[6]李晓红,郭宁辉,杨婧,等.某医院ICU住院患者鲍曼不动杆菌流行特征与耐药性分析[J].中国消毒学杂志,2016,33(4):338-340.
[7]陈娇,胡雪飞,刘康,等.2012-2014年2217株鲍曼不动杆菌感染分布及耐药性监测[J].中国微生态学杂志,2016,28(4):417-419,424.
[8] Lzureanu V,Poro爧nicu M,Gndac C,et al.Infection with Acinetobacter baumannii in an intensive care unit in the Western part of Romania[J]. BMC Infect Dis,2016,16(1):95.
[9]孙静娜,王国欣,刘泽世,等.鲍曼不动杆菌临床分离株的耐药性分析[J].现代预防医学,2015,42(6):1149-1151.
[10]张吉生,王英,范学财,等.我院流行鲍曼不动杆菌OXA及Amp C酶基因型分析[J].中华全科医学,2016,14(2):270-272.
[11]陈明慧,霍茜瑜,李雪,等.临床分离碳青霉烯类耐药鲍曼不动杆菌常见耐药基因检测及同源性分析[J].中国卫生检验杂志,2016,26(4):587-589.
[12]温海初,牛雨佳,陈丽华.鲍曼不动杆菌耐药性相关基因及其调控机制研究进展[J].临床检验杂志,2016,34(2):137-139.
[13] Heidary M,Salimi Chirani A,Khoshnood S,et al.Molecular detection of aminoglycoside-modifying enzyme genes in Acinetobacter baumannii clinical isolates[J]. Acta Microbiol Immunol Hung,2017,64(2):143-150.
[14] Kr9ger C,Kary SC,Schauer K,et al.Genetic regulation of virulence and antibiotic resistance in Acinetobacter baumannii[J].Genes(Basel),2017,8(1):12.
[15] Lin MF,Lin YY,Yeh HW,et al.Role of the Bae SR twocomponent system in the regulation of Acinetobacter baumannii ade AB genes and its correlation with tigecycline susceptibility[J].BMC Microbiol,2014,14:119.
[16]陈菁,战榕,李宏,等.多重耐药鲍曼不动杆菌的耐消毒剂状况及qac E△1基因调查[J].中国卫生检验杂志,2015,25(3):431-434.
[17] Liu WL,Liang HW,Lee MF,et al.The impact of inadequate terminal disinfection on an outbreak of imipenemresistant Acinetobacter baumannii in an intensive care unit[J].PLoS One,2014,9(9):e107975.
[18]张银维,周华,蔡洪流,等.鲍曼不动杆菌血流感染临床特征和死亡危险因素分析[J].中华内科杂志,2016,55(2):121-126.
[19]方乐,胡江,陈敬银,等.2013-2015年887株鲍曼不动杆菌的临床感染分布及耐药分析[J].现代预防医学,2016,43(12):2275-2279.
[20]晏奎,温汉春,陈一强.等.磷霉素联合左氧氟沙星对鲍曼不动杆菌生物膜的体外研究[J].中国临床药理学杂志,2015,3l(4):276-278.
[21] Kuo Lee R,Harris G,Yan H,et al.Intranasal immunization protects against Acinetobacter baumannii-associated pneumonia in mice[J].Vaccine,2015,33(1):260-267.
[22] McConnell MJ,Domínguez-Herrera J,Smani Y,et al.Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii[J].Infect Immun,2011,79(1):518-526.
[23] McConnell MJ,Rumbo C,Bou G,et al. Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii[J].Vaccine,2011,29(34):5705-5710.
[24] Luo G,Lin L,Ibrahim AS,et al.Active and passive immunization protects against lethal,extreme drug resistantAcinetobacter baumannii infection[J]. PLoS One,2012,7(1):e29446.
[25]蔡昌芝,冯强,杨赟,等.鲍曼不动杆菌外膜蛋白Al S-1969的克隆表达及免疫保护机制初步研究[J].免疫学杂志,2016,32(2):104-108.
[26]邹全明,石云.超级细菌疫苗研究进展[J].第三军医大学学报,2016,38(7):663-668.