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鲍曼不动杆菌抗生素多重耐药性:耐药机制与感染治疗对策

Multidrug resistance in Acinetobacter baumanni:Mechanisms and anti-infective therapy

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【作者】 凌保东

【Author】 Ling Bao-dong (Institute of Materia Medica and Department of Pharmacology,North Sichuan Medical College,Nanchong 637007)

【机构】 川北医学院药物研究所和药理学教研室

【摘要】 多重以及泛耐药鲍曼不动杆菌导致的感染流行已成为全球关注的公共卫生问题。大多数细菌耐药基因与表型特征均充分反映在耐药鲍曼不动杆菌。鲍曼不动杆菌的外膜通透屏障与药物主动外排泵的协同作用使其呈现明显的天然多重耐药性,而其染色体可整合获取外源性由转座子/整合子可移动基因元件与多重耐药基因相联系的耐药岛区域或携带含有类似的整合子与多重耐药基因盒的质粒,这些基因结构导致该菌进化形成了对多类化学结构各异的临床常用抗生素的高度获得性耐药性,使其感染治疗的药物选择极其有限。尽管可考虑选用碳青霉烯类、含舒巴坦复合制剂、多黏菌素E或联合使用抗生素等治疗鲍曼不动杆菌感染,严重存在的多重耐药性等要求用药时更密切地观察药物的疗效,并参考药物敏感试验结果调整用药方案。虽然新的抗生素如替加环素等显示一定的体外抗鲍曼不动杆菌活性,但其临床疗效仍待继续研究。采取各种风险管理措施有效控制医院性细菌感染疾病包括合理使用各类抗生素是防止及减少鲍曼不动杆菌感染以及耐药性发生和传播的重要对策。

【Abstract】 Infections associated with Acinetobacter baumanni has been increasingly observed around the globe with the rapid emergence and high prevalence of multidrug resistance or pan-resistance in this bacterial species. A.baumanii itself displays significant intrinsic resistance owning to the interplay between the outer membrane permeability barrier and active drug efflux pumps.Most mechanisms of resistance occurred in bacteria have been identified in A.baumannni with the predominant observations either in the chromosome or on plasmids of the clusters of multidrug resistance genes and mobile genetic elements such as tranposons and integrons,which are responsible for the unusual high-levels of acquired multidrug resistance and also result in the very limited drug options for the anti-infective therapy.Although carbapenems,sulbactam-containing antibiotic combinations,colistin or other antibiotic combination therapy may be selected for therapy of A.baumanni infections,the clinical efficacy of these drug regimens remains to be observed closely and if needed,the drug selection should be adjusted by taking into account of the antibiotic susceptibility testing.Despite some newer antibiotics including tigecycline display anti-Acinetobacter activity in vitro,their clinical efficacy remains to be further studied.Effective risk management for nosocomial infection control including the prudent use of antibiotics is a key in preventing or reducing the infections by A.baumanni as well as their emergence and persistence of drug resistance.

【关键词】 鲍曼不动杆菌; 多重耐药性; 泛耐药性; 耐药机制; 感染治疗;

【Key words】 Acinetobacter baumanni; Multidrug resistance; Pan-drug resistance; Resistance mechanisms; Antiinfective therapy;

【分类号】R962;R378.993;R978.1;

【基金】 国家自然科学基金(项目编号30973662);四川省重点科技项目(编号:2006J13-030及07ZA034)

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