University of Manchester, Manchester, UK.
Curr Pharm Des. 2013;19(2):223-38.
Acinetobacter spp. are Gram-negative bacteria that have become one of the most difficult pathogens to treat. The species A. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. It is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating Gram-negative bacteria, including the fluoroquinolones and the cephalosporins. Some members of the species have accumulated these resistance genes in large resistance islands, located in a "hot-spot" within the bacterial chromosome. The only conventional remaining treatment options were the carbapenems. However, A. baumannii possesses an inherent class D β-lactamase gene (blaOXA-51-like) that can have the ability to confer carbapenem resistance. Additionally, mechanisms of carbapenem resistance have emerged that derive from the importation of the distantly related class D β-lactamase genes blaOXA-23 and blaOXA-58. Although not inducible, the expression of these genes is controlled by mobile promoters carried on ISAba elements. It has also been found that other resistance genes including the chromosomal class C β-lactamase genes conferring cephalosporin resistance are controlled in the same manner. Colistin is now considered to be the final drug capable of treating infections caused by carbapenem-resistant A. baumannii; however, strains are now being isolated that are resistant to this antibiotic as well. The increasing inability to treat infections caused by A. baumannii ensures that this pathogen more than ranks with MRSA or Clostridium difficile as a threat to modern medicine.
鲍曼不动杆菌属是革兰氏阴性细菌，已成为最难治疗的病原体之一。30 年前鲜为人知的物种 A. 鲍曼不动杆菌由于能够引起免疫功能低下患者的感染而变得尤为突出。现在，它已成为许多医院的主要病原体，因为它已经获得了几乎所有能够治疗革兰氏阴性细菌的抗生素的耐药基因，包括氟喹诺酮类和头孢菌素类。该物种的一些成员在细菌染色体的“热点”内的大型耐药岛上积累了这些耐药基因。唯一剩下的常规治疗选择是碳青霉烯类。然而，鲍曼不动杆菌具有内在的 D 类β-内酰胺酶基因（blaOXA-51 样），可赋予碳青霉烯类耐药性。此外，还出现了源自远缘 D 类β-内酰胺酶基因 blaOXA-23 和 blaOXA-58 的碳青霉烯类耐药机制。尽管这些基因不可诱导，但它们的表达受 ISAba 元件上携带的可移动启动子控制。还发现，包括赋予头孢菌素耐药性的染色体 C 类β-内酰胺酶基因在内的其他耐药基因也以同样的方式受到控制。多粘菌素现在被认为是治疗碳青霉烯类耐药鲍曼不动杆菌感染的最后一种药物；然而，现在已经分离出对这种抗生素耐药的菌株。越来越无法治疗由鲍曼不动杆菌引起的感染，这确保了这种病原体与耐甲氧西林金黄色葡萄球菌或艰难梭菌一样，是对现代医学的威胁。
