Tenover Fred C
Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Am J Med. 2006 Jun;119(6 Suppl 1):S3-10; discussion S62-70. doi: 10.1016/j.amjmed.2006.03.011.
The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.
细菌对抗菌药物产生耐药性的能力使得细菌感染的治疗日益复杂。抗菌药物通常根据其主要作用机制进行分类。作用机制包括干扰细胞壁合成（如β-内酰胺类和糖肽类药物）、抑制蛋白质合成（大环内酯类和四环素类）、干扰核酸合成（氟喹诺酮类和利福平）、抑制代谢途径（甲氧苄啶-磺胺甲恶唑）以及破坏细菌膜结构（多粘菌素类和达托霉素）。细菌可能对≥1类抗菌药物具有固有耐药性，或者可能通过新发突变或从其他生物体获得耐药基因而获得耐药性。获得的耐药基因可能使细菌产生破坏抗菌药物的酶、表达阻止药物到达其细胞内靶点的外排系统、改变药物的靶点部位，或者产生绕过药物作用的替代代谢途径。抗菌药物敏感细菌从耐药菌株获得新的遗传物质可能通过接合、转化或转导发生，转座子通常促进多重耐药基因整合到宿主基因组或质粒中。使用抗菌药物为耐药菌株的出现创造了选择压力。本文回顾了3个病例史——一个涉及大肠杆菌对第三代头孢菌素的耐药性，另一个关注耐万古霉素金黄色葡萄球菌的出现，第三个详细介绍铜绿假单胞菌的多重耐药性——以说明耐药细菌产生的多种方式。
