Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada.
Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada.
Chest. 2018 Nov;154(5):1202-1212. doi: 10.1016/j.chest.2018.06.019. Epub 2018 Jun 28.
Since their introduction into health care and clinical practice in the early 20th century, antibiotics have revolutionized medicine. Alarmingly, these drugs are increasingly threatened by bacteria that have developed a broad diversity of resistance mechanisms. Antibiotic resistance can be transferred between bacteria, often on mobile genetic elements; be acquired from the environment; or arise through mutation because of selective pressures of the drugs themselves. There are various strategies to resistance, including active efflux of the drug from the bacterial cell, reduced permeability of the cell envelope, alteration of the drug's target within the bacterial cell, and modification or destruction of the antibiotic. Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis frequently are implicated in respiratory infections, often manifesting with reduced susceptibility to multiple classes of antibiotics. Some mechanisms of resistance, such as the β-lactamases that confer resistance to penicillins and related drugs, have been well characterized and are widespread in clinical isolates. Other newly identified determinants, including the colistin resistance gene mcr-1, are spreading rapidly worldwide and threaten last-resort treatments of multidrug-resistant organisms. Various approaches to detecting antibiotic resistance provide surveys of the determinants that are available for transfer into pathogenic bacteria. Together with molecular characterization of newly identified mechanisms, this surveillance can target drug discovery efforts and increase antibiotic stewardship. A greater understanding of the mechanisms of antibiotic resistance in respiratory pathogens combined with rapid diagnostics ultimately will reduce treatment failure due to inappropriate antibiotic use and prevent further spread of resistance.
自 20 世纪初引入医疗保健和临床实践以来，抗生素彻底改变了医学。令人震惊的是，这些药物正日益受到具有广泛耐药机制的细菌的威胁。抗生素耐药性可以在细菌之间转移，通常是通过移动遗传元件；可以从环境中获得；也可以由于药物本身的选择压力而通过突变产生。细菌有各种耐药策略，包括将药物从细菌细胞中主动排出、减少细胞包膜的通透性、改变细菌细胞内药物的靶标，以及修饰或破坏抗生素。肺炎链球菌、流感嗜血杆菌、铜绿假单胞菌和结核分枝杆菌经常与呼吸道感染有关，通常表现出对多种类别的抗生素的敏感性降低。一些耐药机制，如赋予青霉素和相关药物耐药性的β-内酰胺酶，已经得到了很好的描述，并在临床分离株中广泛存在。其他新发现的决定因素，包括多粘菌素耐药基因 mcr-1，正在全球迅速传播，威胁着多药耐药生物的最后治疗手段。各种检测抗生素耐药性的方法提供了可转移到致病性细菌的决定因素的调查。结合新发现的机制的分子特征，这种监测可以针对药物发现工作，并增加抗生素管理。对呼吸道病原体中抗生素耐药机制的更好理解，加上快速诊断，最终将减少因不合理使用抗生素而导致的治疗失败，并防止耐药性进一步传播。
