Antimicrobial Resistance and Respiratory Infections

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.