Bacteria in the respiratory tract—how to treat? Or do not treat?

Background Acute and chronic respiratory tract infections are a common cause of inappropriate antimicrobial prescription. Antimicrobial therapy leads to the development of resistance and the emergence of opportunistic pathogens that substitute the indigenous microbiota. Methods This review explores the major challenges and lines of research to adequately establish the clinical role of bacteria and the indications for antimicrobial treatment, and reviews novel therapeutic approaches. Results In patients with chronic pulmonary diseases and structural disturbances of the bronchial tree or the lung parenchyma, clinical and radiographic signs and symptoms are almost constantly present, including a basal inflammatory response. Bacterial adaptative changes and differential phenotypes are described, depending on the clinical role and niche occupied. The respiratory tract has areas that are potentially inaccessible to antimicrobials. Novel therapeutic approaches include new ways of administering antimicrobials that may allow intracellular delivery or delivery across biofilms, targeting the functions essential for infection, such as regulatory systems, or the virulence factors required to cause host damage and disease. Alternatives to antibiotics and antimicrobial adjuvants are under development. Conclusions Prudent treatment, novel targets, and improved drug delivery systems will contribute to reduce the emergence of antimicrobial resistance in lower respiratory tract infections.