Inhaled combined antibacterials against biofilm-forming antibiotic-resistant bacteria for the management of pulmonary bacterial infections

Pulmonary antibiotic delivery is a mainstay of treatment for severe pulmonary infections associated with cystic fibrosis, chronic obstructive pulmonary disease and non-CF bronchiectasis. However, abnormal or hypersecreted mucus, antibiotic resistance, and bacterial biofilms hinder the efficacy of conventional pulmonary drug delivery modalities in treating lung infections. Many different therapeutic drug delivery strategies have been developed to overcome these barriers and improve the performance of inhaled antibiotics against multi-drug resistant and biofilm-associated bacterial infections, including inhaled combined antibacterial agents. Apart from conventional or novel antibiotics, combination therapies may include adjunct agents with antibacterial activity, such as biofilm eradicating agents, biofilm dispersal agents, biofilm preventers, mucoactive agents, and quorum sensing inhibitors. Optimized synergistic formulations of combined antibacterials and effective inhalable delivery strategies are essential in the development of novel treatments for biofilm-forming and antibacterial-resistant respiratory infections. This review discusses the benefits and rationale for developing combined inhaled antibacterials for the effective management of lung infections.