Purpose: The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm.
Method: Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy.
Results: Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone.
Conclusions: The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.
Keywords: biofilm; ciprofloxacin; inhalation; mannitol; respiratory tract infection.