114 Investigating the activity of antibiotics at aerosolized concentrations against Burkholderia cepacia complex biofilms

Objectives Burkholderia cepacia complex (Bcc) causes chronic pulmonary infections in patients with Cystic Fibrosis (CF). Bcc isolates are drug resistant and grow as biofilms in vivo , thus protecting themselves from host defences. Currently, there is no effective antimicrobial therapy for CF patients infected with Bcc. New aerosolized antimicrobials can deliver very high intrapulmonary concentrations of drug that may be able to overcome this antimicrobial resistance. The objective of this study was to compare the activity of tobramycin at systemically achievable vs aerosolized concentrations on Bcc biofilms cultured under continuous flow in the novel microfluidic Bioflux system. Methods Biofilms of CF Burkholderia multivorans (tagged with gfp) were generated for 24 hours and were treated with 8 and 1,000 mg/ml tobramycin for 24 hrs. Results Analysis of each channel demonstrated that biofilm biomass decreased in comparison to the controls after treatment with tobramycin. However, while biomass was decreased, confocal Z-stack images indicated that thickness of microcolonies within treated biofilms (8 mg/ml, 33 mm; 1000 mg/ml, 41 mm) are similar to controls (48 hr, 40 mm). Conclusion In conclusion, although tobramycin at concentrations achievable by aerosolization does not eradicate Bcc biofilms in vitro , additional work is underway to determine its effect on the viability of bacterial cells within this biofilm. Taken together, this and future work will provide a greater understanding of how Bcc biofilms can be eradicated in order to improve existing antibiotic therapies and develop novel treatments, for patients with Cystic Fibrosis.