140 Towards the clinical application of anti-pseudomonal bacteriophages: Activity is retained following nebulisation with a range of commercially available nebuliser systems

Abstract

Objectives We have recently established efficacy of nasally-inhaled phage against P. aeruginosa in a murine model with reduced infective burden and inflammatory response (2013 ECFC Abstract 17.3). The aim of this study was to assess phage activity and titre after exposure to nebuliser systems more applicable to clinical use. Methods Four different phage (1–4) were nebulised through Pari LC Plus (LCP), Aeroeclipse II (AE) and eFlow Rapid for up to 15 min. Phage were collected downstream and titres quantified by assessing efficacy on standard plaque assay. Results were compared with phage exposed to non-functioning nebuliser chambers. Results All phage retained efficacy post-nebulisation. Nebuliser type affected recovered titres: •LCP caused significant decrease in titres of phage 1 and 2 within 5 min and phage 3 within 15 min (p •AE, despite similar mode of action to LCP, was not as detrimental to titres. Decrease in phage 1 titre was seen within 15 min, phage 2 within 10 min (p 0.05). •eFlow does not continuously nebulise and recirculate phage, hence changes in titre over time were not recorded. No titre decreases were observed at end of nebulisation (p> 0.05). •Morphology may play a role in maintenance of phage titre post-nebulisation (1 and 2 myoviridae, 3 and 4 podoviridae). Conclusions Phage efficacy was retained after nebulisation though titres dropped, greatest for LCP and least for eFlow (which fell within variability of the methodology (0.5 log)). We confirm that phage can survive nebulisation and that this mode of administration may therefore be appropriate for future clinical trials.