124 Lack of antimicrobial activity of ivacaftor against clinical CF respiratory isolates

Abstract

Objectives Ivacaftor contains a quinolone ring within its structure, similar to that of Ciprofloxacin. A previous study demonstrated that ivacaftor had some antimicrobial activity against laboratory and non-CF clinical isolates of S. aureus and S. pneumoniae . The aim of this study was to investigate the antimicrobial activity of ivacaftor against clinical respiratory CF isolates. Methods The MIC of ivacaftor against clinical isolates ( P. aeruginosa , S. aureus , Streptococcus sp.; n=5 from each genus) was determined using a radial diffusion assay. Bactericidal activity of ivacaftor against selected isolates growing planktonically and in biofilm was determined using a time-kill and a microtitre tray biofilm assay, respectively. Results were compared with ciprofloxacin. Results The radial diffusion assay indicated that ivacaftor had no bacteriostatic activity with an MIC of >50 mg/mL for all isolates tested. In time-kill assays bactericidal activity was observed for Streptococcus sp. only (Table 1). Ivacaftor had no effect on biofilm formation. Table 1Log change in CFU/mL (±SD) over 24 hours in time-kill assaysIvacaftor (32 mg/mL)Ciprofloxacin (5 mg/mL)ControlP. aeruginosa4.44±0.30−5.78±0.404.45±0.33S. aureus3.00±0.24−5.63±0.023.39±0.60Streptococcus sp.−3.17±2.26−4.50±1.353.75±0.51Achromobacter sp.2.83±0.27−1.63±3.843.01±0.17Stenotrophomonas sp.2.69±0.16−6.293.11±0.01 Conclusion Ivacaftor did not have a direct antimicrobial action against the clinical CF isolates tested, and did not slow the growth of isolates or inhibit biofilm formation. Work supported by a DEL NI studentship and a US-Ireland Project Partnership Grant.