742. Low dose nitric oxide as adjunctive therapy to treat chronic Pseudomonas aeruginosa infection in cystic fibrosis
Session: Poster Abstract Session: Antimicrobials: Resistance Mechanisms
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 130921 Katrina Cathie ID week.png (1.6 MB)
  • Background: The presence of bacterial biofilms in the lower airways and their antimicrobial tolerance is important in the pathogenesis of chronic lung infection in cystic fibrosis (CF). Recently, a key role for nitric oxide (NO) in the natural process of dispersal of biofilms has been described. As such, the application of NO to CF biofilms represents a potentially novel adjunctive therapy to conventional antibiotics.

    Methods: Ex vivo clinical isolates of P. aeruginosa were obtained from cystic fibrosis patient sputum samples and biofilms were investigated. Dispersal and antibiotic sensitivity were assessed by a combination of laboratory methods (including colony forming units, FISH and quantitative PCR) in response to low (nanomolar, non-bactericidal) dose NO as sodium nitroprusside (SNP) or DEA-CP, a novel NO releasing antibiotic compound.

    Results: P. aeruginosa biofilms were dispersed on treatment with nanomolar concentrations of NO and with DEA-CP. Biofilm dispersal was NO concentration dependent and accompanied by the dissociation of surface-bound biofilm into the planktonic suspension. Moreover, biofilm dispersal was accompanied by an increased susceptibility of P. aeruginosa to clinically relevant antibiotics such as tobramycin and ceftazadime. Tobramycin alone caused increase in P. aeruginosa biofilm growth.

    Conclusion: NO-mediated dispersal delivered in vitro directly (SNP) or via a novel NO donor (DEA-CP) compound ameliorates P. aeruginosa antibiotic resistance mechanisms associated with clinical biofilms. We are in the process of completing a proof-of-principle clinical trial to investigate NO as adjunctive therapy in CF (EudraCT 2010-023529-39).

    Katrina Cathie, BM (Hons), MRCPCH1, Robert Howlin, PhD2, Priya Sukhtankar, MRCPCH3, Caroline Duignan, MSc2, Sandra Pink, BA4, Caroline Smith, RN4, Johanna Jefferies, PhD, MFPH5, Rami Salib, PhD FRCS(ORL-HNS)4, Mary Carroll, MD FRCP6, Julian Legg, MD FRCPCH1, Thomas Daniels, MRCP DM6, Gary Connett, MD FRCPCH1, Nicolas Barraud, PhD7, Scott Rice, PhD8,9, Michael Kelso, PhD10, Staffan Kjelleberg, PhD8,11, Paul Stoodley, PhD12, Luanne Hall-Stoodley, PhD13, Stuart Clarke, PhD FFPH FRCPath5, Jeremy Webb, PhD2 and Saul Faust, MBBS MRCPCH PhD13,14, (1)Child Health, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom, (2)School Of Biological Sciences, University of Southampton, Southampton, United Kingdom, (3)Nihr Wellcome Trust Clinical Research Facilities, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom, (4)Southampton Nihr Biomedical Research Unit, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom, (5)Clinical and Experimental Sciences, Faculty Of Medicine, University of Southampton, Southampton, United Kingdom, (6)Adult Cystic Fibrosis Department, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom, (7)School of Biotechnology and Biomolecular Sciences, University of New South Wales and Centre for Marine Bio-Innovation, Sydney, Australia, (8)The Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore, (9)Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, (10)School of Chemistry, University of Wollongong, Wollongong, Australia, (11)School of Biotechnology and Biological Sciences and Centre for Marine Bio-Innovation, University of New South Wales, Sydney, Australia, (12)University of Southampton, Southampton, United Kingdom, (13)Nihr Wellcome Trust Clinical Research Facilities, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, (14)Nihr Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    Disclosures:

    K. Cathie, None

    R. Howlin, None

    P. Sukhtankar, None

    C. Duignan, None

    S. Pink, None

    C. Smith, None

    J. Jefferies, None

    R. Salib, None

    M. Carroll, None

    J. Legg, None

    T. Daniels, None

    G. Connett, None

    N. Barraud, None

    S. Rice, None

    M. Kelso, None

    S. Kjelleberg, None

    P. Stoodley, None

    L. Hall-Stoodley, None

    S. Clarke, None

    J. Webb, None

    S. Faust, None

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