Imperial College London
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ProfessorVictoriaCornelius

Faculty of Medicine, School of Public Health

Professor in Medical Statistics and Trials Methodology
 
 
 
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Contact

 

+44 (0)20 7594 1218v.cornelius

 
 
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Assistant

 

Mrs Ranjit Rayat +44 (0)20 7594 3445

 
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Location

 

111Stadium HouseWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Howlin:2017:10.1016/j.ymthe.2017.06.021,
author = {Howlin, RP and Cathie, K and Hall-Stoodley, L and Cornelius, V and Duignan, C and Allan, RN and Fernandez, BO and Barraud, N and Bruce, KD and Jefferies, J and Kelso, M and Kjelleberg, S and Rice, SA and Rogers, GB and Pink, S and Smith, C and Sukhtankar, PS and Salib, R and Legg, J and Carroll, M and Daniels, T and Feelisch, M and Stoodley, P and Clarke, SC and Connett, G and Faust, SN and Webb, JS},
doi = {10.1016/j.ymthe.2017.06.021},
journal = {MOLECULAR THERAPY},
pages = {2104--2116},
title = {Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis},
url = {http://dx.doi.org/10.1016/j.ymthe.2017.06.021},
volume = {25},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases.
AU  - Howlin,RP
AU  - Cathie,K
AU  - Hall-Stoodley,L
AU  - Cornelius,V
AU  - Duignan,C
AU  - Allan,RN
AU  - Fernandez,BO
AU  - Barraud,N
AU  - Bruce,KD
AU  - Jefferies,J
AU  - Kelso,M
AU  - Kjelleberg,S
AU  - Rice,SA
AU  - Rogers,GB
AU  - Pink,S
AU  - Smith,C
AU  - Sukhtankar,PS
AU  - Salib,R
AU  - Legg,J
AU  - Carroll,M
AU  - Daniels,T
AU  - Feelisch,M
AU  - Stoodley,P
AU  - Clarke,SC
AU  - Connett,G
AU  - Faust,SN
AU  - Webb,JS
DO  - 10.1016/j.ymthe.2017.06.021
EP  - 2116
PY  - 2017///
SN  - 1525-0016
SP  - 2104
TI  - Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis
T2  - MOLECULAR THERAPY
UR  - http://dx.doi.org/10.1016/j.ymthe.2017.06.021
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000410462600013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/52973
VL  - 25
ER  -
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