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Garlic as an inhibitor of pseudomonas aeruginosa quorum sensing in cystic fibrosis - A pilot randomized controlled trial

Smyth, Alan R.; Cifelli, Paramita M.; Ortori, Catharine A.; Righetti, Karima; Lewis, Sarah; Erskine, Penny; Holland, Elaine D.; Givskov, Michael; Williams, Paul; Cámara, Miguel; Barrett, David A.; Knox, Alan

Authors

Alan R. Smyth

Paramita M. Cifelli

Catharine A. Ortori

Karima Righetti

Penny Erskine

Elaine D. Holland

Michael Givskov

PAUL WILLIAMS PAUL.WILLIAMS@NOTTINGHAM.AC.UK
Professor of Molecular Microbiology

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MIGUEL CAMARA MIGUEL.CAMARA@NOTTINGHAM.AC.UK
Professor of Molecular Microbiology

David A. Barrett

Alan Knox



Abstract

Pseudomonas aeruginosa forms biofilms in the cystic fibrosis lung. Quorum sensing (QS) controls biofilm maturation, immune evasion, antibiotic tolerance and virulence factor production. Garlic shows QS inhibitory activity in vitro and in animal models. We report the first clinical trial in man of a QS inhibitor. We randomized 34 patients to garlic or olive oil capsules (both 656mgdaily). Clinical outcomes and safety bloods were measured at baseline and after 8 weeks treatment. In this exploratory study, analysis was per protocol. Eight patients withdrew, leaving 26 for analysis (13 garlic). With placebo, there was a greater decline in mean (SD) percentage change from baseline FEV1[-3.6% (11.3)] than with garlic [-2.0% (12.3)]. This was not significant (mean difference = 1.6, 95% CI -12.7 to 15.9, P = 0.8). The mean (SD) increase in weight was greater with garlic [1.0% (2.0)] than with placebo [0.6% (2.0)] - non-significant (mean difference = 0.4%, 95% CI -1.3 to 2.0, P = 0.6). The median (range) change in clinical score with garlic was -1 (-3 to 5) and 1 (-1 to 4) with placebo (negative score means improvement). Thiswas non-significant [median difference = -1 (-3 to 0), P = 0.16]. In the garlic group, seven patients had IV antibiotics versus five placebo. There was a highly significant correlation between plasma and sputum measurements of the QS molecule 3-oxo-C12-HSL (Pearson correlation coefficient = 0.914, P = 0.004). At the end of treatment five patients in each group had abnormal liver function or triglycerides and five garlic patients (one placebo) reported minor adverse effects. Garlic capsules were well tolerated. Although there was no significant effect of garlic compared to placebo in this pilot study, there was a suggestion of improvement with garlic which should be investigated in a larger trial. © 2010 Wiley-Liss, Inc.

Journal Article Type Article
Acceptance Date Nov 9, 2009
Online Publication Date Mar 19, 2010
Publication Date Apr 1, 2010
Deposit Date Apr 21, 2023
Journal Pediatric Pulmonology
Print ISSN 8755-6863
Electronic ISSN 1099-0496
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 45
Issue 4
Pages 356-362
DOI https://doi.org/10.1002/ppul.21193
Public URL https://nottingham-repository.worktribe.com/output/3105084
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.21193