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Title: In Vitro and In Vivo Efficacy of an LpxC Inhibitor, CHIR-090, Alone or Combined with Colistin against Pseudomonas aeruginosa Biofilm
Authors: Tan, Jun Hou
Vidaillac, Celine
Yam, Joey Kuok Hoong
Chua, Song Lin
Givskov, Michael
Yang, Liang
Keywords: LpxC inhibitor
Pseudomonas aeruginosa
Issue Date: 2017
Source: Tan, J. H., Vidaillac, C., Yam, J. K. H., Chua, S. L., Givskov, M., & Yang, L. (2017). In Vitro and In Vivo Efficacy of an LpxC Inhibitor, CHIR-090, Alone or Combined with Colistin against Pseudomonas aeruginosa Biofilm. Antimicrobial Agents and Chemotherapy, 61(7), e02223-16-.
Series/Report no.: Antimicrobial Agents and Chemotherapy
Abstract: With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined with CHIR-090, a potent LpxC inhibitor, against in vitro and in vivo Pseudomonas aeruginosa biofilms. Four P. aeruginosa isolates with various colistin susceptibilities were chosen for evaluation. The tested isolates of P. aeruginosa exhibited MIC values ranging from 1 to 64 and 0.0625 to 0.5 μg/ml for colistin and CHIR-090, respectively. Against 24-h static biofilms, minimum biofilm eradication concentration values ranged from 256 to 512 and 8 to >128 μg/ml for colistin and CHIR-090, respectively. Interestingly, subinhibitory concentrations of CHIR-090 contributed to the eradication of subpopulations of P. aeruginosa with the highest colistin MIC values. The combination of colistin and CHIR-090 at subinhibitory concentrations demonstrated synergistic activity both in vivo and in vitro and prevented the formation of colistin-tolerant subpopulations in in vitro biofilms. In summary, our study highlights the in vivo and in vitro synergistic activity of the colistin and CHIR-090 combination against both colistin-susceptible and -nonsusceptible P. aeruginosa biofilms. Further studies are warranted to investigate the clinical relevance of the combination of these two antimicrobials and outline the underlying mechanism for their synergistic action.
ISSN: 0066-4804
DOI: 10.1128/AAC.02223-16
Rights: © 2017 American Society for Microbiology. This paper was published in Antimicrobial Agents and Chemotherapy and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The published version is available at: []. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
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