In Vitro and In Vivo Efficacy of an LpxC Inhibitor, CHIR-090, Alone or Combined with Colistin against Pseudomonas aeruginosa Biofilm

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In vitro and in vivo Pharmacodynamics of Colistin and Aztreonam Alone and in Combination against Multidrug-Resistant Pseudomonas aeruginosa.

BACKGROUND Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study....

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Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli.

The deacetylation of UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine (UDP-3-O-acyl-GlcNAc) by LpxC is the committed reaction of lipid A biosynthesis. CHIR-090, a novel N-aroyl-l-threonine hydroxamic acid, is a potent, slow, tight-binding inhibitor of the LpxC deacetylase from the hyperthermophile Aquifex aeolicus, and it has excellent antibiotic activity against Pseudomonas aeruginosa and ...

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In vitro activity of Quercus brantii extracts against biofilm- producing Pseudomonas aeruginosa

Background: Biofilm formation by Pseudomonas aeruginosa is a serious concern in treatment of diseases and medical industries. Natural products that originate in plants can influence microbial biofilm formation. The effect of ethyl acetate, methanol and water- methanol extracts of Quercus brantii on biofilm formation and biofilm disruption of P. aeruginosa were investigated in this study. Methods...

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Activity of colistin combined with doripenem at clinically relevant concentrations against multidrug-resistant Pseudomonas aeruginosa in an in vitro dynamic biofilm model.

OBJECTIVES Colistin combination therapy may be required to treat biofilm-associated infections. We evaluated bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against biofilm-embedded and planktonic multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS One colistin-susceptible reference strain (PAO1) and two colistin-susceptible MDR clinical i...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2017

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.02223-16