The anthelmintic oxyclozanide restores the colistin activity in colistin-resistant Gram-negative bacilli.

08:00 EDT 9th July 2019 | BioPortfolio

Summary of "The anthelmintic oxyclozanide restores the colistin activity in colistin-resistant Gram-negative bacilli."

Due to the significant increase in the antimicrobial resistance of Gram-negative bacilli (GNB), the development of non-antimicrobial therapeutic alternatives, which can be used together with the few and non-optimal available antimicrobial agents such as colistin, has become an urgent need. In this context, the desregulation of the bacterial cell wall could be a therapeutic alternative adjuvant to colistin. The aim of this study was to analyse the activity of oxyclozanide, an anthelmintic drug, in combination with colistin against colistin-susceptible (Col-S) and colistin-resistant (Col-R) GNB. Three reference Col-S strains and 13 Col-R clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae were studied. Microdilution assays and time-kill curves were performed to examine the activity of oxyclozanide in combination with colistin. Outer membrane proteins (OMPs) profile, membrane permeation and cell wall structure of Col-S and Col-R A. baumannii, P. aeruginosa and K. pneumoniae in presence of oxyclozanide were assessed by SDS-PAGE, fluorescence and transmission electron microscopy, respectively. Oxyclozanide in combination with colistin increases the activity of colistin against Col-S and Col-R A. baumannii, P. aeruginosa and K. pneumoniae. Time-killing curves have showed synergistic activity between oxyclozanide and colistin against these bacterial isolates. Moreover, Col-R A. baumannii, P. aeruginosa and K. pneumoniae in presence of oxyclozanide present higher permeation and disruption in their cell wall than Col-S strains, without modifying their OMPs profile. These data suggest that the combination of oxyclozanide and colistin may be a new alternative for the treatment of Col-R GNB infections.


Journal Details

This article was published in the following journal.

Name: International journal of antimicrobial agents
ISSN: 1872-7913


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Medical and Biotech [MESH] Definitions

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A semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.

A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms.

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