+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Efflux pump inhibitor CCCP to rescue colistin susceptibility in mcr-1 plasmid-mediated colistin-resistant strains and Gram-negative bacteria

Efflux pump inhibitor CCCP to rescue colistin susceptibility in mcr-1 plasmid-mediated colistin-resistant strains and Gram-negative bacteria

Journal of Antimicrobial ChemoTherapy 2018

Efflux in bacteria is a ubiquitous mechanism associated with resistance to antimicrobials agents. Efflux pump inhibitors (EPIs) have been developed to inhibit efflux mechanisms and could be a good alternative to reverse colistin resistance, but only CCCP has shown good activity. The aim of our study was to identify CCCP activity in a collection of 93 Gram-negative bacteria with known and unknown colistin resistance mechanisms including isolates with mcr-1 plasmid-mediated colistin resistance. Colistin MIC was evaluated with and without CCCP and the fold decrease of colistin MIC was calculated for each strain. In order to evaluate the effect of this combination, a time-kill study was performed on five strains carrying different colistin resistance mechanisms. Overall, CCCP was able to reverse colistin resistance for all strains tested. The effect of CCCP was significantly greater on intrinsically colistin-resistant bacteria (i.e. Proteus spp., Serratia marcescens, Morganella morganii and Providencia spp.) than on other Enterobacteriaceae (Pā€Š<ā€Š0.0001). The same was true for bacteria with a heteroresistance mechanism compared to bacteria with other colistin resistance mechanisms (Pā€Š<ā€Š0.0001). A time-kill study showed the combination was bacteriostatic on strains tested. These results suggest an efflux mechanism, especially on intrinsically resistant bacteria and Enterobacter spp., but further analysis is needed to identify the molecular support of this mechanism. EPIs could be an alternative for restoring colistin activity in Gram-negative bacteria. Further work is necessary to identify new EPIs that could be used in humans.

(PDF emailed within 0-6 h: $19.90)

Accession: 060857300

Download citation: RISBibTeXText

PMID: 29718423

DOI: 10.1093/jac/dky134

Related references

Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria. Antimicrobial Agents and ChemoTherapy 60(5): 3215-3218, 2017

New therapy from old drugs: synergistic bactericidal activity of sulfadiazine with colistin against colistin-resistant bacteria, including plasmid-mediated colistin-resistant mcr-1 isolates. International Journal of Antimicrobial Agents 51(5): 775-783, 2018

Activity of the colistin-rifampicin combination against colistin-resistant, carbapenemase-producing Gram-negative bacteria. Journal of ChemoTherapy 26(4): 211-216, 2015

Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet. Infectious Diseases 18(4): 391-400, 2018

Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins. Antimicrobial Agents and ChemoTherapy 61(8), 2017

Activity of the type I signal peptidase inhibitor MD3 against multidrug-resistant Gram-negative bacteria alone and in combination with colistin. Journal of Antimicrobial ChemoTherapy 69(12): 3236-3243, 2015

Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens. Frontiers in Microbiology 9: 1808, 2018

Colistin resistance in gram-negative bacteria during prophylactic topical colistin use in intensive care units. Intensive Care Medicine 39(4): 653-660, 2013

Bacteraemia in cancer patients caused by colistin-resistant Gram-negative bacilli after previous exposure to ciprofloxacin and/or colistin. Clinical Microbiology and Infection 12(5): 497-498, 2006

Safety and efficacy of intravenous colistin (colistin methanesulphonate) for severe multidrug-resistant Gram-negative bacterial infections. International Journal of Antimicrobial Agents 35(3): 297-300, 2010

Effectiveness and nephrotoxicity of colistin monotherapy vs. colistin-meropenem combination therapy for multidrug-resistant Gram-negative bacterial infections. Clinical Microbiology and Infection 12(12): 1227-1230, 2006

Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrobial Agents and ChemoTherapy 53(8): 3430-3436, 2009

Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria. Chest 144(6): 1768-1775, 2014

Colistin Dosage without Loading Dose Is Efficacious when Treating Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia Caused by Strains with High Susceptibility to Colistin. Plos One 11(12): E0168468, 2017

Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria. International Journal of Antimicrobial Agents 25(1): 11-25, 2004