A time kill assay showed a bactericidal effect of the CO–CCCP combination. In contrast, VRP, PAβN and RSP did not restore CO susceptibility. intermedia, supporting an efflux pump mechanism. Using the broth microdilution method, a CO and CCCP combination of 2 µg/mL and 10 µg/mL, respectively, significantly reduced the CO minimal inhibitory concentration (MIC) of B. intermedia, we evaluated the effects of verapamil (VRP), reserpine (RSP), phe-arg β-naphthylamide dihydrochloride (PAβN) and carbonyl cyanide 3-chloro phenyl hydrazone (CCCP), four efflux pump inhibitors, on these colistin-resistant strains. In order to determine whether an efflux pump mechanism was involved in CO resistance in B. We isolated six Brucella intermedia strains from Senegalese monkey stool. It is naturally resistant to polymyxins, including colistin (CO), and may cause opportunistic infections in humans. Further work is necessary to identify new EPIs that could be used in humans.īrucella intermedia (formerly Ochrobactrum intermedium), a non-fermentative bacterium, has been isolated from animals and human clinical specimens. EPIs could be an alternative for restoring colistin activity in Gram-negative bacteria. 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. A time-kill study showed the combination was bacteriostatic on strains tested. The same was true for bacteria with a heteroresistance mechanism compared to bacteria with other colistin resistance mechanisms (P < 0.0001). Proteus spp., Serratia marcescens, Morganella morganii and Providencia spp.) than on other Enterobacteriaceae (P < 0.0001). The effect of CCCP was significantly greater on intrinsically colistin-resistant bacteria (i.e. Overall, CCCP was able to reverse colistin resistance for all strains tested. In order to evaluate the effect of this combination, a time-kill study was performed on five strains carrying different colistin resistance mechanisms. 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.Ĭolistin MIC was evaluated with and without CCCP and the fold decrease of colistin MIC was calculated for each strain. 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. Efflux in bacteria is a ubiquitous mechanism associated with resistance to antimicrobials agents.
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