Émergence de la résistance à la colistine chez les entérobactéries : une brèche dans le dernier rempart contre la pan-résistance !

The fight against multidrug-resistant (MDR) bacteria is a major public health challenge. This challenge is well illustrated by the dissemination of carbapenemase-producing Enterobacteriaceae (CPE) that usually remains susceptible only to colistin. Colistin is widely used in veterinary medicine for the treatment of Gram-negative bacilli related infections in livestock. At the opposite, this molecule has longtime been ruled out of treatment protocols due to its kidney toxicity. Nowadays, colistin is prescribed again, as a last resort antimicrobial therapy for the treatment of severe infections caused by extremely drug-resistant bacteria, such as CPE. Unfortunately, in countries where CPE prevalence is high, such as Greece or Italy, the resistance to colistin is increasing. In most of the case, this resistance results of modifications in chromosome encoded genes leading to modifications of the lipopolysaccharide (LPS) global charge, consequently impairing the fixation of the colistin. Recently, plasmid-mediated resistance to colistin, due to mcr-1 and mcr-2 genes, has been described in Enterobacteriaceae (Escherichia coli, Salmonella…). MCR-producing isolates have been reported in East Asia, South America, Africa and Europe (Denmark, United-Kingdom, France, Portugal…). Most of these mcr-positive isolates are E. coli that have been recovered from animals and rarely from human samples. The emergence and spread of plasmid-mediated resistance to colistin is worrisome since it compromises the last bastion on the way to pan-drug resistance. This threatening perspective is stressed by the fact that the pipeline and the prospect of new antimicrobial molecules are quite limited.