Carbapenem and colistin resistance in Enterobacteriaceae: worldwide spread and future perspectives

Abstract

Carbapenems and colistin antibiotics are the major weapons against multidrug-resistant (MDR) and extensively drug-resistant Gram-negative bacteria. Escherichia coli , Klebsiella pneumoniae , Enterobacter cloacea , Klebsiella oxytoca , Proteus mirabilis , Citrobacter freundii , Citrobacter koseri , Serratia spp., Morganella morganii and Salmonella spp. have been reported as carbapenemase-producing Enterobacteriaceae members. Carbapenem resistance mostly occurs by means of some enzymes such as classes A, B and D carbapenemases. New Delhi metallo-β-lactamases, K. pneumoniae carbapenemase, imipenemase metallo-β-lactamase, Verona integron-encoded metallo-β-lactamase and OXA-48-like subtypes have been reported worldwide with some epidemiological differences. Plasmid-mediated transmission has facilitated their spread. In addition, colistin resistance by means of either chromosomal mutation in one of the three genes involved in the biosynthesis of LipA, LpxA, LpxC and LpxD cell wall components or via extrachromosomal elements (plasmid-mediated mcr genes) has recently reported in some species worldwide. MDR and extensively drug-resistant strains have become nonsusceptible to last-line antibiotics, thus consideration of effective ways such as the implementation of appropriate infection control strategies, separation of patients infected with MDR strains from others, public education, containment of antibiotic consumption in livestock industry, accurate antibiotic susceptibility testing and prescription and the proper implementation of antibiotic surveillance in hospitals are necessary. In addition, the use of last-line antibiotics in livestock and food animals must be restricted or banned.