On the edge of a precipice: the global emergence and dissemination of plasmid-borne mcr genes that confer resistance to colistin, a last-resort antibiotic

Abstract Colistin (polymyxin E) is used as a last-resort antibiotic to treat complicated infections with gram-negative bacteria. However, global dissemination of transmissible plasmid-borne resistance to colistin has been reported recently. This can potentially severely limit the treatment of multidrug-resistant infections, which has raised public health concerns. Despite the attention, data on colistin resistance and the plasmid-borne mobile colistin-resistance genes (mcr) remain scarce in countries with developing antimicrobial stewardship. The latter applies to many countries in the Middle East and North Africa (MENA) region, where the use of antibiotics in human medicine and conventional farming practices is not necessarily well regulated. Furthermore, many MENA countries have witnessed calamitous events such as wars, loss of vital resources and infrastructure, and displacement of large populations (refugees), while the region hosts many of the largest multinational religious gatherings in the world. These conditions are ideal for the emergence and transmission of multidrug-resistant pathogens as well as resistance-encoding genes. Subsequently, monitoring the efficacy of last-resort antibiotics such as colistin in the MENA region is of paramount importance to local and global health. Here, we review available data on mcr and associated colistin resistance globally. We have also mapped the occurrence and sources of different mcr genes in the MENA region for the first time. We conclude that there is a need for more surveillance and analysis of transmission routes of these genes worldwide and that emphasis should be placed on resource-limited countries like those in the MENA region. We argue that the latter is essential in order to curb the global spread of mcr-associated colistin resistance.