Polymyxins: Antibacterial activity, resistance mechanisms and epidemiology of plasmid mediated resistance

The occurrence and spreading of multi-resistant, as well as pan-resistant bacterial isolates, presents a global problem of modern medicine. Narrowed therapeutic options actualized the use of "old" antibiotics such as polymyxins. The use of polymyxins in human medicine has been reduced since the 1960s due to the discovery of safer antibiotics. Modern researches provided a better understanding of their pharmacokinetics and pharmacodynamics, as well as dosing regimens with minimum side effects. However, the increased usage in therapy consequently led to the occurrence of resistance to these "last-line" antibiotics. Most of polymyxin resistant bacterial isolates carried chromosomally mediated resistance, but the discovery of the plasmid mcr-1 gene in 2015 in China changed the paradigm of the origin and spreading of polymyxin resistance. Animals are the main reservoirs of bacteria carrying plasmid with the mcr-1 gene, because of widespread polymyxins application in veterinary medicine and in food industry, as well. Many studies confirmed the transfer of polymyxins resistance genes from animal bacterial isolates to human isolates, as well as between different bacterial species in vivo or in vitro. These findings indicated the need for more detailed epidemiological research and surveillance, as the European Centre for Disease Prevention and Control recommended.