An overview of colistin resistance, mobilized colistin resistance genes dissemination, global responses, and the alternatives to colistin: A review

Abstract

Colistin, also known as polymyxin E, is an antimicrobial agent that is effective against a variety of Gram-negative bacilli, especially the Enterobacteriaceae family. Recently, the wide dissemination of colistin-resistance has brought strong attention to the scientific society because of its importance as the last resort for the treatment of carbapenem-resistant Enterobacteriaceae infections and its possible horizontal transmission. The mobilized colistin resistance (mcr) gene was identified as the gene responsible for unique colistin resistance. Indeed, despite many studies that have revealed a pan variation in the existence of this gene, not only for the mcr genes main group but also for its many subgroups, the problem is growing and worsening day after day. In this regard, this review paper is set to review the updated data that has been published up to the end of 2019 third quarter, especially when related to colistin resistance by the mcr genes. It will include the present status of colistin resistance worldwide, the mcr gene dissemination in different sectors, the discovery of the mcr variants, and the global plan to deal with the threat of antimicrobial resistance. In line with global awareness, and to stop antibiotic misuse and overuse, especially in agricultural animals, the study will further discuss in detail the latest alternatives to colistin use in animals, which may contribute to the elimination of inappropriate antibiotic use and to the help in preventing infections. This review will advance our understanding of colistin resistance, while supporting the efforts toward better stewardship, for the proper usage of antimicrobial drugs in humans, animals, and in the environment.

High abundance of the colistin resistance gene mcr-1 in chicken gut-bacteria in Bangladesh

“…On the other hand, a significant portion of isolates without carrying any detectable mcr gene, showed phenotypic resistance to colistin. The inconsistency of the genotype-phenotype association could be explained by other variants of mcr genes or factors that have not been investigated in this study 21 .…”

“…After that, multiple mcr-1 -carrying species of Enterobacteriaceae were detected in many countries in the environment, animals, and humans 17 – 19 . Subsequently, more variants of transferable colistin resistance mcr gene ( mcr-1 to mcr-9 ) have been described in Enterobacteriaceae 20 , 21 . As colistin was extensively used in animal production in China, increased colistin resistance has been observed there in recent years 18 , 22 .…”

Bibliometric analysis of Scopus indexed publications on polymyxin resistance (2009-2018)

“…Second, it was not possible to discern between articles related to humans and animals. Despite this, the relationship is closer than it seems because colistin is used as a growth promoter in the veterinary eld [43]. Furthermore, horizontal transmission of mcr genes occurs through multi-resistance plasmids from animals, humans, and retail meat [43,44].…”

A New Era of Antibiotics: The Clinical Potential of Antimicrobial Peptides

“…A variety of factors have led to the progressive increase in antibiotic resistant bacteria; however, they all narrow down to the over-reliance on antibiotics. The use of antibiotics in agriculture and the environment is largely unregulated; only when resistance is widespread are certain antibiotics prohibited [ 7 ]. Alarmingly, 80% of all antibiotics are consumed by animals, with the remaining 20% for human use [ 8 ].…”

“…For example, colistin is a last-resort antibiotic for the treatment of unresponsive multidrug-resistant infections. However, its widespread use in agriculture has propelled the emergence of the mobilized colistin-resistance ( mcr ) gene, with enormous implications for the treatment of human infection [ 7 ]. Without action, history suggests we will see our remaining effective antibiotics suffer similar fates.…”