Global colistin use: a review of the emergence of resistant Enterobacterales and the impact on their genetic basis

Abstract

The dramatic global rise of MDR and XDR Enterobacterales in human medicine forced clinicians to the reintroduction of colistin as last-resort drug. Meanwhile, colistin is used in the veterinary medicine since its discovery leading to a steadily increasing prevalence of resistant isolates in the livestock and meat-based food sector. Consequently, transmission of resistant isolates from animals to humans, acquisition via food, and exposure to colistin in the clinic are reasons for the increased prevalence of colistin-resistant Enterobacterales in humans in the last decades. Initially, resistance mechanisms were caused by mutations in chromosomal genes. However, since the discovery in 2015, the focus has shifted exclusively to mobile colistin resistances (mcr). This review will advance the understanding of chromosomal-mediated resistance mechanisms in Enterobacterales. We provide an overview about genes involved in colistin resistance and the current global situation of colistin-resistant Enterobacterales. A comparison of the global colistin use in veterinary and human medicine highlights the effort to reduce colistin sales in veterinary medicine under the One Health approach. In contrast, it uncovers the alarming rise in colistin consumption in human medicine due to the emergence of MDR Enterobacterales, which might be an important driver for the increasing emergence of chromosome-mediated colistin resistance.

Genomic Analysis of ESBL-Producing E. coli in Wildlife from North-Eastern Germany

“…Antimicrobials are used in livestock production to treat individual animals. Besides, they Antibiotics 2022, 11, 123 2 of 15 are also administered for the treatment of whole groups, herds or flock, if clinical disease occurs in a small number of animals (metaphylactic approach) [8,9].…”

“…However, the broad use of antimicrobials—for example, in pig farming—is still ongoing [ 7 ]. Tetracyclines, amoxicillin, macrolides and colistin are most frequently used in pork production [ 8 ]. Antimicrobials are used in livestock production to treat individual animals.…”

Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)

“…Although the small use in human medicine in the past due to neurotoxicity and nephrotoxicity, COL has been widely used in veterinary medicine to promote animal growth in the livestock and seafood industry [ 1 ]. The recent rise in COL consumption in human medicine due to the emergence of MDR Enterobacterales and the overuse and/or misuse of COL among animals have led to the global emergence of COL-resistant (COL-R) pathogens [ 2 ].…”

Polymyxin B1 within the E. coli cell envelope: insights from molecular dynamics simulations

“…Ultimately, it is desirable to go beyond a mechanistic understanding of polymyxins such that computational methods can be employed to inform the design of novel, more potent antibiotics, particularly as resistance to polymyxins has now emerged. (Binsker et al 2021;Jeannot et al 2017) To achieve this, calculations that provide quantitative comparisons of, e.g. free energies of membrane permeation of de novo designed candidate antibiotics are required.…”