Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.

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Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

One Health is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and our environment. The drivers of antimicrobial resistance include antimicrobial use and abuse in human, animal, and environmental sectors and the spread of resistant bacteria and resistance determinants within and between these sectors and around the globe. Most of the classes of antimicrobials used to treat bacterial infections in humans are also used in animals. Given the important and interdependent human, animal, and environmental dimensions of antimicrobial resistance, it is logical to take a One Health approach when addressing this problem. This includes taking steps to preserve the continued effectiveness of existing antimicrobials by eliminating their inappropriate use and by limiting the spread of infection. Major concerns in the animal health and agriculture sectors are mass medication of animals with antimicrobials that are critically important for humans, such as third-generation cephalosporins and fluoroquinolones, and the long-term, in-feed use of medically important antimicrobials, such as colistin, tetracyclines, and macrolides, for growth promotion. In the human sector it is essential to prevent infections, reduce over-prescribing of antimicrobials, improve sanitation, and improve hygiene and infection control. Pollution from inadequate treatment of industrial, residential, and farm waste is expanding the resistome in the environment. Numerous countries and several international agencies have included a One Health approach within their action plans to address antimicrobial resistance. Necessary actions include improvements in antimicrobial use regulation and policy, surveillance, stewardship, infection control, sanitation, animal husbandry, and alternatives to antimicrobials. WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicrobials routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antimicrobials that are important for human medicine by reducing their use in animals.

Antimicrobial Resistance: a One Health Perspective.

Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.

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Antimicrobial resistance in Escherichia coli.

On 18 November 2015, Liu et al. reported the first description of plasmid-mediated colistin resistance (mcr-1 gene) in food animals, food and humans in China [1]. In this issue, Kluytmans-van den Bergh et al. report on their finding of the mcr-1 gene in Escherichia coli isolates from three (1.5%) of 196 samples of chicken meat collected at Dutch supermarkets, one in 2009 and two in 2014 [2]. This was done by whole genome sequencing of all E. coli isolates and then screening for the presence of the mcr-1 gene by comparing the assembled sequences with sequence data from two databases. The same study did not find any mcr-1-positive isolate among 2,275 extended-spectrum beta-lactamase-positive Escherichia coli (screening and clinical isolates) sampled in humans between 2009 and 2015. The exact origin of the sampled chicken meat was not known, with the two samples from 2014 being labelled ‘non-Dutch, European’. The fact that the genomes of the two isolates from 2014 differed by only three loci and were from the same lot of chicken meat strongly suggest cross-contamination from a common source.

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Plasmid-mediated colistin resistance (mcr-1 gene): three months later, the story unfolds

Molecular mechanisms of polymyxin resistance: knowns and unknowns

The recent identification of members of the family Enterobacteriaceae harboring the plasmid-mediated transferable colistin resistance mcr-1 gene is of great concern to public health ([1][1][–][2][4][3]). Here, we report on the occurrence of mcr-1 -harboring extended-spectrum β-lactamase (ESBL)-

Occurrence of the Plasmid-Borne mcr-1 Colistin Resistance Gene in Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in River Water and Imported Vegetable Samples in Switzerland.

Katrin Zurfuh

Papers

Occurrence of the Plasmid-Borne mcr-1 Colistin Resistance Gene in Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in River Water and Imported Vegetable Samples in Switzerland.