Use of colistin-containing products within the European Union and European Economic Area (EU/EEA): development of resistance in animals and possible impact on human and animal health

Catry, Boudewijn; Cavaleri, Marco; Baptiste, Keith E.; Grave, Kari; Grein, Kornelia; Holm, Anja; Jukes, Helen; Liébana, Ernesto; Navas, Antonio López; Mackay, D. K. J.; Magiorakos, Anna-Pelagia; Moreno, Miguel A.; Moulin, Gérard; Madero, Cristina Muñoz; Pomba, Maria Constança Matias Ferreira; Powell, M.; Pyörälä, Satu; Rantala, Merja; Ružauskas, Modestas; Sandérs, Pascal; Teale, Christopher; Threlfall, E. J.; Törneke, Karolina; Duijkeren, Engeline van; Edo, Jordi Torren

doi:10.1016/j.ijantimicag.2015.06.005

Cited by 206 publications

(170 citation statements)

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“…33 The detection of E. coli with the mcr-1 gene in a higher proportion of animal and raw meat samples relative to human clinical samples supports the notion that this resistance mechanism likely emerged in animals and subsequently spread to humans. It is speculated that the relative infrequency of mcr-1 among E. coli in Canada may relate to lower use of colistin among livestock in this country.…”

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confidence: 60%

Frequency of MCR-1-mediated colistin resistance among Escherichia coli clinical isolates obtained from patients in Canadian hospitals (CANWARD 2008-2015)

et al. 2016

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Background: Colistin is often used as an antimicrobial of last resort for the treatment of infections caused by multidrug-resistant gram-negative bacilli. In 2015, plasmid-mediated colistin resistance in Escherichia coli due to MCR-1 was described. The purpose of this study was to evaluate the frequency of colistin resistance among E. coli clinical isolates obtained from patients in Canadian hospitals as part of the Canadian Ward Surveillance Study (CANWARD) and to determine how often the mcr-1 gene is detected among the colistin-resistant subset. Methods:From January 2008 to December 2015 (excluding 2011), 10 to 15 sentinel hospitals submitted consecutive clinical isolates (1 per patient per infection site) from blood (100-240), respiratory (100-150), urine (25-100) and wound (25-100) infections. We performed susceptibility testing using Clinical and Laboratory Standards Institute broth microdilution methods. Isolates that showed resistance to colistin as defined by European Committee on Antimicrobial Susceptibility Testing breakpoints (minimum inhibitory concentration ≥ 4 µg/mL) were evaluated for the mcr-1 gene by polymerase chain reaction. Results:In total, 5571 E. coli clinical isolates were obtained over the study years. Twelve isolates (0.2%) were resistant to colistin. The proportion of colistin-resistant isolates varied from 0.0% to 0.5% depending on the study year, and there was no clear trend toward increasing resistance over time. Typically the colistin-resistant isolates remained susceptible to antimicrobials from several other classes. Two colistin-resistant isolates (0.04%) were found to harbour the mcr-1 gene. Interpretation:The results suggest that colistin resistance among E. coli human clinical isolates, including resistance mediated by the mcr-1 gene, remains rare in Canada. AbstractResearch Research CMAJ OPEN E642CMAJ OPEN, 4(4)to MCR-1. MCR-1 (encoded for by the mcr-1 gene) is a member of the phosphoethanolamine transferase enzyme family. It confers resistance to colistin by the transfer of phosphoethanolamine to lipid A, thereby reducing the affinity of the target (by reducing the negative charge) for this polycationic antimicrobial. 7 E. coli isolates with the mcr-1 gene typically have colistin minimum inhibitory concentrations (MICs) in the range of 4 to 8 µg/mL. 7-11The location of the mcr-1 gene on a plasmid is concerning, as this raises the possibility that the resistance determinant may be transferred to multidrug-resistant gram-negative bacteria. Indeed, the mcr-1 gene has already been detected in multidrugresistant E. coli isolates that also contain an extended-spectrum β-lactamase or a carbapenemase enzyme.12-15 Plasmid-mediated colistin resistance attributed to a second mcr gene (mcr-2) has also recently been described. 16 Many clinical microbiology laboratories do not test colistin routinely against E. coli, so the frequency with which resistance occurs in Canada is difficult to estimate from local data. The purpose of this study was to evaluate the frequency of colistin res...

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Frequency of MCR-1-mediated colistin resistance among Escherichia coli clinical isolates obtained from patients in Canadian hospitals (CANWARD 2008-2015)

et al. 2016

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“…The majority of polymyxin consumption corresponds to orally administered forms, with different formulations (premix, powder, or oral solutions). The main usage is related to enterobacterial infections, and in particular to gastrointestinal infections caused by E. coli in poultry and pigs within intensive husbandry systems (61). Apart from this common usage for treating infections caused by Enterobacteriaceae, another usage corresponds to growth promotion, which is a common practice worldwide.…”

Section: Use In Veterinary Medicinementioning

confidence: 99%

“…Furthermore, the fact that only a thin line exists between oral metaphylactic therapy, preventive starter rations, and growth promotion adds to the problem. In 2011, polymyxins were the fifth most sold class of antimicrobials (7%) for treating food-producing animals in Europe (61).…”

Section: Use In Veterinary Medicinementioning

confidence: 99%

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

2017

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SUMMARY 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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“…In veterinary medicine, colistin (polymyxin E) is used regularly for the treatment of gastrointestinal infections in livestock, whereas polymyxin B is topically applied for the treatment of otitis media and skin infections in small animals [1]. In human medicine, colistin has become one of the last-resort antimicrobials for treating lifethreatening infections caused by multidrug resistant (MDR) bacteria, and the emergence of plasmidmediated polymyxin resistance in Enterobacteriaceae severely compromises its use [2].…”

Section: Introductionmentioning

confidence: 99%

Investigation for the Colistin Resistance Genes mcr-1 and mcr-2 in Clinical Enterobacteriaceae Isolates from Cats and Dogs in Switzerland

2016

ARC Journal of Animal and Veterinary Sciences

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Colistin resistant Enterobacteriaceae have emerged in humans, food producing animals and food. The aim of this study was to assess the occurrence of MCR-1 and MCR-2 producers among Enterobacteriaceae isolated from companion animals admitted to the University of Zürich veterinary clinic. A total of 347 isolates (231 from dogs, 116 from cats) were analysed. Thereof, 274 (79%) were from urine and 73 (21%) from surgical sites, abscesses and other sources. All isolates were screened by polymerase chain reaction (PCR) for the presence of the plasmid-mediated colistin resistance genes mcr1and mcr-2. Phenotypic colistin resistance was screened for by the antibiotic broth microdilution method. None of the isolates tested positive by PCR for the mcr-1 or the mcr-2 gene. Broth microdilution tests revealed MICs of 2mg/L-64 mg/L of colistin for four isolates (two Enterobacter spp., one Klebsiella spp. and one E. coli) from dogs (one from skin exudate, one from a surgical site and two isolates from urine). This study documents the presence of non-transmissible colistin resistance in clinical isolates from dogs and cats and confirms that so far, companion animals in Switzerland do not represent a reservoir for plasmid-mediated colistin resistant Enterobacteriaceae.

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Use of colistin-containing products within the European Union and European Economic Area (EU/EEA): development of resistance in animals and possible impact on human and animal health

Cited by 206 publications

References 98 publications

Frequency of MCR-1-mediated colistin resistance among Escherichia coli clinical isolates obtained from patients in Canadian hospitals (CANWARD 2008-2015)

Frequency of MCR-1-mediated colistin resistance among Escherichia coli clinical isolates obtained from patients in Canadian hospitals (CANWARD 2008-2015)

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

Investigation for the Colistin Resistance Genes mcr-1 and mcr-2 in Clinical Enterobacteriaceae Isolates from Cats and Dogs in Switzerland

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