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The Canadian Food Inspection Agency is developing an Establishment-based Risk Assessment (ERA) model for commercial and on-farm mills involved in the manufacture, storage, packaging, labeling, or distribution of livestock feed (ERA-Feed Mill model). This model will help inform the allocation of inspection resources on the basis of feed safety risk, including animal health and food safety risk. In a previous study, 34 risk factors, grouped into inherent, mitigation, and compliance clusters, along with assessment criteria were selected. The objective of this current study was to estimate the relative risk (RR) of the 203 assessment criteria on the basis of the impact on feed safety to design an ERA-Feed Mill model algorithm. Furthermore, the intent of this study was to assess the maximum increase or decrease of risk obtained when multiple criteria belonging to a same cluster were identified in a specific feed mill. To do so, a two-round face-to-face expert elicitation was conducted with 28 Canadian feed experts. Results showed no significant association between respondent profiles (years of experience and work sector) and estimated RR. Uniformity of answers between experts improved between rounds. Criteria having the highest increase in risk (median RR ≥ 4) included the presence of materials prohibited to be fed to ruminants in a facility that produces ruminant feed, the presence of multiple livestock species on-site, and historical noncompliances related to the inspection of the feed mill's process control and end-product control programs. Risk mitigation criteria having the highest impact on decreasing the risk were the implementation of feed safety certifications, the use of dedicated manufacturing lines (prohibited materials or medications), and having a hazard sampling plan in place for finished feed. The median RR assigned to each criterion and cluster will be used to build an algorithm of the Canadian Food Inspection Agency's ERA-Feed Mill model. HIGHLIGHTS

Agricultural practices such as manure applications could contribute to the spread of antibiotic resistance genes (ARGs) within the environment. Our objective was to assess the impact of certain fertilization methods (mineral or manure) and tillage practices (reduced or conventional) on the presence of ARGs and bacteria in soil and drainage water under wheat and grain corn crops. Targeted ARGs tet(T), sul1, and blaCTX-M-1 in liquid hog manure, soil, and water samples were quantified by qPCR. Conventional PCR was used to detect mcr-1 and mcr-2. ARGs in control plots were detected despite the absence of manure, representing an environmental reservoir of resistant microorganisms. The manure application rate higher than 39 m3/ha increased tet(T) and sul1 gene concentrations in soil for more than 180 days. Tillage practices had no impact on ARG concentrations in soil and water samples. The blaCTX-M-1 gene was only detected in seven water samples in 2016, but no link was established with the treatments. The mcr-1 and mcr-2 genes were not detected in all tested samples. This study demonstrated that tet(T) and sul1 gene concentrations increased in soil after liquid hog manure application as well as in drainage water in the next weeks.

The intestinal microbiota plays several important roles in pig health and growth. The aim of the current study was to characterize the changes in the fecal microbiota diversity and composition of weaned piglets following an oral challenge with an ETEC: F4 strain and/or a treatment with colistin sulfate (CS). Twenty-eight piglets were used in this experiment and were divided into four groups: challenged untreated, challenged treated, unchallenged treated, and unchallenged untreated. Rectal swab samples were collected at five sampling times throughout the study. Total genomic DNA was used to assess the fecal microbiota diversity and composition using the V4 region of the 16S rRNA gene. The relative abundance, the composition, and the community structure of piglet fecal microbiota was highly affected by the ETEC: F4 challenge throughout the experiment, while the oral treatment with CS, a narrow spectrum antibiotic, resulted in a significant decrease of E. coli/Shigella populations during the treatment period only. This study was the first to identify some gut microbiota subgroups (e.g., Streptococcus, Lachnospiraceae) that are associated with healthy piglets as compared to ETEC: F4 challenged animals. These key findings might contribute to the development of alternative strategies to reduce the use of antimicrobials in the control of post-weaning diarrhea in pigs.

Antimicrobial resistance has become a global issue and a threat to human and animal health. Contamination of poultry carcasses with meat-borne pathogens represents both an economic and a public health concern. The use of antimicrobial processing aids (APA) during poultry processing has contributed to an improvement in the microbiological quality of poultry carcasses. However, the extensive use of these decontaminants has raised concerns about their possible role in the co-selection of antibiotic-resistant bacteria. This topic is presented in the current review to provide an update on the information related to bacterial adaptation to APA used in poultry processing establishments, and to discuss the relationship between APA bacterial adaptation and the acquisition of a new resistance phenotype to therapeutic antimicrobials by bacteria. Common mechanisms such as active efflux and changes in membrane fluidity are the most documented mechanisms responsible for bacterial cross-resistance to APA and antimicrobials. Although most studies reported a bacterial resistance to antibiotics not reaching a clinical level, the under-exposure of bacteria to APA remains a concern in the poultry industry. Further research is needed to determine if APA used during poultry processing and therapeutic antimicrobials share common sites of action in bacteria and encounter similar mechanisms of resistance.

Post-weaning diarrhea (PWD) is one of the most serious threats for the swine industry worldwide. It is commonly associated with the proliferation of enterotoxigenic Escherichia coli in the pig intestine. Colistin, a cationic antibiotic, is widely used in swine for the oral treatment of intestinal infections caused by E. coli, and particularly of PWD. However, despite the effectiveness of this antibiotic in the treatment of PWD, several studies have reported high rates of colistin resistant E. coli in swine. Furthermore, this antibiotic is considered of very high importance in humans, being used for the treatment of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). Moreover, the recent discovery of the mcr-1 gene encoding for colistin resistance in Enterobacteriaceae on a conjugative stable plasmid has raised great concern about the possible loss of colistin effectiveness for the treatment of MDR-GNB in humans. Consequently, it has been proposed that the use of colistin in animal production should be considered as a last resort treatment only. Thus, to overcome the economic losses, which would result from the restriction of use of colistin, especially for prophylactic purposes in PWD control, we believe that an understanding of the factors contributing to the development of this disease and the putting in place of practical alternative strategies for the control of PWD in swine is crucial. Such alternatives should improve animal gut health and reduce economic losses in pigs without promoting bacterial resistance. The present review begins with an overview of risk factors of PWD and an update of colistin use in PWD control worldwide in terms of quantities and microbiological outcomes. Subsequently, alternative strategies to the use of colistin for the control of this disease are described and discussed. Finally, a practical approach for the control of PWD in its various phases is proposed.

Objectives This study investigated the prevalence of Escherichia coli (E. coli) colistin resistance and mcr-1 and mcr-2 genes among extended-spectrum β-lactamase (ESBL)/AmpC-producing E. coli isolates recovered from chicken feces in Canada (Quebec), Senegal and Vietnam, and evaluated the susceptibility pattern of the colistin-resistant E. coli isolates to other clinically relevant antimicrobials. Methods A total of 327 potential ESBL/AmpC-producing E. coli isolates from chicken farms in Canada (Quebec), Senegal and Vietnam were analysed for colistin susceptibility by broth microdilution method and for the presence of mcr (1-2) genes by PCR. The pmrA and pmrB genes of colistin-resistant E. coli isolates, in the absence of mcr (1-2) genes, were sequenced. Antimicrobial resistance phenotypes of colistin-resistant E. coli isolates were determined by disk diffusion. Results None of the 108 potential ESBL/AmpC-producing E. coli isolates from seven farms in Canada were colistin-resistant or possessed mcr-1 or mcr-2 gene. A low prevalence of 2.2% of colistin resistance was observed in 93 Senegalese isolates from the 15 sampled farms, although neither mcr-1 nor mcr-2 gene was found. A prevalence of 8.7% of colistin resistance was observed among 126 Vietnamese isolates from two of the four sampled farms. The mcr-1 gene was detected in 85% of the 13 phenotypically colistin-resistant isolates. Moreover, all colistin-resistant isolates presented a multidrug-resistant phenotype. Conclusions The co-existence of the mcr-1 and ESBL/AmpC genes and the very high level of multiple drug resistance in all colistin-resistant E. coli isolates obtained from sampled chicken farms in Vietnam is a major concern.

International audience; Several experts have expressed their concerns regarding the potential increase in antimicrobial resistance (AMR) during the COVID-19 pandemic as a consequence of the increase in antimicrobial and biocide use in humans globally. However, the impact of the pandemic on antimicrobial use (AMU) and AMR in animals has yet to be discussed and evaluated. Indeed, veterinary practices have been hugely impacted by the pandemic and its restrictive measures around the world. In this perspective, we call for more research to estimate the impact of COVID-19 on AMU and AMR in both humans and animals, as well as on the environment, in coherence with the One Health approach. In addition, we argue that the current pandemic is an opportunity to accelerate the implementation of a One Health approach to tackle the AMR crisis at the global scale. Indeed, the momentum created by the increased general awareness of both the public and decision-makers for the development and maintenance of effective drugs to treat human infections, as well as for the importance of a One Health approach to prevent the emergence of infectious diseases, should be used as a lever to implement global collaborative and sustainable solutions to the complex challenges of AMR.

The safety of livestock feed is recognized worldwide as a prerequisite for the protection of animal and human health. In this context, the Canadian Food Inspection Agency is developing an Establishment-based Risk Assessment model for livestock feed mills (ERA-Feed Mill) to assist in the allocation of inspection resources based on feed safety risk. The objectives of the present study were to identify and select animal health and food safety-related risk factors along with their assessment criteria, pertaining to Canadian feed mill practices, to be included in the ERA-Feed Mill model. To do so, a review of the scientific literature and consultations with feed experts were conducted. A final list of 34 risk factors was generated, 21 identified from the scientific literature and 13 from feed expert advice. Risk factors were grouped into three clusters: inherent risk factors, mitigation factors and compliance factors for which 4, 10 and 20 factors were identified, respectively. Criteria for quantitatively assessing each risk factor were defined based on common practices found in the Canadian feed industry. These findings contributed to the initial steps of the CFIA's ERA-Feed Mill model development. By assessing the feed safety risk factors related to feed mills in Canada, this tool will help inform the CFIA on the level of oversight required to manage these risks, and will contribute to the production and maintenance of healthy livestock and the production of safe food.

The aim of the present study was to investigate the in vitro gastric stability of colistin sulfate (CS) and its antimicrobial activity against Escherichia coli and to study the impact of ETEC O149: F4 (K88) infection in pigs on CS intestinal absorption. The stability profile of CS was evaluated in a simulated gastric fluid (SGF). Antimicrobial activity of CS and its degradation products were examined in a 96-well polystyrene microplate model. The effect of experimental infection with ETEC O149: F4 on CS intestinal absorption was determined by quantification of CS systemic concentration using a validated LC–MS/MS method. A rapid degradation of CS accompanied by an increase in CS antimicrobial activity by comparison with non-degraded CS (P < 0.0001) was observed in SGF. Additionally, CS levels were not quantifiable in systemic circulation using a highly sensitive method and concurrent oral challenge did not affect CS absorption in an induction model of subclinical post-weaning diarrhea (PWD).

Background Enterotoxigenic Escherichia coli (ETEC) strains producing multiple enterotoxins are important causes of post-weaning diarrhea (PWD) in pigs. The aim of the present study was to investigate the fecal presence of ETEC enterotoxin as well as F4 and F18 genes as an indicator of colistin sulfate (CS) efficacy for treatment of PWD in pigs. Forty-eight piglets were weaned at the age of 21 days, and were divided into four groups: challenged treated, challenged untreated, unchallenged treated, and unchallenged untreated. Challenge was performed using 109 CFU of an ETEC: F4 strain, and treatment was conducted using oral CS at the dose of 50,000 IU/kg. The fecal presence of genes encoding for STa, STb, LT, F4 and F18 was detected using PCR. Results The PCR amplification of ETEC virulence genes showed that nearly 100% of pigs excreted genes encoding for STa and STb toxins in the feces before the challenge. These genes, in the absence of the gene encoding F4, were considered as a marker for F4-negative ETEC. One day after ETEC: F4 oral challenge pigs in the two challenged groups excreted the genes encoding LT and F4 in the feces. These genes were considered as a marker for F4-positive ETEC. However, the gene encoding F18 was not detected in any fecal samples of the 4 groups throughout the experiment. After only 3 days of successive oral treatment with CS, a significant reduction in both the F4-positive and negative ETEC populations was observed in the challenged treated group compared to the challenged untreated group (p

Colistin (Polymyxin E) is one of the few cationic antimicrobial peptides commercialized in both human and veterinary medicine. For several years now, colistin has been considered the last line of defense against infections caused by multidrug-resistant (MDR) Gram-negative such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Colistin has been extensively used orally since the 1960s in food animals and particularly in swine for the control of Enterobacteriaceae infections. However, with the recent discovery of plasmid-mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence of samples harboring this gene in animal isolates compared to other origins, livestock has been singled out as the principal reservoir for colistin resistance amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum- β-lactamase (ESBL) genes on a unique plasmid has been also identified in many isolates from animal origin. The use of colistin in pigs as a growth promoter and for prophylaxis purposes should be banned, and the implantation of sustainable measures in pig farms for microbial infection prevention should be actively encouraged and financed. The scientific research should be encouraged in swine medicine to generate data helping to reduce the exacerbation of colistin resistance in pigs and in manure. The establishment of guidelines ensuring a judicious therapeutic use of colistin in pigs, in countries where this drug is approved, is of crucial importance. The implementation of a microbiological withdrawal period that could reduce the potential contamination of consumers with colistin resistant bacteria of porcine origin should be encouraged. Moreover, the management of colistin resistance at the human-pig-environment interface requires the urgent use of the One Health approach for effective control and prevention. This approach needs the collaborative effort of multiple disciplines and close cooperation between physicians, veterinarians, and other scientific health and environmental professionals. This review is an update on the chemistry of colistin, its applications and antibacterial mechanism of action, and on Enterobacteriaceae resistance to colistin in pigs. We also detail and discuss the One Health approach and propose guidelines for colistin resistance management.

Colistin sulfate (CS) is used in Canada for the treatment of post weaning diarrhea (PWD), to overcome conventional therapeutic antibiotics failures. The aim of the present study was to determine the effect of a conventional oral regimen of CS for the treatment of PWD, on the development of E. coli CS resistance and to evaluate the effect of ETEC: F4 infection on CS intestinal absorption. A total of 48 pigs were used, challenge was carried out by oral administration of 10 9 CFU of a hemolytic ETEC: F4 strain resistant to nalidixic acid. CS was administered at a dose of 50.000 UI/kg twice a day for 5 days. Feces were examined clinically and bacteriologically before and after challenge to evaluate presence of diarrhea and E. coli fecal excretion. ETEC: F4 virulence factors were monitored and CS plasma concentrations were quantified by an HPLC-MS/MS. From one until six days after CS administration, a significant reduction in the fecal excretion of ETEC: F4, total E. coli, ETEC: F4 virulence factors and in diarrhea scores was observed in the challenged treated group compared to the challenged untreated group (p 0.71). A significant selection pressure on E. coli total population was observed following CS treatment (p

Colistin sulfate (CS), a polymyxin antibiotic, is used in Canada for the treatment of post-weaning diarrhea in pigs as an alternative to neomycin. The aim of the present study was to evaluate some pharmacokinetics parameters of CS and its effect on the evolution of the intestinal Escherichia coli population in pigs challenged with enterotoxigenic E. coli (ETEC): F4. A total of 14 weaned piglets were divided into two groups, a non-challenged, treated group (n=7) and a challenged, treated group (n=7). Both groups received a single oral dose of CS at 50,000 IU/Kg. Challenge was carried out by oral administration of 10 9 CFU of a hemolytic ETEC: F4 strain resistant to nalidixic acid. Blood samples were taken at 30 min and 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours post treatment from each pig and CS quantification was performed by LC-MS/MS. In the challenged group, severity of diarrhea was monitored and the presence of the ETEC:F4 strain in the feces was enumerated using 5% bovine blood agar plates containing nalidixic acid. In both groups, total E. coli counts were carried out using Petrifilm E. coli/Coliform count plates. In both groups, the plasma concentration of CS was below the lower limit of quantification (20 ng/ml). Following CS treatment, a decrease in the total E. coli and ETEC: F4 fecal counts were observed at 24 h post treatment. The fecal consistency was not affected by CS treatment. For the first time, a study of some CS pharmacokinetics parameters with a highly sensitive method showed that CS levels are not detectable in systemic circulation following oral administration, and concurrent oral challenge with an ETEC strain did not affect CS absorption. A single dose of CS resulted in reduced bacterial counts of the total E. coli and ETEC: F4 populations in the feces.

There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx), and interleukin-1 beta (IL-1β) were measured in synovial fluid. Concentrations of NOx and PGE2 in synovial fluid were lower in the test group (P0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.La vitamine E (VE) est connue par ses propriétés anti-inflammatoires et analgésiques dans le traitement de l’ostéoarthrose (OA) chez l’humain. Dans notre étude pilote nous avons utilisé un ensemble de paramètres cliniques et de laboratoire afin de déterminer si ces effets bénéfiques de la VE pourront être détectés chez le chien arthrosique, dans un modèle expérimental d’OA. Les chiens utilisés ont été divisés en 2 groupes: témoin (

Enterotoxigenic Escherichia coli (ETEC: F4) associated with post-weaning diarrhea (PWD) in pigs has developed resistance against several antimicrobial families, leading to increased use of colistin sulfate (CS) for the treatment of this disease. The objective of this study was to determine the efficacy of oral CS treatment in experimental PWD due to ETEC: F4 challenge and determine the effect of this challenge on CS intestinal absorption. In this study, 96 pigs were divided into two trials based on CS dose (100 000 or 50 000 IU/kg). Fecal shedding of ETEC: F4, total E. coli, and CS-resistant E. coli, diarrhea scores, and weight changes were evaluated. Colistin sulfate plasma concentrations were determined by HPLC–MS/MS. Regardless of the dose, CS treatment resulted in a reduction of fecal ETEC: F4 and total E. coli shedding, and in diarrhea scores but only during the treatment period. However, CS treatment resulted in a slight increase in fecal shedding of CS resistant E. coli and did not prevent weight loss in challenged pigs. In addition, challenge with ETEC: F4 resulted in an increase of CS intestinal absorption. Our study is among the first to demonstrate that under controlled conditions, CS was effective in reducing fecal shedding of ETEC: F4 and total E. coli in experimental PWD. However, CS treatment was associated with a slight selection pressure on E. coli and did not prevent pig weight loss. Further studies are needed in field conditions, to better characterize CS therapeutic regimen efficacy and bacterial resistance dissemination. Electronic supplementary material The online version of this article (doi:10.1186/s13567-016-0344-y) contains supplementary material, which is available to authorized users.