Whole-genome sequencing (WGS) will soon replace traditional phenotypic methods for routine testing of foodborne antimicrobial resistance (AMR). WGS is expected to improve AMR surveillance by providing a greater understanding of the transmission of resistant bacteria and AMR genes throughout the food chain, and therefore support risk assessment activities. At this stage, it is unclear how WGS data can be integrated into quantitative microbial risk assessment (QMRA) models and whether their integration will impact final risk estimates or the assessment of risk mitigation measures. This review explores opportunities and challenges of integrating WGS data into QMRA models that follow the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR. We describe how WGS offers an opportunity to enhance the next-generation of foodborne AMR QMRA modeling. Instead of considering all hazard strains as equally likely to cause disease, WGS data can improve hazard identification by focusing on those strains of highest public health relevance. WGS results can be used to stratify hazards into strains with similar genetic profiles that are expected to behave similarly, e.g., in terms of growth, survival, virulence or response to antimicrobial treatment. The QMRA input distributions can be tailored to each strain accordingly, making it possible to capture the variability in the strains of interest while decreasing the uncertainty in the model. WGS also allows for a more meaningful approach to explore genetic similarity among bacterial populations found at successive stages of the food chain, improving the estimation of the probability and magnitude of exposure to AMR hazards at point of consumption. WGS therefore has the potential to substantially improve the utility of foodborne AMR QMRA models. However, some degree of uncertainty remains in relation to the thresholds of genetic similarity to be used, as well as the degree of correlation between genotypic and phenotypic profiles. The latter could be improved using a functional approach based on prediction of microbial behavior from a combination of ‘omics’ techniques (e.g., transcriptomics, proteomics and metabolomics). We strongly recommend that methodologies to incorporate WGS data in risk assessment be included in any future revision of the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR.
There is a paucity of data on the reason for and the quantity of antimicrobials used in broiler chickens in Canada. To address this, the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) implemented surveillance of antimicrobial use (AMU) and antimicrobial resistance (AMR) in broiler chicken flocks in 2013. Shortly after this (2014), the poultry industry banned the preventive use of ceftiofur in broiler chickens. The objectives of this analysis were to describe antimicrobial use (AMU) in Canadian broiler chickens between 2013 and 2015 (n = 378 flocks), compare these results to other animal species in Canada, to highlight the utility of farm surveillance data to evaluate the impact of a policy change, and to explore how different antimicrobial use metrics might affect data interpretation and communication. The surveillance data indicated that the poultry industry policy resulted in lower antimicrobial use and resistance, and they successfully captured information on when, where, why, and how much antimicrobials were being used. The majority of antimicrobials were administered via the feed (95%). The relative frequency of antimicrobial classes used in broiler chickens differed from those used in swine or in food animal production in general. Coccidiostats were the most frequently used antimicrobial classes (53% of total kg). Excluding coccidiostats, the top three most frequently used antimicrobial classes were bacitracin (53% of flocks), virginiamycin (25%) and avilamycin (21%), mainly used for the prevention of necrotic enteritis. Depending on the AMU metric utilized, the relative rankings of the top antimicrobials changed; hence the choice of the AMU metric is an important consideration for any AMU reporting. When using milligrams/Population Correction Unit (mg/PCU) the top three antimicrobial classes used were bacitracins (76 mg/PCU), trimethoprim-sulfonamides (24 mg/PCU), and penicillins (15 mg/PCU), whereas when using a number of Defined Daily Doses in animals using Canadian standards /1,000 chicken-days at risk (nDDDvetCA/1,000 CD) the ranking was bacitracins (223 nDDDvetCA/1,000 CD), streptogramins (118 nDDDvetCA/1,000 CD), and trimethoprim-sulfonamides (87 nDDDvetCA/1,000 CD). The median animal treatment days in feed for one cycle (ATD/cycle) during the three-year study were 34 ATD/cycle; this was equal to the mean age of the flocks at pre-harvest sampling day (days at risk), indicating that the studied flocks except those that were raised without antibiotics and organic, were fed with medicated rations throughout the observation period. Overall, more than half (59%) of antimicrobials used in broiler chickens were in classes not used in human medicine, such as ionophores and chemical coccidiostats aimed to prevent coccidiosis. Compared to grower-finisher pigs and in production animal species (national sales data), the mg/PCU of antimicrobials used in broiler chickens was relatively lower. The findings of this paper highlighted the importance of farm-level AMU surveillance in mea...
Using data from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), we aimed to describe trends in antimicrobial use (AMU) in broiler chickens and turkeys, to compare AMU across species, to compare with trends in antimicrobial resistance (AMR), and to assess the effects of various AMU/AMR units of measurement (metrics and indicators) on data integration. Data on AMU and AMR in enteric bacteria, collected from 2013 to 2017 from broiler chickens ( n = 143 flocks) and turkeys ( n = 145) were used. In broiler chickens, the total AMU in milligrams/population correction unit (mg/PCU Br ) decreased by 6%, the number ( n ) of defined daily doses for animals using Canadian standards (nDDDvetCA) per 1,000 broiler chicken-days decreased by 12%, and nDDDvetCA/PCU decreased by 6%. In turkeys, the mg/PCU Tk decreased by 1%, whereas the nDDDvetCA/1,000 turkey-days and the nDDDvetCA/PCU increased by 1 and 5%, respectively. The types of antimicrobial classes used in both species were similar. Using the frequency of flocks reporting use (i.e., number of flocks reporting use/number of flocks participating) as a measurement, the use of certain antimicrobials changed over time (e.g., Broilers, decreased cephalosporin use, virginiamycin use, emerging use of lincomycin-spectinomycin, and avilamycin; Turkeys: increased trimethoprim-sulfonamides and macrolide use). The trends in resistance to specific antimicrobials paralleled the frequency and quantity of use (e.g., ceftriaxone use decreased—ceftriaxone resistance decreased, and gentamicin use increased—gentamicin resistance increased) in some situations, but not others (decreased fluoroquinolone use—increased ciprofloxacin resistance). AMR data were summarized using the AMR indicator index (AMR Ix). The most notable AMR Ix trend was the decrease in ceftriaxone AMR Ix among Escherichia coli (0.19 to 0.07); indicative of the success of the poultry industry action to eliminate the preventive use of third generation cephalosporins. Other trends observed were the increase in ciprofloxacin AMR Ix among Campylobacte r from 0.23 to 0.41 and gentamicin AMR Ix among E. coli from 0.11 to 0.22, suggestive of the persistence/emergence of resistance related to previous and current AMU not captured in our surveillance timeframe. These data highlight the necessity of multiple AMU and AMR indicators for monitoring the impact of stewardship activities and interventions.
This study characterized cefoxitin-resistant and -susceptible Salmonella enterica serovar Heidelberg strains from humans, abattoir poultry, and retail poultry to assess the molecular relationships of isolates from these sources in Québec in 2012. Isolates were collected as part of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). All isolates were subjected to antimicrobial susceptibility testing, PCR for CMY-2, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS). A total of 113 S. Heidelberg isolates from humans (n = 51), abattoir poultry (n = 18), and retail poultry (n = 44) were studied. All cefoxitin-resistant isolates (n = 65) were also resistant to amoxicillin-clavulanic acid, ampicillin, ceftiofur, and ceftriaxone, and all contained the CMY-2 gene. PFGE analysis showed that 111/113 (98.2%) isolates clustered together with ≥90% similarity. Core genome analysis using WGS identified 13 small clusters of isolates with 0 to 4 single nucleotide variations (SNVs), consisting of cefoxitin-resistant and -susceptible human, abattoir poultry, and retail poultry isolates. CMY-2 plasmids from cefoxitin-resistant isolates all belonged to incompatibility group I1. Analysis of IncI1 plasmid sequences revealed high identity (95 to 99%) to a previously described plasmid (pCVM29188_101) found in Salmonella Kentucky. When compared to pCVM29188_101, all sequenced cefoxitin-resistant isolates were found to carry 1 of 10 possible variant plasmids. Transmission of S. Heidelberg may be occurring between human, abattoir poultry, and retail poultry sources, and transmission of a common CMY-2 plasmid may be occurring among S. Heidelberg strains with variable genetic backgrounds.
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