A scoping review of factors associated with antimicrobial-resistant Campylobacter species infections in humans.

Human infection with antimicrobial-resistant Campylobacter species is an important public health concern due to the potentially increased severity of illness and risk of death. Our objective was to synthesise the knowledge of factors associated with human infections with antimicrobial-resistant strains of Campylobacter. This scoping review followed systematic methods, including a protocol developed a priori. Comprehensive literature searches were developed in consultation with a research librarian and performed in five primary and three grey literature databases. Criteria for inclusion were analytical and English-language publications investigating human infections with an antimicrobial-resistant (macrolides, tetracyclines, fluoroquinolones, and/or quinolones) Campylobacter that reported factors potentially linked with the infection. The primary and secondary screening were completed by two independent reviewers using Distiller SR®. The search identified 8,527 unique articles and included 27 articles in the review. Factors were broadly categorised into animal contact, prior antimicrobial use, participant characteristics, food consumption and handling, travel, underlying health conditions, and water consumption/exposure. Important factors linked to an increased risk of infection with a fluoroquinolone-resistant strain included foreign travel and prior antimicrobial use. Identifying consistent risk factors was challenging due to the heterogeneity of results, inconsistent analysis, and the lack of data in low- and middle-income countries, highlighting the need for future research.

A scoping review of factors potentially linked with antimicrobial-resistant bacteria from turkeys (iAM.AMR Project).

Antimicrobial resistance (AMR) is a complex problem that is a threat to global public health. Consumption of turkey meat may be an important source of foodborne exposure to resistant bacteria; recent outbreaks of multi-drug-resistant Salmonella Reading in Canada and the USA have implicated raw turkey products. To better understand the epidemiology of AMR in farmed turkey production, a scoping review was conducted. The objectives were to identify (1) modifiable factors potentially associated with antimicrobial-resistant Campylobacter, Enterococcus, Escherichia coli and Salmonella enterica along the farm-to-fork pathway in turkeys, and (2) data gaps with respect to factors potentially associated with AMR and Canadian commercial turkey production. A comprehensive search of the peer-reviewed literature was conducted in 2019 and updated in 2021. Thirteen references were included, reporting 36 factors. Antimicrobial use factors and their potential associations with AMR were most frequently reported (n = 15 factors; 42%), followed by biosecurity (n = 11; 31%) and management practices (n = 10; 28%). This review revealed important data gaps; no factors pertaining to S. enterica or to stages other than the farm (e.g. abattoir, retail) were identified, and only one Canadian reference was identified. These findings will inform priorities for future research and surveillance regarding turkeys and AMR.

Ceftiofur-resistant Salmonella enterica serovar Heidelberg of poultry origin - a risk profile using the Codex framework.

Codex published the 'Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance' to standardise the approach for evaluating risk posed by foodborne antimicrobial-resistant bacteria. One of the first steps in the guidelines is to compile a risk profile, which provides the current state of knowledge regarding a food safety issue, describes risk management options and recommends next steps. In Canada, ceftiofur/ceftriaxone-resistant Salmonella enterica subsp. enterica serovar Heidelberg from poultry was identified as an antimicrobial resistance (AMR) food safety issue. The first objective of this article was to contextualise this food safety issue, using the risk profile format of the Codex Guidelines. A second objective was to evaluate the applicability of the Codex Guidelines. This risk profile indicated that ceftiofur/ceftriaxone-resistant S. Heidelberg (CSH) was commonly isolated from poultry and was associated with severe disease in humans. Ceftiofur use in poultry hatcheries temporally mirrored the prevalence of CSH from poultry meat at retail and from people with salmonellosis. The evidence was sufficient to indicate the need for risk management options, such as restricting the use of ceftiofur in poultry. The Codex Guidelines provided a useful approach to summarise data for decision-makers to evaluate an AMR food safety issue.

A farm-to-fork quantitative risk assessment model for Salmonella Heidelberg resistant to third-generation cephalosporins in broiler chickens in Canada.

Salmonella Heidelberg resistant to ceftiofur (a third-generation cephalosporin antimicrobial agent) in broiler chicken products pose a risk to public health in Canada. The objective of this study was to assess the extent of that risk and to evaluate the effect of intervention measures along the agri-food chain. A stochastic farm-to-fork quantitative microbial risk assessment model was developed following the Codex Alimentarius Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance. Different scenarios were analyzed to assess the individual relative effects of 18 possible interventions in comparison to a baseline scenario. The baseline scenario represented the first year of on-farm antimicrobial use surveillance in the Canadian broiler industry and the year before an industry-imposed ban on the preventive use of antimicrobials of very high importance to human health (2013), where 31.3% of broiler flocks consisted of birds to which ceftiofur was administered. The baseline scenario predicted an average probability of illness of 1.1 per 100,000 servings (SE: 0.064 per 100,000), corresponding to an average of 22,000 human infections (SE: 1900) with ceftiofur-resistant S. Heidelberg per year, which is likely an overestimation. This risk was reduced by 90% or 20% when two separate scenarios designed to capture the effect of withdrawing preventive ceftiofur use from poultry production were simulated using different approaches; data used for the former scenario were confounded by other potential concomitant control measures (e.g. Salmonella vaccination programme), so the true effect likely lies somewhere between the two estimates. A theoretical 'worst case' scenario where all flocks had birds exposed to ceftiofur increased the risk by 107%. A 50% reduction in the probability of human prior exposure to antimicrobials, which has a selective and competitive effect for Salmonella spp. following ingestion of contaminated products, reduced the risk by 65%. Other promising measures that could be considered for further risk management included improved cleaning and disinfection between broiler flocks on farm (risk reduction by 26%), exclusive use of air chilling (risk reduction by 34%), and the improvement of meat storage and preparation conditions, e.g., no temperature abuse at retail (risk reduction by 88%). These findings showed the importance of a structured approach to assessing and potentially implementing effective interventions to reduce the risk associated with ceftiofur-resistant S. Heidelberg at different steps along the agri-food chain. Major data gaps included information on concentrations of resistant bacteria, cross contamination at processing and how ceftiofur-resistant S. Heidelberg behave in comparison with susceptible ones, e.g., in terms of growth and survival ability, as well as pathogenicity and virulence.

A within-flock model of Salmonella Heidelberg transmission in broiler chickens.

As part of the development of a quantitative microbial risk assessment (QMRA) model of third-generation cephalosporins (3GC)-resistant Salmonella Heidelberg, a compartmental (SEIR) model for S. Heidelberg transmission within a typical Canadian commercial broiler chicken flock was developed. The model was constructed to estimate the within-flock prevalence and the bacterial concentration in the barn environment at pre-harvest, and to assess the effect of selected control measures. The baseline scenario predicted an average within-flock prevalence of 23.5 % (95 % tolerance interval: 15.7-31.4) and an average bacterial concentration of 3.579 (0-4.294) log CFU/g of feces in the barn environment at pre-harvest (on the day the flock is sent to slaughter). Because vertical introduction of S. Heidelberg into the barn was already uncommon in the baseline scenario, vaccination of broiler parent flocks appeared to have a negligible effect, while vaccination of broiler chicken flocks substantially reduced the bacterial concentration at pre-harvest. Cleaning and disinfection between batches markedly reduced the within-flock prevalence at pre-harvest, but the effect on bacterial concentration was limited outside of the beginning of the production period. Extending downtime between batches by 7 days had little effect on within-flock prevalence or bacterial concentration of S. Heidelberg when compared to the baseline scenario. This study provides a basis to describe S. Heidelberg dynamics within a broiler chicken flock and to predict the within-flock prevalence and bacterial concentration at pre-harvest, and includes a description of the limitations and data gaps. The results of these analyses and associated uncertainties are critical information for populating QMRA models of the downstream impacts on public health from on-farm and other food-chain practices. Specifically, the study findings will be integrated into a broader farm-to-fork QMRA model to support the risk-based control of S. Heidelberg resistant to 3GC in broiler chicken in Canada.

Integrating Whole-Genome Sequencing Data Into Quantitative Risk Assessment of Foodborne Antimicrobial Resistance: A Review of Opportunities and Challenges.

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.

Factors potentially linked with the occurrence of antimicrobial resistance in selected bacteria from cattle, chickens and pigs: A scoping review of publications for use in modelling of antimicrobial resistance (IAM.AMR Project).

Antimicrobial resistance is a complex issue with a large volume of published literature, and there is a need for synthesis of primary studies for an integrated understanding of this topic. Our research team aimed to have a more complete understanding of antimicrobial resistance in Canada (IAM.AMR Project) using multiple methods including the literature reviews and quantitative modelling. To accomplish this goal, qualitative features of publications (e.g., geographical location, study population) describing potential relationships between the occurrence of antimicrobial resistance and factors (e.g., antimicrobial use; management system) were of particular interest. The objectives of this review were to (a) describe the available peer-reviewed literature reporting potential relationships between factors and antimicrobial resistance; and (b) to highlight data gaps. A comprehensive literature search and screening were performed to identify studies investigating factors potentially linked with antimicrobial resistance in Campylobacter species, Escherichia coli and Salmonella enterica along the farm-to-fork pathway (farm, abattoir (slaughter houses) and retail meats) for the major Canadian livestock species (beef cattle, broiler chicken and pigs). The literature search returned 14,966 potentially relevant titles and abstracts. Following screening of titles, abstracts and full-text articles, the qualitative features of retained studies (n = 28) were extracted. The most common factors identified were antimicrobial use (n = 13 studies) and type of farm management system (e.g., antibiotic-free, organic; n = 8). Most studies were conducted outside of Canada and involved investigations at the farm level. Identified data gaps included the effect of vaccination, industry-specific factors (e.g., livestock density) and factors at sites other than farm along the agri-food chain. Further investigation of these factors and other relevant industry activities are needed for the development of quantitative models that aim to identify effective interventions to mitigate the occurrence of antimicrobial resistance along the agri-food chain.