Carolee Carson

Ciprofloxacin-Resistant Campylobacter spp. in Retail Chicken, Western Canada

During 2005–2010, the Canadian Integrated Program for Antimicrobial Resistance Surveillance identified increased prevalence of ciprofloxacin (a fluororquinolone) resistance among Campylobacter isolates from retail chicken in British Columbia (4%–17%) and Saskatchewan (6%–11%), Canada. Fluoroquinolones are critically important to human medicine and are not labeled for use in poultry in Canada.

An Assessment of Antimicrobial Resistant Disease Threats in Canada

Background Antimicrobial resistance (AMR) of infectious agents is a growing concern for public health organizations. Given the complexity of this issue and how widespread the problem has become, resources are often insufficient to address all concerns, thus prioritization of AMR pathogens is essential for the optimal allocation of risk management attention. Since the epidemiology of AMR pathogens differs between countries, country-specific assessments are important for the determination of national priorities. Objective To develop a systematic and transparent approach to AMR risk prioritization in Canada. Methods Relevant AMR pathogens in Canada were selected through a transparent multi-step consensus process (n=32). Each pathogen was assessed using ten criteria: incidence, mortality, case-fatality, communicability, treatability, clinical impact, public/political attention, ten-year projection of incidence, economic impact, and preventability. For each pathogen, each criterion was assigned a numerical score of 0, 1, or 2, and multiplied by criteria-specific weighting determined through researcher consensus of importance. The scores for each AMR pathogen were summed and ranked by total score, where a higher score indicated greater importance. A sensitivity analysis was conducted to determine the effects of changing the criteria-specific weights. Results The AMR pathogen with the highest total weighted score was extended spectrum B-lactamase-producing (ESBL) Enterobacteriaceae (score=77). When grouped by percentile, ESBL Enterobacteriaceae, Clostridium difficile, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus were in the 80-100th percentile. Conclusion This assessment provides useful information for prioritising public health strategies regarding AMR resistance at the national level in Canada. As the AMR environment and challenges change over time and space, this systematic and transparent approach can be adapted for use by other stakeholders domestically and internationally. Given the complexity of influences, resource availability and multiple stakeholders, regular consideration of AMR activities in the public health realm is essential for appropriate and responsible prioritisation of risk management that optimises the health and security of the population.

A Whole-Genome Sequencing Approach To Study Cefoxitin-Resistant Salmonella enterica Serovar Heidelberg Isolates from Various Sources

ABSTRACT 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.

Estimating the Number of Human Cases of Ceftiofur-Resistant Salmonella enterica serovar Heidelberg in Québec and Ontario, Canada

A stochastic model was used to estimate the number of human cases of ceftiofur-resistant Salmonella enterica serovar Heidelberg in Québec and Ontario attributable to chicken consumption and excess cases attributable to human prior antimicrobial consumption. The annual mean incidence of S. Heidelberg (Québec/Ontario) decreased from 70/62 cases per 100 000 in 2004 to 29/30 cases per 100 000 in 2007 (Québec)/2008 (Ontario), increasing to 59/45 cases per 100 000 in 2011. The annual mean incidence of ceftiofur-resistant cases from chicken decreased from 8/7 cases per 100 000 in 2004 to 1/1 cases per 100 000 in 2007 (Québec)/2008 (Ontario), increasing to 7/5 cases per 100 000 in 2011. The annual mean total number of excess ceftiofur-resistant cases from chicken attributable to human prior antimicrobial consumption (Québec/Ontario) decreased from 71/123 in 2004 to 6/24 in 2007 (Québec)/2008 (Ontario), but increased to 62/91 in 2011. This model will support future work to determine the increased severity, mortality and healthcare costs for ceftiofur-resistant Salmonella Heidelberg infections. These results provide a basis for the evaluation of future public health interventions to address antimicrobial resistance.

Antimicrobial use surveillance in broiler chicken flocks in Canada, 2013-2015

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 measuring the impact of interventions to reduce antimicrobials in poultry.

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.

A comparison of modelling options to assess annual variation in susceptibility of generic Escherichia coli isolates to ceftiofur, ampicillin and nalidixic acid from retail chicken meat in Canada

Statistical modelling of antimicrobial resistance (AMR) data is an important aspect of AMR surveillance programs; however, minimum inhibitory concentration (MIC) data can be challenging to model. The conventional approach is to dichotomize data using established breakpoints, then use logistic regression modelling for analysis. A disadvantage of this approach is a loss of information created by dichotomizing the data. The objectives of the study were to compare the performance and results of different regression models for the analysis of annual variation in susceptibility of generic Escherichia coli (E. coli) isolates to ceftiofur, ampicillin and nalidixic acid from retail chicken meat surveillance samples. E. coli susceptibility data for the three antimicrobials from retail chicken samples from 2007 to 2014 were obtained from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). Annual variation in susceptibility for each antimicrobial was evaluated using multivariable linear, tobit, logistic, multinomial, ordinal and complementary log-log regression models (clog-log). MIC (log2), censored MIC (log2), resistant/susceptible, and categorized MIC (3 or 4 categories) data were used as outcome variables for the appropriate statistical models. Year and region were modelled as categorical predictor variables. Random intercepts were included in the ceftiofur and ampicillin models to account for clustering by retail establishment. The model assumptions evaluated for the mixed models included homoscedasticity and normality of residuals (linear and tobit), homoscedasticity and normality of best linear unbiased predictions (all models), proportional odds (ordinal), and proportional hazards (clog-log). Fixed effects models were used for the nalidixic acid models. The model assumptions evaluated for the fixed effects models included homoscedasticity and normality of residuals (linear and tobit), goodness-of-fit test (logistic and multinomial), proportional odds (ordinal), and proportional hazards (clog-log).Only logistic and multinomial models met model assumptions. Significant annual variation in susceptibility to all three antimicrobials was identified by the multinomial regression models, whereas the logistic regression models only identified significant annual variation in susceptibility to ceftiofur. The multinomial regression model consistently identified additional significant annual variation in susceptibility compared to the logistic regression model. The multinomial modelling approach was able to identify differences between MIC categories within susceptible MIC values, which were below the breakpoint (R) detection level. Given the convention of dichotomizing susceptibility data, the logistic regression approach is likely to remain the standard method of analysis for AMR surveillance data; however, the results of this study demonstrate that multinomial regression should be considered for the analysis of AMR surveillance data.

Comparison of annual and regional variation in multidrug resistance using various classification metrics for generic Escherichia coli isolated from chicken abattoir surveillance samples in Canada

Antimicrobial resistance (AMR) and related multidrug resistance (MDR) are important global public health issues. The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) conducts surveillance of AMR in enteric bacteria and monitors MDR. However, the analysis of MDR is complicated by the lack of consensus for MDR definitions. The objectives were to describe the most common resistance patterns in generic E. coli isolates from chicken cecal samples and determine the impact of using different MDR metrics for analysis of annual and regional variation in MDR. From 2006 to 2015, 1598 E. coli isolates were collected from chickens at slaughter for CIPARS. Three MDR classification metrics were used: MDR-drug (MDR if the isolate was resistant (R) to ≥3 of the 13 antimicrobials); MDR-cat (MDR if R to ≥3 of the 9 antimicrobials categories); and MDR-class (MDR if R to ≥3 of the 6 antimicrobial classes). The most frequent resistance patterns overall, and by year and region were extracted along with patterns that included resistance to quinolones, and third generation cephalosporins and/or β-lactams with β-lactamase inhibitors. For each MDR metric, mixed logistic regression models, which included random intercepts for abattoir, were fitted to analyze the association between prevalence of MDR, and year and region. Interaction effects between year and region were evaluated. Overall, and in all years and regions, non-resistant was the most common resistance pattern (24.9%, 95% CI 22.8-27.1%). Resistance patterns that included third generation cephalosporins and β-lactams with β-lactamase inhibitors were common. The prevalence of MDR was variable: MDR-class 38.5% (95% CI 36.1-41.0%); MDR-cat 49.4% (95% CI 46.9-51.9%); and MDR-drug 53.3% (95% CI 50.8-55.8%). Based on models fitted with individual fixed effects, significant annual variation in the prevalence of MDR was identified with MDR-drug and MDR-class models. Significant regional variation was identified for all three MDR metric models. Significant interaction effects between year and region were identified with the MDR-drug and MDR-cat multivariable mixed logistic regression models. The interpretation of the association between the prevalence of MDR, and year and region differed depending on the MDR metric used. These results are supportive of the previous concerns that caution must be taken when comparing MDR results between studies. Global consensus is needed for the optimal MDR classification metric for foodborne enteric bacteria AMR surveillance.

Identifying non-traditional stakeholders with whom to engage, when mitigating antimicrobial resistance in foodborne pathogens (Canada)

ObjectiveAntimicrobial resistance (AMR) is a critical public health issue that involves interrelationships between people, animals, and the environment. Traditionally, interdisciplinary efforts to mitigate AMR in the food chain have involved public health, human and veterinary medicine, and agriculture stakeholders. Our objective was to identify a more diverse range of stakeholders, beyond those traditionally engaged in AMR mitigation efforts, via diagramming both proximal and distal factors impacting, or impacted by, use and resistance along the Canadian food chain.ResultsWe identified multiple stakeholders that are not traditionally engaged by public health when working to mitigate AMR in the food chain, including those working broadly in the area of food (e.g., nutrition, food security, international market economists) and health (e.g., health communication, program evaluation), as well as in domains as diverse as law, politics, demography, education, and social innovation. These findings can help researchers and policymakers who work on issues related to AMR in the food chain to move beyond engaging the ‘traditional’ agri-food stakeholders (e.g., veterinarians, farmers), to also engage those from the wider domains identified here, as potential stakeholders in their AMR mitigation efforts.