Risk factors associated with antibiotic prescriptions for cases of enteric pathogens in Canada, 2015-2019.

Inappropriate antibiotic use is a key driver of antibiotic resistance and one that can be mitigated through stewardship. A better understanding of current prescribing practices is needed to develop successful stewardship efforts. This study aims to identify factors that are associated with human cases of enteric illness receiving an antibiotic prescription. Cases of laboratory-confirmed enteric illness reported to the FoodNet Canada surveillance system between 2015 and 2019 were the subjects of this study. Laboratory data were combined with self-reported data collected from an enhanced case questionnaire that included demographic data, illness duration and symptoms, and antibiotic prescribing. The data were used to build univariable logistic regression models and a multivariable logistic regression model to explore what factors were associated with a case receiving an antibiotic prescription. The final multivariable model identified several factors as being significantly associated with cases being prescribed an antibiotic. Some of the identified associations indicate that current antibiotic prescribing practices include a substantial level of inappropriate use. This study provides evidence that antibiotic stewardship initiatives targeting infectious diarrhoea are needed to optimize antibiotic use and combat the rise of antibiotic resistance.

The National Conference on Health Disparities Student Research Forum.

The annual National Conference on Health Disparities (NCHD) was launched in 2000. It unites health professionals, researchers, community leaders, and government officials, and is a catalyzing force in developing policies, research interventions, and programs that address prevention, social determinants, health disparities, and health equity. The NCHD Student Research Forum (SRF) was established in 2011 at the Medical University of South Carolina to build high-quality biomedical research presentation capacity in primarily underrepresented undergraduate and graduate/professional students. This paper describes the unique research training and professional development aspects of the NCHD SRF. These include guidance in abstract development, a webinar on presentation techniques and methods, a vibrant student-centric conference, and professional development workshops on finding a mentor and locating scholarship/fellowship funding, networking, and strategies for handling ethical issues in research with mentors. Between 2011 and 2018, 400 undergraduate and graduate/professional students participated in the NCHD SRF. Most students were women (80.5%). Approximately half were African American or black (52.3%), 18.0% were white, and 21.3% were of Hispanic/Latinx ethnicity. The NCHD SRF is unique in several ways. First, it provides detailed instructions on developing a scientific abstract, including content area examples. Second, it establishes a mandatory pre-conference training webinar demonstrating how to prepare a scientific poster. Third, it works with the research mentors, faculty advisors, department chairs, and deans to help identify potential sources of travel funding for students with accepted abstracts. These features make the NCHD SRF different from many other conferences focused on students' scientific presentations.

A One Health Genomic Investigation of Gentamicin Resistance in Escherichia coli from Human and Chicken Sources in Canada, 2014 to 2017.

We investigated whether gentamicin resistance (Genr) in Escherichia coli isolates from human infections was related to Genr E. coli in chicken and whether resistance may be due to coselection from use of lincomycin-spectinomycin in chickens on farms. Whole-genome sequencing was performed on 483 Genr E. coli isolates isolated between 2014 and 2017. These included 205 human-source isolates collected by the Canadian Ward (CANWARD) program and 278 chicken-source isolates: 167 from live/recently slaughtered chickens (animals) and 111 from retail chicken meat collected by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). The predominant Genr gene was different in human and chicken sources; however, both sources carried aac(3)-IId, aac(3)-VIa, and aac(3)-IVa. Forty-one percent of human clinical isolates of Genr E. coli contained a blaCTX-M extended-spectrum beta-lactamase (ESBL) gene (84/205), and 53% of these were sequence type 131 (ST131). Phylogenomic analysis revealed a high diversity of Genr isolates; however, there were three small clusters of closely related isolates from human and chicken sources. Genr and spectinomycin resistance (Specr) genes were colocated in 148/167 (89%) chicken animal isolates, 94/111 (85%) chicken retail meat isolates, and 137/205 (67%) human-source isolates. Long-read sequencing of 23 isolates showed linkage of the Genr and Specr genes on the same plasmid in 14/15 (93%) isolates from chicken(s) and 6/8 (75%) isolates from humans. The use of lincomycin-spectinomycin on farms may be coselecting for gentamicin-resistant plasmids in E. coli in broiler chickens; however, Genr isolates and plasmids were mostly different in chickens and humans.

A One-Health Genomic Investigation of Gentamicin Resistance in Salmonella from Human and Chicken Sources in Canada, 2014 to 2017.

We investigated whether the increased prevalence of gentamicin resistance in Salmonella from human infections was related to a similar increased prevalence in isolates from broiler chickens and whether this increase may have been due to coselection from use of lincomycin-spectinomycin in chickens on farms. Whole-genome sequencing was performed on gentamicin-resistant (Genr) Salmonella isolates from human and chicken sources collected from 2014 to 2017 by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). We determined the genomic relatedness of strains and characterized resistance genes and plasmids. From 2014 to 2017, 247 isolates of Genr Salmonella were identified by CIPARS: 188 were from humans, and 59 were from chicken sources (26 from live animals on farm and 33 from retail meat). The five most common Genr serovars were Salmonella enterica serovars Heidelberg (n = 93; 31.5%), 4,[5],12:i:- (n = 42; 14.2%), Kentucky (n = 37; 12.5%), Infantis (n = 33; 11.2%), and Typhimurium (n = 23; 7.8%). Phylogenomic analysis revealed that for S. Heidelberg and S. Infantis, there were closely related isolates from human and chicken sources. In both sources, resistance to gentamicin and spectinomycin was most frequently conferred by aac(3)-VIa and ant(3'')-Ia, respectively. Plasmid closure confirmed linkages of gentamicin and spectinomycin resistance genes and revealed instances of similar plasmids from both sources. Gentamicin and spectinomycin resistance genes were linked on the same plasmids, and some plasmids and isolates from humans and chickens were genetically similar, suggesting that the use of lincomycin-spectinomycin in chickens may be selecting for gentamicin-resistant Salmonella in broiler chickens and that these resistant strains may be acquired by humans.

An analysis of antibiotic prescribing practices for enteric bacterial infections within FoodNet Canada sentinel sites.

OBJECTIVES: Understanding the current state of antibiotic treatment guidelines and prescribing practices for bacterial enteric infections is critical to inform antibiotic stewardship initiatives. This study aims to add to the current understanding through three objectives: (i) to identify and summarize published treatment guidelines for bacterial enteric infections; (ii) to describe observed antibiotic prescribing practices for bacterial enteric infections across three sentinel sites in Canada; and (iii) to assess concordance between observed antibiotic prescribing and treatment guidelines. METHODS: An environmental scan of treatment guidelines for bacterial enteric infections was conducted and recommendations were collated. A descriptive analysis of cases of bacterial enteric illnesses captured in FoodNet Canada's sentinel site surveillance system between 2010 and 2018 was performed. Antibiotic-use data were self-reported by cases via an enhanced questionnaire. RESULTS: Ten treatment guidelines were identified in the environmental scan. There was substantial variation between guidelines for both when to prescribe antibiotics and which antibiotics were recommended. Of the 5877 cases of laboratory-confirmed bacterial enteric illness in the three sites, 49% of cases reported having received an antibiotic prescription. Of particular significance was the finding that 21% of verotoxigenic Escherichia coli cases received a prescription. Of the 17 antibiotics recommended in the guidelines, 14 were used in practice. In addition to these, 18 other antibiotics not included in any of the guidelines reviewed were also prescribed. CONCLUSIONS: Our study suggests that a substantial proportion of enteric bacterial infections in Canada are prescribed antibiotics. These findings highlight the need to standardize treatment guidelines for enteric illnesses and could be used to inform future stewardship programme development.

Genomic Investigation of the Emergence of Invasive Multidrug-Resistant Salmonella enterica Serovar Dublin in Humans and Animals in Canada.

Salmonella enterica subsp. enterica serovar Dublin is a zoonotic pathogen that often leads to invasive bloodstream infections in humans that are multidrug resistant. Described here are the results of Canadian national surveillance of S Dublin from 2003 to 2015 in humans and bovines, principally collected through the Canadian Integrated Program for Antibiotic Resistance Surveillance (CIPARS). An increase in human infections due to multidrug-resistant (MDR) S Dublin was observed in 2010, many of which were bloodstream infections. Phylogenomic analysis of human and bovine isolates revealed a closely related network that differed by only 0 to 17 single nucleotide variants (SNVs), suggesting some potential transmission between humans and bovines. Phylogenomic comparison of global publicly available sequences of S Dublin showed that Canadian isolates clustered closely with those from the United States. A high correlation between phenotypic and genotypic antimicrobial susceptibility was observed in Canadian isolates. IS26 replication was widespread among U.S. and Canadian isolates and caused the truncation and inactivation of the resistance genes strA and blaTEM-1B A hybrid virulence and MDR plasmid (pN13-01125) isolated from a Canadian S Dublin isolate was searched against NCBI SRA data of bacteria. The pN13-01125 coding sequences were found in 13 Salmonella serovars, but S Dublin appears to be a specific reservoir. In summary, we have observed the rise of invasive MDR S Dublin in humans in Canada and found that they are closely related to bovine isolates and to American isolates in their mobile and chromosomal contents.

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

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.

Variation in outpatient oral antimicrobial use patterns among Canadian provinces, 2000 to 2010.

BACKGROUND: The volume and patterns of antimicrobial drug use are key variables to consider when developing guidelines for prescribing, and programs to address stewardship and combat the increasing prevalence of antimicrobial resistant pathogens. Because drug programs are regulated at the provincial level, there is an expectation that antibiotic use may vary among provinces. OBJECTIVE: To assess these potential differences according to province and time. METHODS: Provincial antimicrobial prescribing data at the individual drug level were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance for 2000 to 2010. Data were used to calculate two yearly metrics: prescriptions per 1000 inhabitant-days and the average defined daily doses per prescription. The proportion of liquid oral prescriptions of total prescriptions was also calculated as a proxy measure for the proportion of prescriptions given to children versus adults. To assess the significance of provincial antimicrobial use, linear mixed models were developed for each metric, accounting for repeated measurements over time. RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. Newfoundland and Labrador was found to have significantly higher prescribing rates than all other provinces (P<0.001) in 2010, as well as the mean of all other provinces (P<0.001). In contrast, Quebec exhibited significantly lower prescribing than all other provinces (P<0.001 for all provinces except British Columbia, where P=0.024) and the mean of all other provinces (P<0.001). DISCUSSION/CONCLUSION: Reports of reductions in antimicrobial use at the Canadian level are promising, especially prescribing to children; however, care must be taken to avoid the pitfall of the ecological fallacy. Reductions are not consistent among the provinces or among the classes of antimicrobial drugs dispensed in Canada.

HISTORIQUE: Le volume et les modes d'utilisation d'antimicrobiens sont des variables importantes à envisager lorsqu'on élabore des lignes directrices de prescription et des programmes pour aborder la question de la gouvernance et pour lutter contre la prévalence croissante des pathogènes résistants aux antimicrobiens. Puisque les programmes de médicaments sont réglementés sur la scène provinciale, on s'attend que l'utilisation d'antibiotiques varie entre les provinces. OBJECTIF: Évaluer ces différences potentielles selon la province et dans le temps. MÉTHODOLOGIE: Les chercheurs ont extrait les données sur la prescription de chaque médicament antimicrobien sur la scène provinciale du Programme intégré canadien de surveillance de la résistance aux antimicrobiens entre 2000 et 2010. À l'aide de ces données, ils ont calculé deux mesures annuelles : les prescriptions par 1 000 habitants-jours et les doses thérapeutiques quotidiennes moyennes dispensées par prescription. Ils ont également calculé la proportion de prescriptions orales liquides par rapport aux prescriptions totales pour établir approximativement la proportion de prescriptions administrées aux enfants par rapport aux adultes. Pour évaluer l'importance de l'utilisation d'antimicrobiens sur la scène provinciale, les chercheurs ont élaboré des modèles linéaires mixtes pour chaque mesure, tenant compte de mesures répétées dans le temps. RÉSULTATS: Les chercheurs ont constaté des différences significatives entre les provinces, ainsi que des changements importants d'utilisation dans le temps. Ils ont déterminé que Terre-Neuve-et-Labrador présentait des taux de prescription considérablement plus élevés que toutes les autres provinces (P<0,001) en 2010, ainsi que de la moyenne de toutes les autres provinces (P<0,001). Par contre, le Québec présentait des taux de prescription considérablement plus faibles que toutes les autres provinces (P<0,001 pour toutes les provinces sauf la Colombie-Britannique, où P=0,024) ainsi que de la moyenne de toutes les autres provinces (P<0,001). EXPOSÉ ET CONCLUSION: Les rapports sur la diminution de l'utilisation d'antimicrobiens sur la scène canadienne sont prometteurs, notamment les prescriptions aux enfants. Cependant, il faut s'assurer d'éviter l'écueil des erreurs écologiques. Les réductions ne sont pas uniformes entre les provinces ou entre les classes d'antimicrobiens administrées au Canada.

Longitudinal surveillance of outpatient quinolone antimicrobial use in Canada.

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is important. OBJECTIVE: To assess the use of quinolone antimicrobials within Canadian provinces over time. METHODS: ANTIMICROBIAL PRESCRIBING DATA COLLECTED BY IMS HEALTH CANADA WERE ACQUIRED FROM THE CANADIAN INTEGRATED PROGRAM FOR ANTIMICROBIAL RESISTANCE SURVEILLANCE AND THE CANADIAN COMMITTEE FOR ANTIMICROBIAL RESISTANCE, AND WERE USED TO CALCULATE TWO YEARLY METRICS: prescriptions per 1000 inhabitant-days and the mean defined daily doses (DDDs) per prescription. These measures were used to produce linear mixed models to assess differences among provinces and over time, while accounting for repeated measurements. RESULTS: The quinolone class of antimicrobials is used similarly among Canadian provinces. Year-to-year increases in quinolone prescribing occurred from 1995 to 2010, with a levelling off in the latter years. Year-to-year decreases in the DDDs per prescription were found to be significant from 2000 to 2010. DISCUSSION: Although the overall use of antimicrobials differs significantly among Canadian provinces, the use of the quinolone class does not vary at the provincial level. Results suggest that prescribing of ciprofloxacin may be a potential target for antimicrobial stewardship programs; however, decreases in the average DDDs per prescription suggest continued uptake of appropriate treatment guidelines.

INTRODUCTION: Puisque l'utilisation d'antimicrobiens s'associe souvent à l'apparition d'une résistance antimicrobienne, il est important d'en surveiller le volume et le mode d'utilisation. OBJECTIF: Évaluer l'utilisation d'antimicrobiens de la classe des quinolones au sein des provinces canadiennes au fil du temps. MÉTHODOLOGIE: Les chercheurs ont acquis les données de prescription d'antimicrobiens colligées par IMS Health Canada auprès du Programme intégré canadien de surveillance de la résistance aux antimicrobiens et du Comité canadien sur la résistance aux antibiotiques et les ont utilisées pour calculer deux mesures annuelles : les prescriptions par 1 000 habitants-jours et les doses quotidiennes définies (DTD) moyennes par prescription. Ils les ont utilisées pour produire des modèles linéaires mixtes afin d'évaluer les différences entre les provinces et au fil du temps, tout en tenant compte des mesures répétées. RÉSULTATS: Les antimicrobiens de la classe des quinolones sont utilisés de manière similaire dans les provinces canadiennes. Les prescriptions annuelles de quinolone ont augmenté de 1995 à 2010, mais ont plafonné au cours des dernières années. Les DTD par prescription ont diminué annuellement de manière significative entre 2000 et 2010. EXPOSÉ: Même si l'utilisation globale d'antimicrobiens diffère de manière significative entre les provinces canadiennes, l'utilisation de la classe des quinolones ne varie pas sur la scène provinciale. D'après les résultats, la prescription de ciprofloxacine peut être une cible potentielle des programmes de gestion des antimicrobiens. Cependant, les diminutions des DTD moyennes par prescription sont indicatrices d'une assimilation continue des directives thérapeutiques pertinentes.

Provincial and temporal variation in macrolide and lincosamide antimicrobial use by outpatients in Canada, 1995 to 2010.

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is very important. OBJECTIVE: To assess the use of macrolide and lincosamide (ML) antimicrobials within Canadian provinces over time, and to compare use rates with those reported by European countries. METHODS: ANTIMICROBIAL PRESCRIBING DATA WERE USED TO DEVELOP TWO YEARLY METRICS: prescriptions per 1000 inhabitant-days (PrIDs) and the mean defined daily doses (DDDs) per prescription, which were then used to build linear mixed models to assess differences among provinces over time. RESULTS: After accounting for repeated measures over time, prescribing rates (PrIDs) varied significantly according to province and year (P<0.001). However, little change occurred within each province over the time frame studied; from 1995 to 2010, each province had a PrID change <0.01. Quebec and British Columbia had significantly lower prescribing rates than all other provinces. No overall secular trend was apparent. In contrast, the DDDs per prescription did not vary significantly according to province, but showed a significant year-to-year increase. DISCUSSION: ML prescribing varied among provinces in Canada between 1995 and 2010, but remained relatively stable within each province. The average DDDs per ML prescription did not vary according to province, but increased linearly over time. These increases are likely to indicate that fewer prescriptions are being written for children over time, a practice supported by good antimicrobial stewardship principles.

INTRODUCTION: Puisque l'utilisation d'antimicrobiens s'associe souvent à l'apparition d'une résistance aux antimicrobiens, il est très important d'en surveiller le volume et les profils d'utilisation. OBJECTIF: Évaluer l'utilisation des antimicrobiens marcolides et lincasomides (ML) dans les provinces canadiennes au fil du temps et comparer les taux d'utilisation par rapport à ceux des pays européens. MÉTHODOLOGIE: Les données de prescription d'antimicrobiens ont permis d'établir deux mesures annuelles : les prescriptions par 1 000 habitants-jours (PrID) et les doses quotidiennes définies (DQD) moyennes par prescription, qui ont ensuite été utilisées pour créer des modèles linéaires mixtes d'évaluation des différences entre les provinces au fil du temps. RÉSULTATS: Après avoir tenu compte des mesures répétées au fil du temps, les taux de prescription (PrID) variaient de manière significative selon la province et l'année (P<0,001). Cependant, on a observé peu de changements dans chaque province pendant la période de l'étude. En effet, de 1995 à 2010, chaque province présentait un changement des PrID de moins de 0,01. Le Québec et la Colombie-Britannique présentaient un taux de prescription considérablement plus faible que toutes les autres provinces. Aucune tendance lourde globale n'était apparente. Par contre, les DQD par prescription ne variaient pas de manière significative selon la province, mais augmentait de manière significative d'une année à l'autre. EXPOSÉ: Les prescriptions de ML étaient variables entre les provinces du Canada de 1995 à 2010, mais demeuraient relativement stables dans chaque province. Les DQD moyennes par prescription de ML ne variaient pas selon la province, mais présentaient une augmentation linéaire au fil du temps. Ces augmentations sont susceptibles d'indiquer que moins de prescriptions sont rédigées pour les enfants au fil du temps, une pratique soutenue par de bons principes de gouvernance antimicrobienne.

Longitudinal surveillance of outpatient ß-lactam antimicrobial use in Canada, 1995 to 2010.

INTRODUCTION: ß-lactam antimicrobials are the most commonly prescribed group of antimicrobials in Canada, and are categorized by the WHO as critically and highly important antimicrobials for human medicine. Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is highly important. OBJECTIVE: To assess the use of penicillin and cephalosporin antimicrobials within Canadian provinces over the 1995 to 2010 time frame according to two metrics: prescriptions per 1000 inhabitant-days and the average defined daily doses dispensed per prescription. METHODS: Antimicrobial prescribing data were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and population data were obtained from Statistics Canada. The two measures developed were used to produce linear mixed models to assess differences among provinces and over time for the broad-spectrum penicillin and cephalosporin groups, while accounting for repeated measurements at the provincial level. RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. A >28% reduction in broad-spectrum penicillin prescribing occurred in each province from 1995 to 2010, and a >18% reduction in cephalosporin prescribing occurred in all provinces from 1995 to 2010, with the exception of Manitoba, where cephalosporin prescribing increased by 18%. DISCUSSION: Significant reductions in the use of these important drugs were observed across Canada from 1995 to 2010. Newfoundland and Labrador and Quebec emerged as divergent from the remaining provinces, with high and low use, respectively.

INTRODUCTION: Les ß-lactamines représentent le groupe d'antimicrobiens le plus prescrit au Canada et, d'après l'OMS, elles revêtent une importance capitale en médecine humaine. Puisque l'utilisation d'antimicrobiens s'associe souvent au développement d'une résistance antimicrobienne, il est essentiel de surveiller le volume et les modes d'utilisation de ces agents. OBJECTIF: Évaluer l'utilisation de pénicilline et de céphalosporines au sein des provinces canadiennes entre 1995 et 2010 selon deux mesures : les prescriptions par 1 000 habitants-jours et les doses théra-peutiques quotidiennes moyennes dispensées par prescription. MÉTHODOLOGIE: Les chercheurs ont extrait les données sur la prescription d'antimicrobiens du Programme intégré canadien de surveillance de la résistance aux antimicrobiens et du Comité canadien sur la résistance aux antibiotiques, et les données en population de Statistique Canada. À l'aide des deux mesures élaborées, ils ont produit des modèles linéaires mixtes pour évaluer les différences entre les provinces et dans le temps dans les groupes de pénicilline à large spectre et de céphalosporines, tout en tenant compte des mesures répétées sur la scène provinciale. RÉSULTATS: Les chercheurs ont constaté des différences significatives entre les provinces, ainsi que des changements importants d'utilisation dans le temps. Les prescriptions de pénicilline à large spectre ont diminué de plus de 28 % dans chaque province entre 1995 et 2010, et celles de céphalosporines ont reculé de plus de 18 % dans toutes les provinces entre 1995 et 2010, à l'exception du Manitoba, où les prescriptions de céphalosporines ont augmenté de 18 %. EXPOSÉ: Les chercheurs ont observé d'importantes réductions dans l'utilisation de ces médicaments au Canada entre 1995 et 2010. Terre-Neuve-et-Labrador et le Québec divergeaient des autres provinces, avec un usage élevé et faible, respectivement.

Longitudinal surveillance of outpatient tetracycline, sulfonamide-trimethoprim and 'other' antimicrobial use in Canada, 1995 to 2010.

INTRODUCTION: Monitoring the volume and patterns of use of antimicrobial agents is important in light of antimicrobial resistance. OBJECTIVE: To assess the use of three antimicrobial groups - tetracycline, sulfonamide-trimethoprim and 'other' antimicrobials - within Canadian provinces over time. METHODS: Prescription counts from 1995 to 2010 were acquired for the tetracycline and sulfonamide-trimethoprim groups of antimicrobials, and from 2001 to 2010 for the 'other' antimicrobial group. Linear mixed models were produced to assess differences among provinces and over time while accounting for repeated measurements. Prescription rate, defined daily dose per 1000 inhabitant-days and defined daily doses per prescription measures for the year 2009 were also compared with those reported by participating European Union countries to determine where Canadian provinces rank in terms of antimicrobial use among these countries. RESULTS: Prescribing of all three groups varied according to province and over time. Tetracycline and sulfonamide-trimethoprim group prescribing were significantly reduced over the study period, by 36% and 61%, respectively. Prescribing of the 'other' antimicrobial group increased in all provinces from 2001 to 2010 with the exception of Prince Edward Island, although by varying amounts (10% to 61% increases). DISCUSSION: The overall use of antimicrobials in Canada has dropped from 1995 to 2010, and the tetracycline and sulfonamide-trimethoprim groups have contributed to this decline. The use of the 'other' antimicrobials has increased, however. These results may suggest that switches are being made among these groups, particularly among the antimicrobials used to treat urinary tract infections.

INTRODUCTION: Il est important de surveiller le volume et le mode d'utilisation des antimicrobiens compte tenu de la résistance antimicrobienne. OBJECTIF: Évaluer l'utilisation de trois groupes d'antimicrobiens, soit la tétracycline, la sulfonamide-triméthoprime et d'« autres ¼ antimicrobiens dans les provinces canadiennes au fil du temps. MÉTHODOLOGIE: Les chercheurs ont obtenu le nombre de prescriptions des groupes de tétracycline et de sulfonamide-triméthoprime entre 1995 et 2010 et du groupe d'« autres ¼ antimicrobiens entre 2001 et 2010. Ils ont produit des modèles linéaires mixtes pour évaluer les différences entre les provinces et dans le temps tout en tenant compte des mesures répétées. Ils ont également comparé le taux de prescriptions, les doses quotidiennes définies par 1 000 habitants-jours et les doses quotidiennes définies par mesures de prescription à ceux des pays participants de l'Union européenne en 2009 pour déterminer le classement des provinces canadiennes en matière d'utilisation d'antimicrobiens au sein de ces pays. RÉSULTATS: Les prescriptions des trois groupes de médicaments variaient selon la province et dans le temps. La prescription des groupes de tétracycline et de sulfonamide-triméthoprime a diminué considérablement pendant la période de l'étude, soit de 36 % et de 61 %, respectivement. La prescription du groupe d'« autres ¼ antimicrobiens a augmenté dans toutes les provinces entre 2001 et 2010, à l'exception de l'Île-du-Prince-Édouard, mais selon des taux différents (augmentations de 10 % à 61 %). EXPOSÉ: L'utilisation globale d'antimicrobiens a diminué au Canada entre 1995 et 2010, et les groupes de tétracycline et de sulfonamide-triméthoprime y ont contribué. L'utilisation d'« autres ¼ antimicrobiens a toutefois augmenté. Ces résultats laissent peut-être supposer des substitutions entre ces groupes, notamment entre les antimicrobiens utilisés pour soigner les infections urinaires.

The scourge of antibiotic resistance: the important role of the environment.

Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, ß-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.

Ciprofloxacin-resistant Salmonella enterica serovar Kentucky in Canada.

We report emergence of ciprofloxacin-resistant Salmonella enterica serovar Kentucky in Canada during 2003-2009. All isolates had similar macrorestriction patterns and were multilocus sequence type ST198, which has been observed in Europe and Africa. Ciprofloxacin-resistant S. enterica serovar Kentucky represents 66% of all ciprofloxacin-resistant nontyphoidal Salmonella sp. isolates observed in Canada since 2003.

Emergence of multidrug-resistant Salmonella enterica serotype 4,[5],12:i:- involving human cases in Canada: results from the Canadian Integrated Program on Antimicrobial Resistance Surveillance (CIPARS), 2003-10.

OBJECTIVES: Over the last decade, a marked increase in Salmonella enterica serotype 4,[5],12:i:- with a core resistance to ampicillin, streptomycin, sulphonamides and tetracycline (ASSuT) has been observed in Europe. This study describes the emergence and characterization of isolates of multidrug-resistant Salmonella 4,[5],12:i:- in Canada. METHODS: Human clinical isolates of Salmonella 4,[5],12:i:- were identified by provincial laboratories from 2003 to 2010. Serotyping and phage typing were performed by standardized methodologies. MIC values were determined using broth microdilution. PCR was used to determine the presence of resistance genes. Multilocus sequence typing was performed on a selected number of isolates. RESULTS: A total of 26 251 Salmonella were submitted as part of the Canadian Integrated Program on Antibiotic Resistance Surveillance (CIPARS). Of these, Salmonella 4,[5],12:i:- accounted for a total of 766 isolates (2.9%), and the number increased significantly from 42 (1.4%) in 2003 to 164 (4.8%) in 2010. The ASSuT+ phenotype was observed in 11.9% (n = 91) of Salmonella 4,[5],12:i:- isolates and increased from two isolates in 2003 to 35 isolates in 2010. Two sequence types (STs) were observed. ST34 was mainly associated with the ASSuT isolates (n = 24; 38%), which contained blaTEM, strA-strB, tet(B) and sul2. ST19 was more likely to be associated with the ACSSuT phenotype and contained blaTEM, floR, strA-strB, sul2 and tet(A) or blaPSE-1, floR, aadA2, sul1 and tet(G). CONCLUSIONS: The prevalence of Salmonella 4,[5],12:i:- has significantly increased from 2003 to 2010 and it is now the fifth most common serotype reported in Canada causing human disease. Similar antimicrobial resistance patterns, phage types and STs have been observed in Europe.

Comparison of antimicrobial resistance patterns of Salmonella spp. and Escherichia coli recovered from pet dogs from volunteer households in Ontario (2005-06).

OBJECTIVES: To compare the antimicrobial resistance (AMR) patterns of Salmonella spp. and Escherichia coli in the faeces of pet dogs from volunteer households in Southwestern Ontario, Canada. METHODS: From October 2005 to May 2006, 138 dogs from 84 Ontario households were recruited to participate in a cross-sectional study. Five consecutive daily faecal samples were collected from each dog and cultured for Salmonella spp. and E. coli. A panel of 15 antimicrobials from seven antimicrobial classes was used for susceptibility testing. RESULTS: E. coli and Salmonella spp. were recovered from 96.4% and 23.2% of dogs, respectively. In total, 515 bacterial isolates from 136 dogs from 83 households were sent for antimicrobial susceptibility testing with 80.4% of isolates being pan-susceptible. The most common resistance pattern was to amoxicillin/clavulanic acid, ampicillin, cefoxitin, ceftiofur and ceftriaxone, present in 13.3% of Salmonella isolates and 1.3% of E. coli isolates. Fifty-eight of the isolates were resistant to two or more drug classes, with 70.7% and 29.3% being E. coli and Salmonella, respectively. Based on multilevel logistic regression, the odds of resistance were greater in E. coli than Salmonella [odds ratio = 3.2; 95% confidence interval (CI) = 1.22-8.43]. Agreement in resistance between E. coli and Salmonella isolates from the same dog was low [prevalence-adjusted, bias-adjusted kappa (PABAK) = 0.38; 95% CI = 0.30-0.46]. CONCLUSIONS: Pet dogs are a potential household source of antimicrobial-resistant Salmonella spp. and E. coli. However, extrapolating the epidemiology of antimicrobial resistance in pathogens, like Salmonella, from E. coli should be done with caution.

Measures used to assess the burden of ESBL-producing Escherichia coli infections in humans: a scoping review.

BACKGROUND: ESBL-producing bacteria pose a serious challenge to both clinical care and public health. There is no standard measure of the burden of illness (BOI) of ESBL-producing Escherichia coli (ESBL-EC) in the published literature, indicating a need to synthesize available BOI data to provide an overall understanding of the impact of ESBL-EC infections on human health. OBJECTIVES: To summarize the characteristics of BOI reporting in the ESBL-EC literature to (i) describe how BOI associated with antimicrobial resistance (AMR) is measured and reported; (ii) summarize differences in other aspects of reporting between studies; and (iii) highlight the common themes in research objectives and their relation to ESBL-EC BOI. METHODS AND RESULTS: Two literature searches, run in 2013 and 2018, were conducted to capture published studies evaluating the BOI associated with ESBL-EC infections in humans. These searches identified 1723 potentially relevant titles and abstracts. After relevance screening of titles and abstracts and review of full texts, 27 studies were included for qualitative data synthesis. This review identified variability in the reporting and use of BOI measures, study characteristics, definitions and laboratory methods for identifying ESBL-EC infections. CONCLUSIONS: Decision makers often require BOI data to make science-based decisions for the implementation of surveillance activities or risk reduction policies. Similarly, AMR BOI measures are important components of risk analyses and economic evaluations of AMR. This review highlights many limitations to current ESBL-EC BOI reporting, which, if improved upon, will ensure data accessibility and usefulness for ESBL-EC BOI researchers, decision makers and clinicians.