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.

How to measure the impacts of antibiotic resistance and antibiotic development on empiric therapy: new composite indices.

OBJECTIVES: We aimed to construct widely useable summary measures of the net impact of antibiotic resistance on empiric therapy. Summary measures are needed to communicate the importance of resistance, plan and evaluate interventions, and direct policy and investment. DESIGN, SETTING AND PARTICIPANTS: As an example, we retrospectively summarised the 2011 cumulative antibiogram from a Toronto academic intensive care unit. OUTCOME MEASURES: We developed two complementary indices to summarise the clinical impact of antibiotic resistance and drug availability on empiric therapy. The Empiric Coverage Index (ECI) measures susceptibility of common bacterial infections to available empiric antibiotics as a percentage. The Empiric Options Index (EOI) varies from 0 to 'the number of treatment options available', and measures the empiric value of the current stock of antibiotics as a depletable resource. The indices account for drug availability and the relative clinical importance of pathogens. We demonstrate meaning and use by examining the potential impact of new drugs and threatening bacterial strains. CONCLUSIONS: In our intensive care unit coverage of device-associated infections measured by the ECI remains high (98%), but 37-44% of treatment potential measured by the EOI has been lost. Without reserved drugs, the ECI is 86-88%. New cephalosporin/ß-lactamase inhibitor combinations could increase the EOI, but no single drug can compensate for losses. Increasing methicillin-resistant Staphylococcus aureus (MRSA) prevalence would have little overall impact (ECI=98%, EOI=4.8-5.2) because many Gram-positives are already resistant to ß-lactams. Aminoglycoside resistance, however, could have substantial clinical impact because they are among the few drugs that provide coverage of Gram-negative infections (ECI=97%, EOI=3.8-4.5). Our proposed indices summarise the local impact of antibiotic resistance on empiric coverage (ECI) and available empiric treatment options (EOI) using readily available data. Policymakers and drug developers can use the indices to help evaluate and prioritise initiatives in the effort against antimicrobial resistance.

Risk factors for carriage of antimicrobial-resistant Salmonella spp and Escherichia coli in pet dogs from volunteer households in Ontario, Canada, in 2005 and 2006.

OBJECTIVE To determine pet-related management factors associated with the carriage of antimicrobial-resistant Salmonella spp and Escherichia coli in a population of pet dogs. SAMPLE 138 dogs from 84 households in Ontario, Canada. PROCEDURES From October 2005 through May 2006, dogs and households in Ontario, Canada, were recruited to participate in a cross-sectional study. Fecal samples were submitted for culture of Salmonella spp and E coli, which provided 515 bacterial isolates for antimicrobial susceptibility testing. Multilevel logistic regression models with random effects for household and dog were created to identify pet-related management factors associated with antimicrobial resistance. RESULTS Bacterial species, feeding a homemade diet or adding homemade food to the diet, feeding a raw diet or adding anything raw to the diet, feeding a homemade raw food diet, and feeding raw chicken in the past week were significant risk factors for antimicrobial resistance in this population of dogs. CONCLUSIONS AND CLINICAL RELEVANCE In this study, several potentially important pet-related risk factors for the carriage of antimicrobial-resistant Salmonella spp and E coli in pet dogs were identified. Further evaluation of risk factors for antimicrobial resistance in dogs may lead to development of evidence-based guidelines for safe and responsible dog ownership and management to protect the public, especially pet owners who are immunocompromised.

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.

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.

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.

Burden of self-reported acute gastrointestinal illness in Cuba.

Acute gastrointestinal illness is an important public-health issue worldwide. Burden-of-illness studies have not previously been conducted in Cuba. The objective of the study was to determine the magnitude, distribution, and burden of self-reported acute gastrointestinal illness in Cuba. A retrospective, cross-sectional survey was conducted in three sentinel sites during June-July 2005 (rainy season) and during November 2005-January 2006 (dry season). Households were randomly selected from a list maintained by the medical offices in each site. One individual per household was selected to complete a questionnaire in a face-to-face interview. The case definition was three or more bouts of loose stools in a 24-hour period within the last 30 days. In total, 97.3% of 6,576 interviews were completed. The overall prevalence of acute gastrointestinal illness was 10.6%. The risk of acute gastrointestinal illness was higher during the rainy season (odds ratio [OR]=3.85, 95% confidence interval [CI] 3.18-4.66) in children (OR=3.12, 95% CI 2.24-4.36) and teens (OR=2.27, 95% CI 1.51-3.41) compared to people aged 25-54 years, in males (OR=1.24, 95% CI 1.04-1.47), and in the municipality of Santiago de Cuba (OR=1.33, 95% CI 1.11-1.61). Of 680 cases, 17.1-38.1% visited a physician, depending on sentinel site. Of the cases who visited a physician, 33.3-53.9% were requested to submit a stool sample, and of those, 72.7-100.0% complied. Of the cases who sought medical care, 16.7-61.5% and 0-31.6% were treated with antidiarrhoeals and antibiotics respectively. Acute gastrointestinal illness represented a substantial burden of health compared to developed countries. Targeting the identified risk factors when allocating resources for education, food safety, and infrastructure might lower the morbidity associated with acute gastrointestinal illness.