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.

Patterns of enteric infections in a population-wide cohort study of sequelae, British Columbia, Canada.

We assessed patterns of enteric infections caused by 14 pathogens, in a longitudinal cohort study of sequelae in British Columbia (BC) Canada, 2005-2014. Our population cohort of 5.8 million individuals was followed for an average of 7.5 years/person; during this time, 40 523 individuals experienced 42 308 incident laboratory-confirmed, provincially reported enteric infections (96.4 incident infections per 100 000 person-years). Most individuals (38 882/40 523; 96%) had only one, but 4% had multiple concurrent infections or more than one infection across the study. Among individuals with more than one infection, the pathogens and combinations occurring most frequently per individual matched the pathogens occurring most frequently in the BC population. An additional 298 557 new fee-for-service physician visits and hospitalisations for enteric infections, that did not coincide with a reported enteric infection, also occurred, and some may be potentially unreported enteric infections. Our findings demonstrate that sequelae risk analyses should explore the possible impacts of multiple infections, and that estimating risk for individuals who may have had a potentially unreported enteric infection is warranted.

Serum amyloid A and fibrinogen as markers for early detection of surgical site infection associated with internal fixation in the horse.

The objective of this study was to determine the diagnostic ability of serum amyloid A (SAA) and fibrinogen for early detection of surgical site infection (SSI) after equine internal fixation. Horses undergoing internal fixation for fracture, arthrodesis, or osteotomy with internal fixation for limb deformity were included in the study. SAA and fibrinogen were measured on blood samples preoperatively and on days 1, 3, 5, 7, 10, and 14 postoperatively. Statistical analysis included use of Spearman's rank correlation, logistic regression, and calculating the area under the receiver operating characteristic (ROC) curve. SAA and fibrinogen measurements were both associated with SSI, with SAA being considered an excellent marker (area under the ROC curve 0.8) and fibrinogen being considered acceptable (<0.8). As the amount of time postoperatively increased, SAA elevations indicated a higher likelihood of SSI (area under the ROC curve 0.8 compared with fibrinogen 0.7). SAA and fibrinogen were predictive markers of SSI and SAA is of greater diagnostic utility when compared with fibrinogen. Persistent elevations of SAA postoperatively are associated with the development of SSI. Serial monitoring of SAA can be used to help predict the development of SSI in horses undergoing internal fixation. This may lead to earlier suspicion, and therefore recognition and treatment of SSI.

Increasing incidence and antimicrobial resistance in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. METHODS: We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). RESULTS: We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. CONCLUSIONS: Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.

Escherichia coli bloodstream infections in the western interior of British Columbia, Canada: a population-based cohort study.

Our population-based study objectives were to describe characteristics and outcomes of Escherichia coli bloodstream infections (BSIs), and to evaluate factors associated with outcomes. We included incident E. coli BSIs from western interior residents (British Columbia, Canada; 04/2010-03/2020). We obtained data including patient demographics, location of onset, infection focus, Charlson comorbidity index (CCI), antimicrobial resistance, 30-day all-cause mortality and length of hospital stay (LOS). Using multivariable logistic regression models fitted with generalised estimating equations, we estimated factors associated with 30-day mortality and long post-infection LOS (>75th percentile). We identified 1080 incident E. coli BSIs in 1009 patients. The crude incidence and 30-day mortality rates were 59.1 BSIs and 6.8 deaths/100 000 person-years, respectively. The 30-day case fatality risk was 11.5%. Compared to community-acquired E. coli BSIs, either healthcare-associated or nosocomial cases had higher odds of 30-day mortality. Older cases, non-urogenital BSI foci and CCI ⩾ 3 had higher odds of 30-day mortality compared to younger cases, urogenital foci and CCI < 3. In patients that survived to discharge, those with extended-spectrum ß-lactamase (ESBL)-producing E. coli BSIs, nosocomial BSIs, and CCI ⩾ 3 had higher odds of long post-infection LOS compared to those with non-ESBL-producing, community-acquired and healthcare-associated, and CCI < 3. There is a substantial disease burden from E. coli BSIs.

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.

Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study.

BACKGROUND: Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. METHODS: During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. RESULTS: From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. CONCLUSIONS: In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.

Efficacy of Borrelia burgdorferi vaccine in dogs in North America: A systematic review and meta-analysis.

BACKGROUND: Lyme borreliosis, a tick-borne disease, is endemic to some parts of North America and is an emerging disease in other parts of the world. Vaccination is an increasingly common, although controversial, method used in the prevention of Lyme disease in dogs; the reported efficacies of Borrelia burgdorferi vaccines in dogs are highly variable, ranging from 50% to 100%. OBJECTIVES: To determine the efficacy of vaccines for prevention of Lyme disease in dogs in North America. METHODS: Experimental and observational study designs were eligible for inclusion. The outcome of interest was the reduction of incidence of clinical illness after exposure to B. burgdorferi. Electronic databases searched were MEDLINE, Web of Science, and Centre for Agricultural Biosciences Abstracts. Clinical signs were extracted as dichotomous outcomes: lameness, anorexia, pyrexia, depression, and lymphadenopathy. Study quality was assessed using tools from the Cochrane collaboration. RESULTS: In total, 3 observational studies and 13 challenge trials were included. None of the challenge trials assessed lymphadenopathy, but for each of the remaining 4 clinical signs, a meta-analysis was performed. Compared to unvaccinated dogs, vaccinated dogs had a reduced odds of developing lameness, depression, pyrexia, and anorexia (odds ratio: 0.15-0.23). CONCLUSIONS AND CLINICAL IMPORTANCE: Based on the quantitative synthesis of results from challenge studies, vaccinated dogs are less likely to develop clinical signs after exposure to B. burgdorferi compared to unvaccinated dogs. These results should be interpreted with caution, however, as several shortcomings related to quality and study design were identified. Future studies should focus on larger sample sizes in field conditions.

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 ß-lactams with ß-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 ß-lactams with ß-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.

Colic in equine neonates: 137 cases (2000-2010).

OBJECTIVE: To document causes of colic in equine neonates, evaluate clinical features of neonates managed medically versus surgically, determine short- and long-term survival rates for neonates with specific medical and surgical lesions, and assess ability of patients to achieve intended use. DESIGN: Retrospective case series. ANIMALS: 137 client-owned equine neonates (< 30 days old) with a history of colic or signs of colic within 1 hour after hospital admission examined between 2000 and 2010. PROCEDURES: Signalment, history, results of physical examination, laboratory data, ancillary diagnostic tests, details of treatment, primary diagnosis, concurrent diseases and short-term survival rate were obtained from the medical records. Long-term follow-up information was obtained through phone survey. RESULTS: 137 neonates with colic were included. The majority (122 [89%]) of neonates were managed medically. The 3 most common diagnoses associated with colic were enterocolitis (37 [27%]), meconium-associated colic (27 [20%]), and transient medical colic (26 [19%]). The most common reason for surgery was small intestinal strangulating obstruction, and these neonates were more likely to have severe, continuous pain and were less responsive to analgesics. Concurrent diseases were common (87 [64%]) but did not significantly impact survival rate. Short-term survival rate was not significantly different between medically (75%) and surgically (73%) managed neonates. Long-term survival rate was excellent (66/71 [93%]) for horses that survived to hospital discharge. Most neonates surviving to maturity were used as intended (49/59 [83%]). CONCLUSIONS AND CLINICAL RELEVANCE: Most neonates examined for signs of colic can be managed medically. Short-term survival rate in medically and surgically treated neonates was good. Long-term survival rate of foals discharged from the hospital was excellent, with most achieving intended use.