Background Assessment of the burden of disease due to antimicrobial-resistant Escherichia coli infections facilitates understanding the scale of the problem and potential impacts, and comparison to other diseases, which allows prioritization of research, surveillance, and funding. Using systematic review and meta-analysis methodology, the objectives were to evaluate whether humans with antimicrobial-resistant E. coli infections experience increases in measures of health or healthcare system burden when compared to susceptible E. coli infections. Methods Comprehensive literature searches were performed in four primary and seven grey literature databases. Analytic observational studies of human E. coli infections that assessed the impact of resistance to third/fourth/fifth-generation cephalosporins, resistance to quinolones, and/or multidrug resistance on mortality, treatment failure, length of hospital stay and/or healthcare costs were included. Two researchers independently performed screening, data extraction, and risk of bias assessment. When possible, random effect meta-analyses followed by assessment of the confidence in the cumulative evidence were performed for mortality and length of hospital stay outcomes, and narrative syntheses were performed for treatment failure and healthcare costs. Results Literature searches identified 14,759 de-duplicated records and 76 articles were included. Based on 30-day and all-cause mortality meta-analyses, regardless of the type of resistance, there was a significant increase in the odds of dying with resistant E. coli infections compared to susceptible infections. A summary mean difference was not presented for total length of hospital stay meta-analyses due to substantial to considerable heterogeneity. Since small numbers of studies contributed to meta-analyses for bacterium-attributable mortality and post-infection length of hospital stay, the summary results should be considered with caution. Studies contributing results for treatment failure and healthcare costs had considerable variability in definitions and reporting. Conclusions Overall, resistant E. coli infections were associated with significant 30-day and all-cause mortality burden. More research and/or improved reporting are necessary to facilitate quantitative syntheses of bacterium-attributable mortality, length of hospital stay, and hospital costs. Protocol Registration PROSPERO CRD42018111197.

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.

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.

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