Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012

Abstract Background A study based on 2007 data estimated that 386,000 infections due to multidrug-resistant bacteria (MDRB) occurred in Europe that year and 25,000 patients died from these infections. Our objective was to estimate the morbidity and mortality associated with these infections in France. Methods The MDRB considered were methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci, third-generation cephalosporin-resistant (3GC-R) Escherichia coli and Klebsiella pneumoniae, carbapenem-resistant Klebsiella pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa (CR P. aeruginosa). The number of invasive infections (infections with bacteria isolated from blood or cerebrospinal fluid) due to MDRB, as reported by France to EARS-Net in 2012, was corrected for the coverage of our surveillance network and extrapolated to other body sites using ratios from the French healthcare-associated infections point prevalence survey and the literature. Mortality associated with MDRB infection was estimated using proportions from the literature. Methods and parameters were reviewed by a panel of experts. Results We estimate that 158,000 (127,000 to 245,000) infections due to MDRB occurred in 2012 in France (incidence: 1.48 to 2.85 per 1000 hospital days), including 16,000 invasive infections. MRSA, 3GC-R E. coli and K. pneumoniae were responsible for 120,000 (90,000 to 172,000) infections, i.e., 75% of the total. An estimated 12,500 (11,500 to 17,500) deaths were associated with these infections, including 2,700 associated with invasive infections. MRSA, 3GC-R E. coli and CR P. aeruginosa accounted for 88% of these deaths. Conclusion These first estimates confirm that MRSA, 3GC-R Escherichia coli and Klebsiella pneumoniae account for the largest portion of the morbidity and mortality of infections due to MDRB in France. These results are not directly comparable with the European study because the methodology used differs in many respects. The differences identified between our study and previous studies underline the need to define a standardised protocol for international assessments of the morbidity and mortality of antibiotic resistance. Estimating morbidity and mortality will facilitate communication and awareness in order to reinforce adherence and support of healthcare professionals and policy-makers to MDRB prevention programs

Additional file 1: Tables of Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012

a, b, c. Table a, table b, table c have been added as supplementary material. Table a presents the methodology, parameters and main results of 3 studies estimating the morbidity and mortality of multidrug-resistant bacteria infections : the European study, the US study and our French study. Table b compares the ratios used for estimating the incidence of non-invasive infections in the European study and Santé publique France study. Table c compares the ratios used for estimating mortality associated with infections due to MDRB in the European study and Santé publique France study [31–34]. (PDF 285 kb

Inventory of extended-spectrum-β-lactamase-producing Enterobacteriaceae in France as assessed by a multicenter study

The objective of this study was to perform an inventory of the ESBL-producing Enterobacteriaceae isolates responsible for infections in French hospitals, and to assess the mechanisms associated with ESBL diffusion.200 non-redundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multi-centric study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the Diversilab system. ESBL-encoding plasmids were compared by PCR-based-replicon-typing and plasmid-multi-locus-sequence-typing.CTX-M-15, CTX-M-1, CTX-M-14 and SHV-12 were the most prevalent ESBLs (8 to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2% and 21.8% respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr and aac (3)-II genes were the main plasmid-mediated resistance genes, with prevalence varying between 19.5 and 45% according to the ESBLs. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of few numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species.The prevalence of ESBL subtypes is different according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology and the link observed between the ESBL-encoding plasmids and the bacterial host explain the differences observed in the Enterobacteriaceae species

Defining the scope of the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet): A bottom-up and One Health approach

Background: Building the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) was proposed to strengthen the European One Health antimicrobial resistance (AMR) surveillance approach. Objectives: To define the combinations of animal species/production types/age categories/bacterial species/specimens/antimicrobials to be monitored in EARS-Vet. Methods: The EARS-Vet scope was defined by consensus between 26 European experts. Decisions were guided by a survey of the combinations that are relevant and feasible to monitor in diseased animals in 13 European countries (bottom-up approach). Experts also considered the One Health approach and the need for EARS-Vet to complement existing European AMR monitoring systems coordinated by the ECDC and the European Food Safety Authority (EFSA). Results: EARS-Vet plans to monitor AMR in six animal species [cattle, swine, chickens (broilers and laying hens), turkeys, cats and dogs], for 11 bacterial species (Escherichia coli, Klebsiella pneumoniae, Mannheimia haemolytica, Pasteurella multocida, Actinobacillus pleuropneumoniae, Staphylococcus aureus, Staphylococcus pseudintermedius, Staphylococcus hyicus, Streptococcus uberis, Streptococcus dysgalactiae and Streptococcus suis). Relevant antimicrobials for their treatment were selected (e.g. tetracyclines) and complemented with antimicrobials of more specific public health interest (e.g. carbapenems). Molecular data detecting the presence of ESBLs, AmpC cephalosporinases and methicillin resistance shall be collected too. Conclusions: A preliminary EARS-Vet scope was defined, with the potential to fill important AMR monitoring gaps in the animal sector in Europe. It should be reviewed and expanded as the epidemiology of AMR changes, more countries participate and national monitoring capacities improve

Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods We estimated the incidence of infections with 16 antibiotic resistance-bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011-12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148-763 966) infections with antibiotic-resistant bacteria, of which 63.5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480-38 430) attributable deaths and 874 541 (768 837-989 068) DALYs. The burden for the EU and EEA was highest in infants (aged &lt;1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license