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

Alessandro Cassini, Liselotte Diaz Högberg, Diamantis Plachouras, Annalisa Quattrocchi, Ana Hoxha, Gunnar Skov Simonsen, Mélanie Colomb-Cotinat, Mirjam E Kretzschmar, Brecht Devleesschauwer, Michele Cecchini, Driss Ait Ouakrim, Tiago Cravo Oliveira, Marc J Struelens, Carl Suetens, Dominique L Monnet, Burden of AMR Collaborative Group, Reinhild Strauss, Karl Mertens, Thomas Struyf, Boudewijn Catry, Katrien Latour, Ivan N Ivanov, Elina G Dobreva, Arjana Tambic Andraševic, Silvija Soprek, Ana Budimir, Niki Paphitou, Helena Žemlicková, Stefan Schytte Olsen, Ute Wolff Sönksen, Pille Märtin, Marina Ivanova, Outi Lyytikäinen, Jari Jalava, Bruno Coignard, Tim Eckmanns, Muna Abu Sin, Sebastian Haller, George L Daikos, Achilleas Gikas, Sotirios Tsiodras, Flora Kontopidou, Ákos Tóth, Ágnes Hajdu, Ólafur Guólaugsson, Karl G Kristinsson, Stephen Murchan, Karen Burns, Patrizio Pezzotti, Carlo Gagliotti, Uga Dumpis, Agne Liuimiene, Monique Perrin, Michael A Borg, Sabine C de Greeff, Jos Cm Monen, Mayke Bg Koek, Petter Elstrøm, Dorota Zabicka, Aleksander Deptula, Waleria Hryniewicz, Manuela Caniça, Paulo Jorge Nogueira, Paulo André Fernandes, Vera Manageiro, Gabriel A Popescu, Roxana I Serban, Eva Schréterová, Slavka Litvová, Mária Štefkovicová, Jana Kolman, Irena Klavs, Aleš Korošec, Belén Aracil, Angel Asensio, María Pérez-Vázquez, Hanna Billström, Sofie Larsson, Jacqui S Reilly, Alan Johnson, Susan Hopkins, Alessandro Cassini, Liselotte Diaz Högberg, Diamantis Plachouras, Annalisa Quattrocchi, Ana Hoxha, Gunnar Skov Simonsen, Mélanie Colomb-Cotinat, Mirjam E Kretzschmar, Brecht Devleesschauwer, Michele Cecchini, Driss Ait Ouakrim, Tiago Cravo Oliveira, Marc J Struelens, Carl Suetens, Dominique L Monnet, Burden of AMR Collaborative Group, Reinhild Strauss, Karl Mertens, Thomas Struyf, Boudewijn Catry, Katrien Latour, Ivan N Ivanov, Elina G Dobreva, Arjana Tambic Andraševic, Silvija Soprek, Ana Budimir, Niki Paphitou, Helena Žemlicková, Stefan Schytte Olsen, Ute Wolff Sönksen, Pille Märtin, Marina Ivanova, Outi Lyytikäinen, Jari Jalava, Bruno Coignard, Tim Eckmanns, Muna Abu Sin, Sebastian Haller, George L Daikos, Achilleas Gikas, Sotirios Tsiodras, Flora Kontopidou, Ákos Tóth, Ágnes Hajdu, Ólafur Guólaugsson, Karl G Kristinsson, Stephen Murchan, Karen Burns, Patrizio Pezzotti, Carlo Gagliotti, Uga Dumpis, Agne Liuimiene, Monique Perrin, Michael A Borg, Sabine C de Greeff, Jos Cm Monen, Mayke Bg Koek, Petter Elstrøm, Dorota Zabicka, Aleksander Deptula, Waleria Hryniewicz, Manuela Caniça, Paulo Jorge Nogueira, Paulo André Fernandes, Vera Manageiro, Gabriel A Popescu, Roxana I Serban, Eva Schréterová, Slavka Litvová, Mária Štefkovicová, Jana Kolman, Irena Klavs, Aleš Korošec, Belén Aracil, Angel Asensio, María Pérez-Vázquez, Hanna Billström, Sofie Larsson, Jacqui S Reilly, Alan Johnson, Susan Hopkins

Abstract

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.

Funding: European Centre for Disease Prevention and Control.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Infections with antibiotic-resistant bacteria, EU and European Economic Area, 2015 Diameter of bubbles represents the number of disability-adjusted life-years. ColRACI=colistin-resistant Acinetobacter spp. CRACI=carbapenem-resistant Acinetobacter spp. MDRACI=multidrug-resistant Acinetobacter spp. VRE=vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. ColREC=colistin-resistant Escherichia coli. CREC=carbapenem-resistant E coli. 3GCREC=third-generation cephalosporin-resistant E coli. ColRKP=colistin-resistant Klebsiella pneumoniae. CRKP=carbapenem-resistant K pneumoniae. 3GCRKP=third-generation cephalosporin-resistant K pneumoniae. ColRPA=colistin-resistant Pseudomonas aeruginosa. CRPA=carbapenem-resistant P aeruginosa. MDRPA=multidrug-resistant P aeruginosa. MRSA=meticillin-resistant Staphylococcus aureus. PRSP=penicillin-resistant Streptococcus pneumoniae. PMRSP=penicillin-resistant and macrolide-resistant S pneumoniae.
Figure 2
Figure 2
Model estimates of the burden of infections with antibiotic-resistant bacteria of public health importance in DALYs, by age group, EU and European Economic Area, 2015 Error bars are 95% uncertainty intervals. DALYs=disability-adjusted life-years. *Excludes those resistant to carbapenem or colistin. †In 2015, most of the third-generation cephalosporin-resistant E coli (88·6%) and K pneumoniae (85·3%) isolates reported to the European Antimicrobial Resistance Surveillance Network produced an extended-spectrum β-lactamase.
Figure 3
Figure 3
Burden of infections with antibiotic-resistant bacteria in DALYs, EU and European Economic Area, 2015 Error bars are 95% uncertainty intervals. Greece did not report data on S pneumoniae isolates to the European Antimicrobial Resistance Surveillance Network in 2015. DALY rates are age-standardised to limit the effect of demographic differences across countries; numbers of cases and deaths are not age-standardised. DALYs=disability-adjusted life-years. *Excludes those resistant to carbapenem or colistin. †In 2015, most of the third-generation cephalosporin-resistant E coli (88·6%) and K pneumoniae (85·3%) isolates reported to the European Antimicrobial Resistance Surveillance Network produced an extended-spectrum β-lactamase.
Figure 4
Figure 4
Model estimates of the burden of infections with selected antibiotic-resistant bacteria of public health importance in DALYs per 100 000 population, EU and European Economic Area, 2015 Greece did not report data on S pneumoniae isolates to the European Antimicrobial Resistance Surveillance Network in 2015. DALYs=disability-adjusted life-years.

References

    1. European Commission A European one health action plan against antimicrobial resistance (AMR) 2017.
    1. WHO . WHO; Geneva: 2015. Global Action Plan on Antimicrobial Resistance.
    1. Wernli D, Jorgensen PS, Harbarth S. Antimicrobial resistance: the complex challenge of measurement to inform policy and the public. PLoS Med. 2017;14:e1002378.
    1. de Kraker ME, Stewardson AJ, Harbarth S. Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Med. 2016;13:e1002184.
    1. Stewardson AJ, Allignol A, Beyersmann J. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study. Euro Surveill. 2016;21:30319.
    1. ECDC. CVMP ECDC, EFSA and EMA Joint Scientific Opinion on a list of outcome indicators as regards surveillance of antimicrobial resistance and antimicrobial consumption in humans and food-producing animals. EFSA J. 2017;15:e05017.
    1. Kretzschmar M, Mangen MJ, Pinheiro P. New methodology for estimating the burden of infectious diseases in Europe. PLoS Med. 2012;9:e1001205.
    1. Murray CJ, Ezzati M, Flaxman AD. GBD 2010: design, definitions, and metrics. Lancet. 2012;380:2063–2066.
    1. Haagsma JA, Maertens de Noordhout C, Polinder S. Assessing disability weights based on the responses of 30 660 people from four European countries. Popul Health Metr. 2015;13:10.
    1. Cassini A, Plachouras D, Eckmanns T. Burden of six healthcare-associated infections on European population health: estimating incidence-based disability-adjusted life years through a population prevalence-based modelling study. PLoS Med. 2016;13:e1002150.
    1. ECDC Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals. 2013.
    1. ECDC and EMEA Joint Working Group ECDC/EMEA Joint Technical Report. The bacterial challenge: time to react. 2009.
    1. Eurostat Revision of the European standard p opulation. Report of Eurostat's task force. 2013.
    1. ECDC BCoDE toolkit. European Centre for Disease Prevention and Control 2015. 14.
    1. Colzani E, Cassini A, Lewandowski D. A software tool for estimation of burden of infectious diseases in Europe using incidence-based disability adjusted life years. PLoS One. 2017;12:e0170662.
    1. Mangen MJ, Plass D, Havelaar AH. The pathogen- and incidence-based DALY approach: an appropriate [corrected] methodology for estimating the burden of infectious diseases. PLoS One. 2013;8:e79740.
    1. Cassini A, Colzani E, Pini A. Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013. Euro Surveill. 2018;23:17–00454.
    1. CDC . US Department of Health and Human Services, Center of Disease and Infection Control; Atlanta, GA: 2013. Antibiotic resistance threats in the United States.
    1. Colomb-Cotinat M, Lacoste J, Brun-Buisson C, Jarlier V, Coignard B, Vaux S. Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012. Antimicrob Resist Infect Control. 2016;5:56.
    1. Crnich CJ. Impact and management of MRSA in the long-term care setting. Curr Transl Geriatr Exp Gerontol Rep. 2013;2:125–135.
    1. Public Health Agency of Sweden and National Veterinary Institute Swedres-Svarm 2016. Consumption of antibiotics and occurrence of resistance in Sweden.
    1. Sarvikivi E, Ollgren J, Lyytikäinen O. Trends and outcome of healthcare-associated and community-onset bloodstream infections due to Staphylococcus aureus in Finland 2004–2015. European Scientific Conference on Applied Infectious Disease Epidemiology; Stockholm; Nov 6–8, 2017.
    1. Di Ruscio F, Bjornholt JV, Leegaard TM, Moen AEF, de Blasio BF. MRSA infections in Norway: a study of the temporal evolution, 2006–2015. PLoS One. 2017;12:e0179771.
    1. Ministero della Salute Piano Nazionale di Contrasto dell'Antimicrobico-Resistenza (PNCAR) 2017–2020. 2017.
    1. Hellenic Center for Disease Control & Prevention Action Plan “Procrustes”. 2010.
    1. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL, European Survey of Carbapenemase-Producing Enterobacteriaceae working group Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill. 2015;20:30062.
    1. Grundmann H, Glasner C, Albiger B. Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis. 2017;17:153–163.
    1. Umscheid CA, Mitchell MD, Doshi JA, Agarwal R, Williams K, Brennan PJ. Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs. Infect Control Hosp Epidemiol. 2011;32:101–114.
    1. Magiorakos AP, Burns K, Rodriguez Bano J. Infection prevention and control measures and tools for the prevention of entry of carbapenem-resistant Enterobacteriaceae into healthcare settings: guidance from the European Centre for Disease Prevention and Control. Antimicrob Resist Infect Control. 2017;6:113.
    1. Davey P, Marwick CA, Scott CL. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017;2 CD003543.

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