{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:28:36Z","timestamp":1792466916966,"version":"4.5.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W026643\/1"],"award-info":[{"award-number":["MR\/W026643\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222051\/Z\/20\/Z"],"award-info":[{"award-number":["222051\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018336","name":"National Institute for Health Research Health Protection Research Unit","doi-asserted-by":"publisher","award":["NIHR200915"],"award-info":[{"award-number":["NIHR200915"]}],"id":[{"id":"10.13039\/100018336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000286","name":"British Academy","doi-asserted-by":"publisher","award":["GCPS2\\100009"],"award-info":[{"award-number":["GCPS2\\100009"]}],"id":[{"id":"10.13039\/501100000286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antimicrobial Resistance (AMR) is a global public health crisis. Evaluating intervention impact requires accurate estimates of how the AMR burden will change over time, given likely demographic shifts. This study aimed to provide an estimate of future AMR burden in Europe, investigating resistance variation by age and sex and the impact of interventions to achieve the proposed United Nations (UN) political declaration targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>Using data from 12,807,473 bloodstream infection (BSI) susceptibility tests from routine surveillance in Europe, we estimate age- and sex-specific rates of change in BSI incidence for the 8 bacteria included in European Antimicrobial Resistance Surveillance Network (EARS-Net) surveillance over 2015\u20132019. This was used to project incidence rates by age and sex for 2022\u20132050 and, with demographic projections, to generate estimates of BSI burden (2022\u20132050). Two Bayesian hierarchical models were fitted across 38 bacteria-antibiotic combinations to the 2015\u20132019 resistance proportion of BSI by year and at the country-level with and without age and sex disaggregation. Inputting the incidence estimates into the \u201cagesex\u201d and \u201cbase\u201d model, respectively, we sampled 1,000 model estimates of resistant BSI burden by age, sex, and country to determine the importance of age and sex disaggregation. We explored Intervention scenarios consisting of a 1, 5, or 20 per 100,000 per year reduction in infection incidence rate of change or 5 per 100,000 per year reduction in those older than 64 years.<\/jats:p>\n                    <jats:p>\n                      Overall, in Europe, BSI incidence rates are predicted to increase more in men than women across 6 of the 8 bacteria (\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      and\n                      <jats:italic>Enterococcus faecium<\/jats:italic>\n                      were the exception) and are projected to increase more dramatically in older age groups (74+ years) but stabilise or decline in younger age groups. We project huge country-level variation in resistance burden to 2050, with opposing trends in different countries for the same bacteria-antibiotic combinations (e.g., aminoglycoside-resistant\n                      <jats:italic>Acinetobacter spp.<\/jats:italic>\n                      ranged from a relative difference of 0.34 to 15.38 by 2030).\n                    <\/jats:p>\n                    <jats:p>Not accounting for age and sex results in differing resistance burden projections, with 47% of bacteria-antibiotic combinations estimated to have fewer resistant BSIs by 2030 compared to a model with age and sex. Not including age or sex resistance patterns results in fewer male cases for 76% (29\/38) of the combinations compared to 11% (4\/38) for women. We also saw age-based associations in projections with bigger differences at older ages.<\/jats:p>\n                    <jats:p>Achieving a 10% reduction in resistant BSI incidence by 2030 (equivalent to the UN 10% mortality target) was possible only for 68.4% (26\/38) of bacteria-antibiotic combinations even with large reductions in BSI incidence rate of change of \u221220 per 100,000 per year. In some cases, a 10% reduction was followed by a rebound, with the resistant BSI burden exceeding previous levels by 2050. Limitations include reliance on European data and current trends, and the exclusion of factors such as comorbidities or ethnicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Including country-specific, age- and sex-specific resistance levels alongside projected demographic shifts has a large impact on resistant BSI burden projections in Europe to 2030. Reducing this AMR infection burden by 10% will require substantial reductions in infection incidence rates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004579","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:26:12Z","timestamp":1762280772000},"page":"e1004579","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Combining demographic shifts with age-based resistance prevalence to estimate future antimicrobial resistance burden in Europe and implications for targets: A modelling study"],"prefix":"10.1371","volume":"22","author":[{"given":"Naomi R.","family":"Waterlow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6499-7522","authenticated-orcid":true,"given":"Clare I. R.","family":"Chandler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben S.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8639-9846","authenticated-orcid":true,"given":"Catrin E.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie V.","family":"Robotham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6761-2325","authenticated-orcid":true,"given":"Benn","family":"Sartorius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sharland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-9896","authenticated-orcid":true,"given":"Gwenan M.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"issue":"3","key":"pmed.1004579.ref001","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1004301","article-title":"Antimicrobial resistance prevalence in bloodstream infection in 29 European countries by age and sex: an observational study","volume":"21","author":"NR Waterlow","year":"2024","journal-title":"PLoS Med"},{"issue":"1821","key":"pmed.1004579.ref002","first-page":"20143085","article-title":"Evolution of the immune system in humans from infancy to old age","volume":"282","author":"AK Simon","year":"2015","journal-title":"Proc Biol Sci"},{"key":"pmed.1004579.ref003","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fmed.2019.00118","article-title":"Infections in the elderly critically-Ill patients","volume":"6","author":"M Esme","year":"2019","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"pmed.1004579.ref004","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","article-title":"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","volume":"19","author":"A Cassini","year":"2019","journal-title":"Lancet Infect Dis"},{"issue":"1","key":"pmed.1004579.ref005","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12961-020-00549-1","article-title":"Strengthening the science of addressing antimicrobial resistance: a framework for planning, conducting and disseminating antimicrobial resistance intervention research","volume":"18","author":"S Rogers Van Katwyk","year":"2020","journal-title":"Health Res Policy Syst"},{"issue":"10459","key":"pmed.1004579.ref006","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990\u20132021: a systematic analysis with forecasts to 2050","volume":"404","author":"M Naghavi","year":"2024","journal-title":"Lancet"},{"key":"pmed.1004579.ref007","article-title":"Population-based study of bloodstream infection incidence and mortality rates, Finland, 2004\u20132018","volume":"27","author":"KSK Kontula","year":"2021","journal-title":"Emerg Infect Dis"},{"issue":"10","key":"pmed.1004579.ref008","doi-asserted-by":"crossref","first-page":"2200519","DOI":"10.2807\/1560-7917.ES.2023.28.10.2200519","article-title":"Incidence, aetiology and temporal trend of bloodstream infections in southern Sweden from 2006 to 2019: a population-based study","volume":"28","author":"O Ljungquist","year":"2023","journal-title":"Euro Surveill"},{"key":"pmed.1004579.ref009","doi-asserted-by":"crossref","first-page":"875","DOI":"10.3201\/eid2505.181773","article-title":"Age-dependent increase in incidence of Staphylococcus aureus Bacteremia, Denmark, 2008\u20132015","volume":"25","author":"L Thorlacius-Ussing","year":"2019","journal-title":"Emerg Infect Dis"},{"issue":"5","key":"pmed.1004579.ref010","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jinf.2011.03.003","article-title":"Staphylococcus aureus bacteraemia\u2014nationwide assessment of treatment adequacy and outcome","volume":"62","author":"H Asgeirsson","year":"2011","journal-title":"J Infect"},{"key":"pmed.1004579.ref011","unstructured":"UK Health Security Agency. Annual epidemiological commentary: gram-negative, MRSA, MSSA bacteraemia and C. difficile infections, up to and including financial year 2021 to 2022. 2022 [cited 2023 Jun 7]. GOV.UK [Internet]. Available from: https:\/\/www.gov.uk\/government\/statistics\/mrsa-mssa-and-e-coli-bacteraemia-and-c-difficile-infection-annual-epidemiological-commentary\/annual-epidemiological-commentary-gram-negative-mrsa-mssa-bacteraemia-and-c-difficile-infections-up-to-and-including-financial-year-2021-to-2022"},{"issue":"46","key":"pmed.1004579.ref012","doi-asserted-by":"crossref","first-page":"2002094","DOI":"10.2807\/1560-7917.ES.2021.26.46.2002094","article-title":"Staphylococcus aureus bloodstream infections: diverging trends of meticillin-resistant and meticillin-susceptible isolates, EU\/EEA, 2005 to 2018","volume":"26","author":"C Gagliotti","year":"2021","journal-title":"Euro Surveill"},{"issue":"10","key":"pmed.1004579.ref013","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/S1473-3099(18)30353-0","article-title":"Trends over time in Escherichia coli bloodstream infections, urinary tract infections, and antibiotic susceptibilities in Oxfordshire, UK, 1998\u20132016: a study of electronic health records","volume":"18","author":"K-D Vihta","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"pmed.1004579.ref014","unstructured":"O\u2019Neill J. Tackling drug-resistant infections globally: final report and recommendations the review on antimicrobial resistance chaired by Jim O\u2019Neill; 2016. Available from: https:\/\/amr-review.org\/sites\/default\/files\/160525_Final%20paper_with%20cover.pdf"},{"key":"pmed.1004579.ref015","unstructured":"UN. Political declaration of the high-level meeting on antimicrobial resistance. Available from: https:\/\/www.un.org\/pga\/wp-content\/uploads\/sites\/108\/2024\/09\/FINAL-Text-AMR-to-PGA.pdf"},{"issue":"9","key":"pmed.1004579.ref016","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/S1473-3099(17)30325-0","article-title":"Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis","volume":"17","author":"D Baur","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"pmed.1004579.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jhin.2021.04.030","article-title":"Linking infection control to clinical management of infections to overcome antimicrobial resistance","volume":"114","author":"E Tacconelli","year":"2021","journal-title":"J Hosp Infect"},{"key":"pmed.1004579.ref018","unstructured":"Improving infection prevention and control to prevent the spread of antimicrobial resistance [cited 2025 Jan 31]. Available from: https:\/\/www.who.int\/europe\/activities\/improving-infection-prevention-and-control-to-prevent-the-spread-of-antimicrobial-resistance"},{"issue":"7","key":"pmed.1004579.ref019","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00355-19","article-title":"The microbiology of bloodstream infection: 20-year trends from the SENTRY antimicrobial surveillance program","volume":"63","author":"DJ Diekema","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"pmed.1004579.ref020","author":"R Core Team","year":"2021"},{"key":"pmed.1004579.ref021","unstructured":"European Centre for Disease Prevention and Control. The European surveillance system (TESSy) [cited 2022 Jan 13]. Available from: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/european-surveillance-system-tessy"},{"key":"pmed.1004579.ref022","unstructured":"External quality assessment of laboratory performance\u2014European antimicrobial resistance surveillance network (EARS-Net), 2018. In: European Centre for Disease Prevention and Control [Internet]; 2019 [cited 2022 Nov 7]. Available from: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/external-quality-assessment-laboratory-performance-european-antimicrobial-0"},{"key":"pmed.1004579.ref023","author":"European Committee on Antimicrobial Susceptibility Testing (EUCAST)","year":"2017"},{"key":"pmed.1004579.ref024","unstructured":"EARS-Net reporting protocol 2022. In: European Centre for Disease Prevention and Control [Internet]; 2022 [cited 2022 Oct 5]. Available from: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/ears-net-reporting-protocol-2022"},{"key":"pmed.1004579.ref025","unstructured":"Central Asian and European surveillance of Antimicrobial Resistance (CAESAR), European Antimicrobial Resistance Surveillance Network (EARS-Net). Antimicrobial resistance surveillance in Europe\u20142023; 2023. Available from: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/antimicrobial-resistance-surveillance-europe-2023"},{"key":"pmed.1004579.ref026","unstructured":"Eurostat. Population projections in the EU; 2020 [cited 2022 Sep 5]. Available from: https:\/\/ec.europa.eu\/eurostat\/statistics-explained\/index.php?title=Population_projections_in_the_EU"},{"key":"pmed.1004579.ref027","unstructured":"Office for National Statistics. Principal projection\u2014UK population in age groups; 2022 [cited 2023 Feb 9]. Available from: https:\/\/www.ons.gov.uk\/peoplepopulationandcommunity\/populationandmigration\/populationprojections\/datasets\/tablea21principalprojectionukpopulationinagegroups"},{"issue":"1","key":"pmed.1004579.ref028","doi-asserted-by":"crossref","DOI":"10.1093\/jacamr\/dlae210","article-title":"Observational study of antibiotic prescribing patterns by age and sex in primary care in England: why we need to take this variation into account to evaluate antibiotic stewardship and predict AMR variation","volume":"7","author":"NR Waterlow","year":"2025","journal-title":"JAC Antimicrob Resist"},{"key":"pmed.1004579.ref029","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.64139","article-title":"Antimicrobial resistance and COVID-19: intersections and implications","volume":"10","author":"GM Knight","year":"2021","journal-title":"Elife"},{"issue":"1","key":"pmed.1004579.ref030","article-title":"brms: an R package for bayesian multilevel models using Stan","volume":"80","author":"P-C B\u00fcrkner","year":"2017","journal-title":"J Stat Soft"},{"key":"pmed.1004579.ref031","unstructured":"ECDC. Surveillance atlas of infectious diseases; 2023 [cited 2023 Feb 23]. Available from: https:\/\/atlas.ecdc.europa.eu\/public\/index.aspx?Dataset=27&HealthTopic=4"},{"issue":"23","key":"pmed.1004579.ref032","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1016\/j.vaccine.2012.03.019","article-title":"Health and economic impact of the seasonal influenza vaccination programme in England","volume":"30","author":"M Baguelin","year":"2012","journal-title":"Vaccine"},{"key":"pmed.1004579.ref033","unstructured":"ECDC. Estimated incidence of bloodstream infections with three key pathogens in the EU\/EEA in 2019; 2023 [cited 2025 Jan 31]. Available from: https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/bloodstream-infections-estimated-incidence-2019.pdf"},{"key":"pmed.1004579.ref034","author":"UK Health Security Agency","year":"2022"},{"issue":"6","key":"pmed.1004579.ref035","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.ajic.2014.02.014","article-title":"A multitiered strategy of simulation training, kit consolidation, and electronic documentation is associated with a reduction in central line-associated bloodstream infections","volume":"42","author":"GB Allen","year":"2014","journal-title":"Am J Infect Control"},{"issue":"11","key":"pmed.1004579.ref036","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.ajic.2014.07.003","article-title":"A multifactorial action plan improves hand hygiene adherence and significantly reduces central line-associated bloodstream infections","volume":"42","author":"L Johnson","year":"2014","journal-title":"Am J Infect Control"},{"issue":"7","key":"pmed.1004579.ref037","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1097\/CCM.0b013e3181a02d8f","article-title":"Impact of a prevention strategy targeting hand hygiene and catheter care on the incidence of catheter-related bloodstream infections","volume":"37","author":"W Zingg","year":"2009","journal-title":"Crit Care Med"},{"issue":"4","key":"pmed.1004579.ref038","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s40258-022-00728-x","article-title":"Modelling the future clinical and economic burden of antimicrobial resistance: the feasibility and value of models to inform policy","volume":"20","author":"NT Hillock","year":"2022","journal-title":"Appl Health Econ Health Policy"},{"key":"pmed.1004579.ref039","author":"WHO","year":"2020"},{"issue":"8","key":"pmed.1004579.ref040","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1080\/03007995.2022.2081454","article-title":"Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review","volume":"38","author":"SV Sylvester","year":"2022","journal-title":"Curr Med Res Opin"},{"issue":"9","key":"pmed.1004579.ref041","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.cmi.2023.05.015","article-title":"Markers of epidemiological success of methicillin-resistant Staphylococcus aureus isolates in European populations","volume":"29","author":"VO Baede","year":"2023","journal-title":"Clin Microbiol Infect"},{"issue":"6","key":"pmed.1004579.ref042","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s41579-019-0315-1","article-title":"Population genomics of Klebsiella pneumoniae","volume":"18","author":"KL Wyres","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"15","key":"pmed.1004579.ref043","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1717295115","article-title":"Global increase and geographic convergence in antibiotic consumption between 2000 and 2015","volume":"115","author":"EY Klein","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pmed.1004579.ref044","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1093\/jac\/dkab050","article-title":"Hospital antibiotic prescribing patterns in adult patients according to the WHO Access, Watch and Reserve classification (AWaRe): results from a worldwide point prevalence survey in 69 countries","volume":"76","author":"Global-PPS network","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"pmed.1004579.ref045","unstructured":"European Medicines Agency, European Surveillance of Veterinary Antimicrobial Consumption. Sales of veterinary antimicrobial agents in 31 European countries in 2019 and 2020. 2021. Report No.: EMA\/58183\/2021."},{"key":"pmed.1004579.ref046","unstructured":"UK Health Security Agency (UKHSA). English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) report 2022 to 2023. 2023. Available from: https:\/\/assets.publishing.service.gov.uk\/media\/6734e208b613efc3f1823095\/ESPAUR-report-2023-2024.pdf"},{"key":"pmed.1004579.ref047","unstructured":"Global research on antimicrobial resistance (GRAM). 2025. Available from: https:\/\/www.tropicalmedicine.ox.ac.uk\/gram"},{"issue":"3","key":"pmed.1004579.ref048","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jinf.2020.10.040","article-title":"Impact of low blood culture usage on rates of antimicrobial resistance","volume":"82","author":"C Lim","year":"2021","journal-title":"J Infect"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:26:24Z","timestamp":1762280784000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004579"}},"subtitle":[],"editor":[{"given":"Rebecca F.","family":"Grais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004579","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]}}}