Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Issued Date

2024-09-28

Resource Type

Article

ISSN

01406736

eISSN

1474547X

DOI

10.1016/S0140-6736(24)01867-1

Scopus ID

2-s2.0-85204727310

Pubmed ID

39299261

Journal Title

The Lancet

Volume

404

Issue

10459

Start Page

1199

End Page

1226

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet Vol.404 No.10459 (2024) , 1199-1226

Suggested Citation

Naghavi M., Vollset S.E., Ikuta K.S., Swetschinski L.R., Gray A.P., Wool E.E., Mestrovic T., Smith G., Han C., Hsu R.L., Chalek J., Araki D.T., Chung E., Raggi C., Hayoon A.G., Weaver N.D., Lindstedt P.A., Smith A.E., Bhattacharjee N.V., Runghien T., Ahlstrom A.J., Aravkin A.Y., Dai X., Fuller J.E., He J., Kyu H.H., Lim S.S., Maass K.L., McHugh T.A., Mokdad A.H., Mougin V., Nguyen Q.A.P., Sahu M., Schumacher A.E., Shalev N., Vos T., Wolde A.A., Yuan C.W., Hay S.I., Murray C., Stergachis A., Sartorius B., Iwu C.D., Olivas-Martinez A., Walson J.L., Giannakis K., Altay U., Aguilar G.R., McManigal B., Ekapirat N., Mendes J.A., Srimokla O., Kumaran E.A.P., Lim C., Stoesser N., Walker A.S., Wangrangsimakul T., Cooper B.S., Dolecek C., Fell F., Browne A.J., Allel K., Eyre D.W., Berkley J.A., Dunachie S.J., Roberts T., Turner P., Garcia-Gallo E.E., Perrone C., Pollard A.J., Abdelkader A., Alalalmeh S.O., Hegazi O.E., Shahwan M.J., Shamsi A., Zyoud S.H., Abd-Elsalam S., Aboagye R.G., Adzigbli L.A., Dowou R.K., Abolhassani H., Saghazadeh A., Azadnajafabad S., Rashidi M.M., Moghaddam S.S., Babaei M., Dadras O., Tabatabaei M.S.H.Z., Rahimi-Movaghar V., Shafie M., Sharifan A., Abualruz H., Abubakar U., Abukhadijah H.J., Aburuz S., Nauman J., Abu-Zaid A., Achalapong S., Khusuwan S., Ounchanum P. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. The Lancet Vol.404 No.10459 (2024) , 1199-1226. 1226. doi:10.1016/S0140-6736(24)01867-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/102371

Title

Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Author(s)

Naghavi M.
 Vollset S.E.
 Ikuta K.S.
 Swetschinski L.R.
 Gray A.P.
 Wool E.E.
 Mestrovic T.
 Smith G.
 Han C.
 Hsu R.L.
 Chalek J.
 Araki D.T.
 Chung E.
 Raggi C.
 Hayoon A.G.
 Weaver N.D.
 Lindstedt P.A.
 Smith A.E.
 Bhattacharjee N.V.
 Runghien T.
 Ahlstrom A.J.
 Aravkin A.Y.
 Dai X.
 Fuller J.E.
 He J.
 Kyu H.H.
 Lim S.S.
 Maass K.L.
 McHugh T.A.
 Mokdad A.H.
 Mougin V.
 Nguyen Q.A.P.
 Sahu M.
 Schumacher A.E.
 Shalev N.
 Vos T.
 Wolde A.A.
 Yuan C.W.
 Hay S.I.
 Murray C.
 Stergachis A.
 Sartorius B.
 Iwu C.D.
 Olivas-Martinez A.
 Walson J.L.
 Giannakis K.
 Altay U.
 Aguilar G.R.
 McManigal B.
 Ekapirat N.
 Mendes J.A.
 Srimokla O.
 Kumaran E.A.P.
 Lim C.
 Stoesser N.
 Walker A.S.
 Wangrangsimakul T.
 Cooper B.S.
 Dolecek C.
 Fell F.
 Browne A.J.
 Allel K.
 Eyre D.W.
 Berkley J.A.
 Dunachie S.J.
 Roberts T.
 Turner P.
 Garcia-Gallo E.E.
 Perrone C.
 Pollard A.J.
 Abdelkader A.
 Alalalmeh S.O.
 Hegazi O.E.
 Shahwan M.J.
 Shamsi A.
 Zyoud S.H.
 Abd-Elsalam S.
 Aboagye R.G.
 Adzigbli L.A.
 Dowou R.K.
 Abolhassani H.
 Saghazadeh A.
 Azadnajafabad S.
 Rashidi M.M.
 Moghaddam S.S.
 Babaei M.
 Dadras O.
 Tabatabaei M.S.H.Z.
 Rahimi-Movaghar V.
 Shafie M.
 Sharifan A.
 Abualruz H.
 Abubakar U.
 Abukhadijah H.J.
 Aburuz S.
 Nauman J.
 Abu-Zaid A.
 Achalapong S.
 Khusuwan S.
 Ounchanum P.

Author's Affiliation

University North
 Research Center for Rational Use of Drugs
 Iranian Research Center for HIV/AIDS
 Mahidol Oxford Tropical Medicine Research Unit
 NIHR Oxford Biomedical Research Centre
 Research Center for Immunodeficiencies
 Non-Communicable Diseases Research Center
 University of Health and Allied Sciences, Ghana
 Alfaisal University
 Institute for Health Metrics and Evaluation
 Universidad de La Sabana
 Institut für Weltwirtschaft an der Universität Kiel
 Qatar University
 Hamad Medical Corporation
 College of Medicine and Health Sciences United Arab Emirates University
 Ajman University
 Kenya Medical Research Institute
 Al-Zaytoonah University of Jordan
 The University of Jordan
 Stanford University School of Medicine
 Universitetet i Bergen
 University of Washington School of Medicine
 Tehran University of Medical Sciences
 University of Texas Health Science Center at Houston
 University of Oxford
 Washington University School of Medicine in St. Louis
 University College London
 Shahid Beheshti University of Medical Sciences
 Thailand Ministry of Public Health
 University of Washington
 VA Medical Center
 Norges Teknisk-Naturvitenskapelige Universitet
 Karolinska Institutet
 Folkehelseinstituttet
 Instituto Nacional de la Nutrición Salvador Zubiran
 Nuffield Department of Medicine
 United Arab Emirates University
 Sina Trauma and Surgery Research Center
 University of Oxford Medical Sciences Division
 University of Tennessee Health Science Center
 Faculty of Medicine

Corresponding Author(s)

Naghavi M.

Other Contributor(s)

Mahidol University

Abstract

Background: Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts. Methods: We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen–drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level. Findings: In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000–372 000] and 57 200 attributable deaths [34 100–80 300] in 1990, to 550 000 associated deaths [500 000–600 000] and 130 000 attributable deaths [113 000–146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000–834 000) in 1990, to 1·03 million associated deaths (909 000–1·16 million) in 2021, and from 127 000 attributable deaths (82 100–171 000) in 1990, to 216 000 (168 000–264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56–2·26) deaths attributable to AMR and 8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2–69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5–89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (–6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8–102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08–13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths. Interpretation: This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050. Funding: UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/102371

Collections

Scopus 2024