Peer-reviewed / Observational and modelling study / People
- First comprehensive analysis of global impact of antimicrobial resistance (AMR) estimates resistance itself caused 1.27 million deaths in 2019, and that antimicrobial-resistant infections played a role in 4.95 million deaths.
- Estimates for 204 countries and territories confirm AMR as a global health threat, with worst impacts in low- and middle-income countries (LMICs), though higher income countries also face alarmingly high levels of AMR.
- Rapid investment in new treatments, improved infection control measures, and optimised use of antibiotics are among the measures that can help countries protect their health systems against the threat of AMR.
More than 1.2 million people – and potentially millions more – died in 2019 as a direct result of antibiotic-resistant bacterial infections, according to the most comprehensive estimate to date of the global impact of antimicrobial resistance (AMR).
The analysis of 204 countries and territories, published in The Lancet, reveals that AMR is now a leading cause of death worldwide, higher than HIV/AIDS or malaria. It shows that many hundreds of thousands of deaths now occur due to common, previously treatable infections – such as lower respiratory and bloodstream infections – because the bacteria that cause them have become resistant to treatment.
The report highlights an urgent need to scale up action to combat AMR, and outlines immediate actions for policymakers that will help save lives and protect health systems. These include optimising the use of existing antibiotics, taking greater action to monitor and control infections, and providing more funding to develop new antibiotics and treatments.
Study co-author Professor Chris Murray, of the Institute for Health Metrics and Evaluation at the University of Washington, USA, said: “These new data reveal the true scale of antimicrobial resistance worldwide, and are a clear signal that we must act now to combat the threat. Previous estimates had predicted 10 million annual deaths from antimicrobial resistance by 2050, but we now know for certain that we are already far closer to that figure than we thought. We need to leverage this data to course-correct action and drive innovation if we want to stay ahead in the race against antimicrobial resistance.” 
Estimates of the health impacts of AMR have been published for several countries and regions, and for a small number of pathogen-drug combinations in a wider range of locations. However, until now no estimates have covered all locations and a broad range of pathogens and drug combinations.
The new Global Research on Antimicrobial Resistance (GRAM) report estimates deaths linked to 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. Statistical modelling was used to produce estimates of the impact of AMR in all locations – including those with no data – using 471 million individual records obtained from systematic literature reviews, hospital systems, surveillance systems, and other data sources.
Disease burden was estimated in two ways: deaths caused directly by AMR (i.e. deaths that would not have occurred had the infections been drug-susceptible and therefore more treatable), and deaths associated with AMR (i.e. where a drug-resistant infection was implicated in deaths, but resistance itself may or may not have been the direct cause). Deaths caused by and associated with AMR were calculated for 204 countries and territories and reported for 21 global regions and seven super-regions.
The analysis shows AMR was directly responsible for an estimated 1.27 million deaths worldwide, and associated with an estimated 4.95 million deaths, in 2019. HIV/AIDS and malaria have been estimated to have caused 860,000 and 640,000 deaths, respectively, in 2019. 
Drug-resistance in lower respiratory infections – such as pneumonia – had the greatest impact on AMR disease burden, causing more than 400,000 deaths and associated with more than 1.5 million deaths. Drug resistance in bloodstream infections – which can lead to the life-threatening condition sepsis – caused around 370,000 deaths and was associated with nearly 1.5 million deaths. Drug resistance in intra-abdominal infections – commonly caused by appendicitis – led directly to around 210,000 deaths and was associated with around 800,000.
While AMR poses a threat to people of all ages, young children were found to be at particularly high risk, with around one in five deaths attributable to AMR occurring in children aged under five years.
Deaths caused directly by AMR were estimated to be highest in Sub-Saharan Africa and South Asia, at 24 deaths per 100,000 population and 22 deaths per 100,000 population, respectively. AMR was associated with 99 deaths per 100,000 in Sub-Saharan Africa and 77 deaths per 100,000 in South Asia. In high-income countries, AMR led directly to 13 deaths per 100,000 and was associated with 56 deaths per 100,000. (For regional data, see Table 3 in the paper).
Of the 23 pathogens studied, drug resistance in six alone (E. coli, S. aureus, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa) led directly to 929,000 deaths and was associated with 3.57 million. One pathogen-drug combination – methicillin-resistant S. aureus, or MRSA – directly caused more than 100,000 deaths in 2019, while six more each caused between 50,000 and 100,000 deaths.
Across all pathogens, resistance to two classes of antibiotics often considered the first line defence against severe infections – fluoroquinolones and beta-lactam antibiotics – accounted for more than an estimated 70% of deaths caused by AMR.
The health impact of pathogens varied widely based on location, with deaths attributable to AMR in Sub-Saharan Africa most often caused by S. pneumonia (16% of deaths) or K. pneumonia (20%), while around half of deaths attributable to AMR in high-income countries were caused by S. aureus (26%) or E. coli (23%).
“With resistance varying so substantially by country and region, improving the collection of data worldwide is essential to help us better track levels of resistance and equip clinicians and policymakers with the information they need to address the most pressing challenges posed by antimicrobial resistance. We identified serious data gaps in many low-income countries, emphasising a particular need to increase laboratory capacity and data collection in these locations,” said study co-author Prof Christiane Dolecek, GRAM scientific lead based in Oxford University’s Centre for Tropical Medicine and Global Health and the Mahidol Oxford Tropical Medicine Research Unit (MORU). 
The authors acknowledge some limitations to their study. Limited availability of data for some parts of the world, particularly many LMICs, may limit the accuracy of estimates in these locations as this required strong methodological assumptions to be made in the analysis. Combining and standardising data from a wide variety of sources also led to some potential sources of bias, including misclassification of community- or hospital-acquired infections, and inconsistency in the distinction between drug resistant and susceptible infections. There is also the potential for selection bias in passive surveillance systems, and hospital microbial data from LMICs may skew towards more urban populations or more severe disease.
Writing in a linked Comment, Dr Ramanan Laxminarayan, Center for Disease Dynamics, Economics & Policy (USA), who was not involved in the study, said: "From being an unrecognised and hidden problem, a clearer picture of the burden of AMR is finally emerging. Even the lower end of 911,000 deaths estimated by Murray and colleagues is higher than the number of deaths from HIV, which attracts close to US$50 billion each year. However, global spending on addressing AMR is probably much lower than that. This needs to change. Spending needs to be directed to preventing infections in the first place, making sure existing antibiotics are used appropriately and judiciously, and to bringing new antibiotics to market. Health and political leaders at local, national, and international levels need to take seriously the importance of addressing AMR and the challenge of poor access to affordable, effective antibiotics."
NOTES TO EDITORS
This study was funded by the Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund. A full list of the AMR Collaborators involved in the study is available at the end of the manuscript.
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Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis
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E Ashley reports that Lao-Oxford-Mahosot Hospital—Wellcome Trust Research Unit received financial support from the Global Research on Antimicrobial Resistance Project (GRAM) to extract and prepare data for the present manuscript. J Bielicki reports grants from the European and Developing Countries Clinical Trials Partnership, Horizon 2020, and Swiss National Science Foundation, and a contract from the National Institute for Health Research (NIHR), outside of the submitted work; and consulting fees from Shionogi and Sandoz and speaking fees from Pfizer and Sandoz, outside the submitted work. C Carvalheiro reports financial support for the present manuscript from the Global Antibiotic Research and Development Partnership, who provided payments to Fundação de Apoio ao Ensino, Pesquisa e Assistência of the Clinical Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. S Dunachie reports financial support for the present manuscript from UL Flemming Fund at the Department of Health and Social Care, the Bill & Melinda Gates Foundation, and the Wellcome Trust; a paid membership role for the Wellcome Trust Vaccines Advisory Selection Panel Vaccines and AMR in November, 2019; and an unpaid role as an expert adviser to WHO’s Global Antimicrobrial Resistance Surveillance System, from November, 2018 onwards, outside the submitted work. A Haselbeck reports support for the present manuscript from the Bill & Melinda Gates Foundation (OPP1205877). C Lim was supported by the Wellcome Trust Training Fellowship between September, 2017 and March 2020 (206736/Z/17/Z), outside the submitted work. M Mussi-Pinhata reports support for the present manuscript from research from grant funding from Fondazione PENTA—Onlus and the Clinical Trial Manager Global Antibiotic R&D Partnership (GARDP). P Newton reports support for the present manuscript from research grant funding from the Wellcome Trust. J Robotham is a member of the UK Government Advisory Committee on Antimicrobial Prescribing Resistance and Healthcare Associated Infections, outside the submitted work. J Scott reports that the London School of Hygiene & Tropical Medicine (LSHTM) received financial support from Emory University to support CHAMPS projects in Ethiopia for the present manuscript; reports a paid fellowship from the Wellcome Trust, research grants from Gavi, the Vaccine Alliance, and NIHR paid to LSHTM, and an African research leader fellowship paid to LSHTM by the Medical Research Council, outside the submitted work; and reports being a member of the data safety and monitoring board for PATH Vaccines Solutions for SII PCV10 in The Gambia. J Sifuentes-Osornio reports financial support from Oxford University for the present manuscript; research grants from Oxford, CONACYT, Sanofi, and Novartis, outside of the study; consulting fees from Senosiain and speaker fees from Merck, outside of the study; and membership of the Sanofi advisory board of COVID-19 Vaccine Development, which is currently in progress, outside of the study. A J Stewardson reports grants or contracts from Merck, Sharp, & Dohme paid to Monash University, Melbourne, outside of the study. P Turner reports grants, consulting fees, and support for attending meetings or travel from Wellcome Trust, outside the study. H van Doorn reports grants or contracts from the University of Oxford and is the principal investigator for the Fleming Fund pilot grant; and he is a board member of Wellcome Trust’s Surveillance and Epidemiology of Drug Resistant Infections. T Walsh reports financial support from the Bill & Melinda Gates Foundation for the BARNARDS (neonatal sepsis and mortality) study for the present manuscript. All other authors declare no competing interests.