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Need for New Efforts From Global Health Policy Makers to Address the Burden of Antimicrobial Resistance
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050
Lancet 2024 Sep 28;404(10459)1199-1226, GBD 2021 Antimicrobial Resistance CollaboratorsFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Policymakers used the 2014 Review on Antimicrobial Resistance (AMR) to identify national and global goals (Sustainable Development Goal 3.d.2), create strategies to improve patient safety, and outline evidence-based treatments that could reduce the burden and risk associated with AMR.
A decade later, researchers updated the AMR global estimates using a 10-step methodology rooted in data and analyses that were previously validated. The research team provides current and projected estimates for the AMR burden associated with 11 syndromes, 22 bacterial pathogens, 16 drug categories for which there is resistance, and 84 pathogen–drug combinations. They analyzed input data across multiple networks and reviewed 520 million individual records covering 19,513 study-location-years.
Key outcomes aggregated to the global, super-regional, and regional level include:
Challenges in conducting research to generate estimates and forecasting include biases, misclassifications, validity of data inputs and algorithms, and limitations of historical estimates. However, the researchers in this article have made every attempt to minimize these limitations and strengthen the accuracy of these estimates.
What does this article mean for the clinician?
It is going to take all of us practicing infection prevention and antibiotic stewardship and collaborating to build new treatments for all infections.
What does this article mean for the politician?
It is going to take all of us globally to support the implementation of health systems infrastructure, integrate AMR surveillance to include food safety and animal health, as well as account for environmental residues of antibiotics and pesticide use, and financially support the development of innovative healthcare modalities for infections.
What does this article mean for a family?
It is going to take all of us to ensure our children are vaccinated, antibiotics are used only when necessary for humans and animals, and all leftover antibiotics are disposed of properly.
Together, we can achieve the best-case scenario for 2050.