In a chilling prediction, a new global analysis estimates that “superbugs” will kill more than 39m people before 2050, with older people particularly at risk as evolving bacteria become increasingly resistant to drugs.
Researchers said deaths linked to drug resistance are declining among very young children, driven by improvements in vaccination and hygiene, but they found the opposite trend for their grandparents.
By the middle of the century, 1.91m people a year are forecast to die worldwide directly because of antimicrobial resistance (AMR) – in which bacteria evolve so that the drugs usually used to fight them no longer work – up from 1.14mi in 2021. AMR will play some role in 8.2m deaths annually, up from 4.71m.
The study, published in The Lancet, was conducted by the Global Research on Antimicrobial Resistance (Gram) Project and is the first global analysis of AMR trends over time, reports The Guardian.
The researchers used data from 204 countries and territories to produce estimates of deaths from 1990 to 2021, and forecasts running through to 2050.
They also found millions of deaths worldwide could be averted via better prevention of infections and improved access to healthcare, as well as the creation of new antibiotics.
The study’s author, Dr Mohsen Naghavi, at the University of Washington’s Institute of Health Metrics (IHME), said: “Antimicrobial medicines are one of the cornerstones of modern healthcare, and increasing resistance to them is a major cause for concern.
“These findings highlight that AMR has been a significant global health threat for decades and that this threat is growing.”
Global leaders will meet in New York this month to discuss antimicrobial resistance, during the UN’s general assembly. They are expected to reaffirm a political declaration on stepping up action against antimicrobial resistance, which campaigners hope will include a target to reduce AMR deaths by 10% by 2030.
The study, which involved more than 500 researchers from institutions worldwide, found a “remarkable” decline in AMR deaths among children under five – from 488 000 to 193 000 – between 1990 and 2022. They are expected to halve again by 2050.
However, while deaths due to infection in young children are fewer in number, they are increasingly likely to be caused by drug-resistant bacteria.
And death tolls are rising in all other age groups, with AMR fatalities among the over-70s already up 80% in three decades and expected to rise 146% by 2050, from 512 353 to 1.3m.
CNN reports that the researchers found that from 1990 to 2021, deaths from AMR fell more than 50% among children younger than five but increased more than 80% among adults 70 and older – trends that are forecast to continue.
It was surprising to see those patterns emerge, “we expect it to get worse,” said lead author Dr Chris Murray, director of the Institute for Health Metrics and Evaluation at the University of Washington.
“We had these two opposite trends going on: a decline in AMR deaths under age 15, mostly due to vaccination, water and sanitation programmes, some treatment programs, and the success of those,” Murray said.
“And at the same time, there’s this steady increase in the number of deaths over age 50,” he said, as the world ages; older adults can be more susceptible to severe infection.
The researchers found that the pathogen-drug combination that had the largest increase in causing the most burden among all age groups was methicillin-resistant Staphylococcus aureus, or MRSA. For this combination – the antibiotic methicillin and the bacteria S. aureus – the number of attributable deaths nearly doubled from 57 200 in 1990 to 130 000 in 2021.
About 520m individual records were part of the data to make those estimates.The researchers found that the pathogen-drug combination that had the largest increase in causing the most burden among all age groups was methicillin-resistant Staphylococcus aureus, or MRSA. For this combination – the antibiotic methicillin and the bacteria S. aureus – the number of attributable deaths nearly doubled from 57 200 in 1990 to 130 000 in 2021.
Dr Tomislav Meštrović, assistant professor at University North in Croatia and an affiliate associate professor at the IHME, said the trend reflected rapidly ageing populations, with older people more vulnerable to infection.
“Approximately three-quarters of AMR infections are linked, for example, to hospital infections, and a rapidly ageing population also necessitates more hospital care,” he said. Older people have more chronic diseases, like diabetes and heart disease.
“For example, you put in an IV line, it gets infected, you get bacteria in the blood, that bacteria is likely to be more resistant,” he said.
Vaccination was often less effective in older people because the immune system deteriorated with age, he added, and older people were more prone to have reactions to antibiotics.
AMR deaths in 2021 were lower than in 2019, but the researchers said this was likely to be only a temporary reduction due to fewer infections because of Covid-19 control measures.
The study projected that the highest numbers of future deaths would occur in South Asian countries like India, Pakistan and Bangladesh, as well as other parts of southern and eastern Asia and sub-Saharan Africa.
They are among areas that have already seen the highest growth in AMR, and could also see some of the greatest benefits from improving overall infection care and widening access to antibiotics.
Study details
Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050
GBD 2021 Antimicrobial Resistance Collaborators
Published in The Lancet on 16 September 2024
Summary
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.
CNN – Superbug crisis could get worse, killing nearly 40 million people by 2050, study estimates
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