A landmark GRAM Project study of global antimicrobial resistance (AMR) burden over time forecasts a sharp rise in deaths, with 39 million lives lost between now and 2050.
Resistance to antibiotics led to at least one million deaths each year since 1990, with increasing rates of drug-resistant infections expected to claim more than 39 million lives between now and 2050 without further policy action, according to a landmark study by the Global Research on Antimicrobial Resistance (GRAM) Project.
Published in the Lancet, 'Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050', is the first comprehensive analysis of antimicrobial resistance (AMR) trends over time. GRAM, a partnership between the Institute for Health Metrics and Evaluation (IHME) and Oxford, shows in the study that AMR has already claimed more than 36 million lives since 1990, with a death toll that is set to rise dramatically in future years.
Although annual deaths from AMR increased by about eight percent between 1990 and 2021, the study predicts a rise of almost 70 percent in the decades thereafter, with annual deaths rising from 1.14 million in 2021 to 1.91 million in 2050. A detailed forecast predicts that without further policy interventions global deaths would reach 39 million between 2025 and 2050-the equivalent of three deaths per minute.
The time series arrives as global health leaders meet later this month at the UN General Assembly in New York to consider new actions to combat AMR. At a high-level meeting on 26 September, officials will discuss interventions highlighted in the study-including infection prevention and control measures, such as new vaccines and antimicrobials, and improved access to water and sanitation-as well as deeper investments across health systems in diagnostics, training and new technologies.
Researchers also cited interventions to minimise inappropriate antibiotic use, and to encourage countries to complete their National Action Plans to address AMR. Failure to make progress on all front will cost lives, authors said.
'These findings highlight that AMR has been a significant global health threat for decades and that this threat is growing', said study author, Dr Mohsen Naghavi of IHME. 'Understanding how trends in AMR deaths have changed over time, and how they are likely to shift in future, is vital to make informed decisions to help save lives'.
A rising global challenge
Already widely recognised as a major global health challenge, AMR - which occurs when bacteria or other pathogens change in ways that make them no longer responsive to antimicrobials - is anticipated to worsen in the coming decades. However, until now, no studies have assessed historical trends of AMR and provided in-depth forecasts of future global impacts.
The first GRAM study, published in 2022, revealed the true scale of AMR for the first time. It found that global AMR-related deaths in 2019 were higher than those from HIV/AIDS or malaria, leading directly to 1.2 million deaths and playing a role in a further 4.95 million deaths. Read the study, 'Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis', in the Lancet.
In 2021, deaths attributable to AMR dropped slightly, to 1.14 million from 1.2 million in 2019-which followed from social distancing and other disease control measures in place during the COVID-19 pandemic, researchers said. GRAM's analysis suggests this decline in AMR deaths was only temporary.
For the time series, GRAM produced estimates for 22 pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes (including meningitis, bloodstream infections, and other infections) among people of all ages in 204 countries and territories. The estimates were based on 520 million individual records from a wide range of sources, including hospital data, death records, and antibiotic use data.
Based on the historical trends calculated, GRAM also forecasted the most likely global and regional health impacts of AMR from 2022 until 2050. Besides predicting the status quo, the forecast included two other scenarios, one that included stable development of new antibiotics, and one that included broad improvements in healthcare quality.
Researchers employed statistical models to produce estimates of deaths directly attributable to AMR, and those in which AMR played a role, so-called AMR-associated deaths.
Like attributable deaths, AMR-associated mortalities are also expected to increase. By 2050, AMR is also projected to play a role in 8.22 million AMR associated deaths - an increase of 75 percent from 4.71 million associated deaths in 2021. Between 2022 and 2050, GRAM forecasts 169 deaths associated with AMR.
Professor Dame Sally Davies, UK Special Envoy on AMR, said the devastating impact of drug resistance should spur action at next week's high-level meeting.
'This landmark study confirms that the world is facing an antibiotic emergency, with devastating human costs for families and communities across the world', Davies said. 'It substantiates our calls to all sectors to take decisive action now to save lives and save modern medicine for generations to come, and address the needs of low-and-middle income countries who bear the greatest tragedies from AMR'.
Key shifts
Deaths due to methicillin-resistant S. aureus (MRSA) increased most worldwide, leading directly to 130,000 deaths in 2021-more than doubling from 57,200 in 1990. Among Gram-negative bacteria-some of the most resistant to antimicrobial drugs-resistance to carbapenems increased more than any other type of antibiotic, from 127,000 in 1990 to 216,000 in 2021.
Between 1990 and 2021, AMR deaths among children under five years old declined by 50 percent. The study suggests this is owed to successes in reducing the incidence of serious childhood infections, such as through vaccination programmes including the roll-out of pneumococcal conjugate vaccines (PCV) and improved access to drinking water, sanitation and hygiene (WASH), and not by a reduction in the prevalence of AMR.
But deaths among people aged 70 years and older increased by more than 80 percent, due to rapidly ageing populations and older people's greater vulnerability to infection.
Researchers expect these trends to continue in the coming decades, with AMR deaths among children under five projected to halve by 2050 globally, as deaths among people 70 years and older more than double.
Deaths directly from AMR increased most in five global regions, where annual deaths rose by more than 10,000 between 1990 and 2021: western sub-Saharan Africa, Tropical Latin America, high-income North America, Southeast Asia, and South Asia.
Forecast impact
The latest GRAM estimates suggest that low- and middle-income countries will face a disproportionate burden.
Researchers forecast the highest level of AMR deaths in South Asia-including India, Pakistan, and Bangladesh-with a total of 11.8 million attributable AMR deaths between 2025 and 2050. GRAM also forecasts high rates of death in other parts of southern and eastern Asia and sub-Saharan Africa, with a particularly high number of deaths from multi-drug resistant (MDR) tuberculosis. (In-depth figures for specific regions are available in Table S17 in Appendix 1).
The forecasts also consider the potential impact of interventions on AMR deaths. The study suggests that the regular release of new antimicrobials targeting Gram-negative pathogens could avert up to 11 million AMR-related deaths, while deeper health investments, to improve care for severe infections and expand access to antibiotics, could save up to 92 million lives by 2050.
AMR in the GBD
GRAM's time series marks a key milestone for the project: inclusion of AMR in the Global Burden of Disease study. When global health leaders came together to create GRAM in 2017, they sought to make AMR measurable and comparable across other health threats-a key achievement of the GBD.
After many years of data collection and trial and error, AMR will now appear in regular iterations of the GBD.
But the authors acknowledged limitations in the study. A lack of data for some LMICs highlights a need for improved data collection - which requires investment in infrastructure - to strengthen estimates for these countries and improve the accuracy of future AMR forecasts. Some of the 520 million individual records used to produce the estimates may contain errors or biases, and limited reporting of AMR data before 2000 also may affect the strength of historical estimates in the 1990s.
Supporters hope the GRAM estimates will serve as a catalyst.
'While there has been some progress tackling AMR in recent years, it isn't enough and more needs to be done', said Dr Timothy Jinks, Head of Interventions in Wellcome Trust's Infectious Disease team. 'The GRAM estimates are an important tool in the fight against AMR, and we hope that global policymakers utilise the paper's findings to make evidence-based decisions… Implementation of bold action on AMR can strengthen health systems and protect the world's most vulnerable from infectious disease'.
