More than 39m people around the world could die from antibiotic-resistant infections over the next 25 years, according to a study published in The Lancet.

The study by the Global Research on Antimicrobial Resistance (GRAM) Project is the first global analysis of antimicrobial resistance (AMR) trends over time.

It revealed that between 1990 and 2021, more than one million people died each year because of AMR.

The study estimates that 1.91m people could potentially die as a direct result of AMR in 2050, an increase of almost 70 per cent per year compared to 2022. Over the same period, the number of deaths in which AMR bacteria play a role will increase by almost 75 per cent from 4.71m to 8.22m per year.

Between 1990 and 2021, AMR deaths among children under five years old declined by 50 per cent, while those among people aged 70 years and older increased by more than 80 per cent. These trends have been predicted 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.

The findings have highlighted a vital need for interventions that incorporate infection prevention, vaccination, minimising inappropriate antibiotic use, and research into new antibiotics to mitigate the number of AMR deaths that have been forecast for 2050.

Mohsen Naghavi, study author and team leader of the AMR research team at the Institute of Health Metrics (IHME), University of Washington, 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. 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.”

The global crisis

AMR is recognised as a major global health challenge. It occurs when bacteria or other pathogens change in ways that make them evolve to no longer respond to antimicrobials. This is anticipated to worsen in the coming decades.

According to researchers, 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 1.2m deaths and playing a role in a further 4.95m deaths.

Estimates for the latest GRAM study were produced 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 520m individual records from various sources, including hospital data, death records, and antibiotic use data.

Statistical modelling was used to produce estimates of deaths directly from AMR and those in which AMR played a role. Based on the historical trends calculated, the authors estimated AMR's most likely global and regional health impacts from 2022 until 2050. Estimates were also produced for scenarios in which healthcare quality and access to antibiotics improve in the future and drug development targets gram-negative bacteria.

Shifting trends

The findings have revealed that more than one million lives were lost each year from 1990 to 2021 as a direct result of AMR:

  • In 1990, there were 1.06m deaths directly due to AMR of a broader 4.78m associated deaths.
  • In 2021, AMR led directly to 1.14m deaths and was associated of a broader 4.71m deaths.

AMR deaths in 2021 were lower than in 2019 (1.27m direct AMR deaths; 4.95m associated deaths) due to reductions in the burden of non-covid lower respiratory infections, likely caused by social distancing and other disease control measures in place during the Covid-19 pandemic.

The team’s analysis suggested that this decline in AMR deaths was only temporary.

Over the three decades, trends in AMR deaths underwent a major age-related shift, with those among children under five years old decreasing by more than 50 per cent (59.8 per cent reduction in direct AMR deaths, 488,000 to 193,000 deaths; 62.9 per cent reduction in deaths linked to AMR, 2.29m to 840,00 deaths).

This decline coincided with major improvements in the delivery of infection prevention and control measures, such as vaccination programmes, among infants and young children. However, the proportion of infectious deaths caused directly by AMR increased by a relative 13.6 per cent (to a total of 7.2 per cent in 2021) among children under five years between 1990 and 2021.

Over the same period, AMR deaths among adults 70 years or older increased by more than 80 per cent (89.7 per cent increase in direct AMR deaths, 519,000 in 2021; 81.4 per cent increase in deaths linked to AMR, 2.16m in 2021), due to a rapidly ageing populations and older people’s greater vulnerability to infection.

Kevin Ikuta, study author and a professor at the University of California Los Angeles (UCLA), said, “The fall in deaths from sepsis and AMR among young children over the past three decades is an incredible achievement. However, these findings show that while infections have become less common in young children, they have become harder to treat when they occur. Further, the threat to older people from AMR will only increase as populations age. Now is the time to act to protect people around the world from the threat posed by AMR.”

Different pathogens

The findings have revealed an increasing resistance to critically important antimicrobials, with all but one of seven key pathogens rated by the World Health Organisation as the most difficult to treat, leading to more deaths in 2022 compared to 1990.

Deaths due to methicillin-resistant S. aureus (MRSA) increased the most globally, 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.

Future projections

The authors estimate that AMR deaths will increase steadily in the coming decades based on current trends, with 1.91m annual deaths directly due to AMR projected by 2050 – a 67.5 per cent increase on the 1.14m deaths in 2021. By the middle of the century, AMR is also projected to play a role in a broader 8.22m deaths – an increase of 74.5 per cent on the 4.71m associated deaths in 2021.

In total, between 2025 and 2050, it is estimated AMR will lead directly to more than 39 million deaths and be associated with a broader 169m deaths.

Deaths among children under five years old will continue to decline, halving in 2050 compared to 2022 (49.6 per cent decline, 204,000 to 103,000 deaths), but these will be outpaced by increases in other age groups, particularly those aged 70 years and older (146 per cent increase by 2050, from 512,353 to 1,259,409). There will be considerable differences globally, with a 72 per cent increase in deaths among people 70 years and older in high-income countries compared to a 234 per cent increase in North Africa and the Middle East.

The team’s modelling of alternative future scenarios reveals improving overall infection care and access to antibiotics could prevent 92m deaths between 2025 and 2050.

Under the scenario in which new antibiotics targeting gram-negative bacteria were developed, estimates indicate 11.08m AMR-attributable deaths could be averted globally over the same period.

Stein Emil Vollset, study author and a professor at the Norwegian Institute of Public Health, said, “There has been real progress in tackling AMR, particularly among young children, but our findings indicate more must be done to protect people from this growing global health threat. By 2050, resistant infections could be involved in some eight million deaths each year, either as the direct cause of death or as a contributing factor.

“To prevent this from becoming a deadly reality, we urgently need new strategies to decrease the risk of severe infections through vaccines, new drugs, improved healthcare, better access to existing antibiotics, and guidance on how to use them most effectively.”

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