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

 

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

 

It reveals that more than one million people died each year as a result of AMR between 1990 and 2021. The study also estimates 1.91 million people could potentially die as a direct result of AMR in 2050, an increase of almost 70% 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% from 4.71 million to 8.22 million per year.

 

Between 1990 and 2021, AMR deaths among children under five years old declined by 50%, while those among people aged 70 years and older increased by more than 80%. These trends are 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 highlight a vital need for interventions that incorporate infection prevention, vaccination, minimizing inappropriate antibiotic use, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050.

 

"Antimicrobial medicines are one of the cornerstones of modern health care, 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," said study author Dr. Mohsen Naghavi, Team Leader of the AMR Research Team at the Institute of Health Metrics (IHME), University of Washington, U.S.

 

Already widely recognized as a major global health challenge, AMR—which occurs when bacteria or other pathogens change in ways that make them evolve to no longer respond 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.

 

Estimates for the new 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 520 million individual records from a wide range of sources, including hospital data, death records, and antibiotic use data.

 

Statistical modeling 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 estimate the most likely global and regional health impacts of AMR from 2022 until 2050.

 

Estimates were also produced for scenarios in which health care quality and access to antibiotics improve in the future and drug development targets Gram-negative bacteria.

 

Shifting global trends

 

Their findings reveal that more than one million lives were lost each year from 1990 to 2021 as a direct result of AMR. In 1990, there were 1.06 million deaths directly due to AMR of a broader 4.78 million associated deaths. In 2021, AMR led directly to 1.14 million deaths and was associated of a broader 4.71 million deaths.

 

AMR deaths in 2021 were lower than in 2019 (1.27 million direct AMR deaths; 4.95 million 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 suggests 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% (59.8% reduction in direct AMR deaths, 488,000 to 193,000 deaths; 62.9% reduction in deaths linked to AMR, 2.29 million to 840,00 deaths).

 

This decline coincided with major improvements in the delivery of infection prevention and control measures—such as vaccination programs—among infants and young children. However, the proportion of infectious deaths caused directly by AMR increased by a relative 13.6%—to a total of 7.2% 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% (89.7% increase in direct AMR deaths, 519,000 in 2021; 81.4% increase in deaths linked to AMR, 2.16 million in 2021), due to rapidly aging populations and older people's greater vulnerability to infection.

 

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.

 

"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," said study author Dr. Kevin Ikuta of the University of California Los Angeles (UCLA) and affiliate professor at IHME.

 

Different pathogens

 

The findings reveal increasing resistance to critically important antimicrobials, with all but one of seven key pathogens rated by the WHO 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—worst can be averted by action now

 

The authors estimate that AMR deaths will increase steadily in the coming decades based on current trends, with 1.91 million annual deaths directly due to AMR projected by 2050—a 67.5% increase on the 1.14 million deaths in 2021. By the middle of the century, AMR is also projected to play a role in a broader 8.22 million deaths—an increase of 74.5% on the 4.71 million 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 169 million deaths.

 

Deaths among children under five years old will continue to decline, halving in 2050 compared to 2022 (49.6% 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% increase by 2050, from 512,353 to 1,259,409).

 

There will be considerable differences globally, with a 72% increase in deaths among people 70 years and older in high-income countries compared to a 234% increase in North Africa and the Middle East.

 

Future deaths from AMR will be highest in South Asia—which includes countries such as India, Pakistan, and Bangladesh—where a total of 11.8 million deaths directly due to AMR are forecast between 2025 and 2050. Deaths from AMR will also be high in other parts of southern and eastern Asia and sub-Saharan Africa.

 

The team's modeling of alternative future scenarios reveals improving overall infection care and access to antibiotics could prevent 92 million deaths between 2025 and 2050. The greatest benefits would be in South Asia, sub-Saharan Africa, and parts of Southeast Asia, East Asia, and Oceania, with 31.7 million, 25.2 million, and 18.7 million deaths averted, respectively.

 

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

 

"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 8 million deaths each year, either as the direct cause of death or as a contributing factor," said study author Dr. Stein Emil Vollset of the Norwegian Institute of Public Health and affiliate professor at IHME.

 

"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 health care, better access to existing antibiotics, and guidance on how to use them most effectively."

 

The authors acknowledge some limitations to their 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. There was also limited reporting of AMR data before 2000, which may affect the strength of historical estimates in the 1990s.

 

Writing in a linked Comment, Professor Samuel Kariuki, of the Kenya Medical Research Institute, who was not involved in the study, said, "The model successfully evaluated the changing trends in AMR mortality across time and location that is necessary to understand how the burden of AMR is developing, and to provide evidence for action by all stakeholders to make informed decisions regarding interventions."

 

Professor Kariuki concludes, "These data should drive investments and targeted action towards addressing the growing challenge of AMR in all regions."