Antibiotic-resistant bacterial infections could take the lives of more than 39 million people by 2050 unless action is taken to improve healthcare quality, prevent infections, reduce inappropriate antibiotic use, and develop new antibiotics, according to a landmark new study published this week in The Lancet.
The modeling study by researchers with the Global Research on Antimicrobial Resistance (GRAM) Project forecasts, based on historical trends and the current trajectory of antimicrobial resistance (AMR), that more than a million people will die annually from 2025 to 2050 from an antibiotic-resistant infection, with an estimated 1.91 million dying in 2050. That represents an increase of almost 70% per year compared with 2021.
The study also estimates that annual deaths in which a drug-resistant infection plays a role but is not the direct cause (AMR-associated deaths) could rise to 8.22 million globally by 2050 -- a 75% increase from 2021. All told, the study forecasts that AMR could be associated with a cumulative 169 million deaths from 2025 to 2050.
The impact will vary by age, the researchers suggest, with AMR-attributable and -associated deaths nearly cut in half among children under the age of 5 years but increasing by 146% in people aged 70. Location will play a role as well, with countries in South and Southeastern Asia and sub-Saharan Africa seeing more AMR deaths than other parts of the world.
"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," the study authors warn.
For the study, an international team led by researchers at the University of Washington's Institute for Health Metrics and Evaluation (IHME) used the same methodology used in the first GRAM Project study, which was published in 2022. That study, which has become one of the most widely cited assessments of AMR-related mortality, estimated that 1.27 million global deaths in 2019 were directly attributable to AMR, out of a broader 4.95 million AMR-associated deaths.
But that was just 1 year. For this study, the team obtained 520 million individual records or bacterial isolates to first estimate deaths and disability-adjusted life years (DALYs) attributable to and associated with 22 bacterial pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes -- such as bloodstream infections, urinary tract infections, diarrhea, and meningitis -- in 204 countries from 1990 to 2021.
Using a variety of sources, including death records, insurance claims, published studies, hospital discharge data, microbiologic data, and antibiotic use surveys, the researchers calculated the AMR burden using an approach based on two counterfactual scenarios. To estimate deaths directly attributable to resistant bacteria, they considered a scenario in which those infections were replaced by antibiotic-susceptible infections. To estimate associated deaths, they considered a scenario in which resistant infections were replaced by no infection.
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.
For the 84 pathogen-drug combinations studied, the analysis found that global mortality from AMR increased from 1990 to 2021, with drug-resistant infections directly responsible for more than 1 million deaths each year and a cumulative total of more than 36 million deaths. Only 2021 saw a slight decrease in AMR-related deaths, likely because physical distancing, along with other disease control measures put into place during the COVID-19 pandemic, led to a reduction in non-COVID respiratory tract infections.
"This trend is consistent with everything we calculated in 2019," Mohsen Naghavi, PhD, MPH, leader of the AMR Research Team at IHME and a co-first author of the study, told CIDRAP News.
The biggest culprit behind AMR attributable deaths over the period was methicillin-resistant Staphylococcus aureus, which caused more than twice as many deaths in 2021 (130,000 attributable deaths) as in 1990 (57,200). Deaths caused by carbapenem-resistant gram-negative bacteria rose from 127,000 in 1990 to 216,000 in 2021. The regions that saw the biggest annual increases in AMR attributable deaths were West Africa, tropical Latin America, North America, Southeast Asia, and South Asia.
Over those three decades, however, AMR deaths declined by more than 50% among children 5 years old and younger, with AMR attributable deaths falling from 488,000 in 1990 to 193,000 in 2021. Deaths caused by drug-resistant Streptococcus pneumoniae, in particular, dropped dramatically in children under 5 -- from 158,000 in 1990 to 35,100 in 2021. There was also a significant reduction in pathogens commonly spread through the fecal-oral route, such as Shigella and Salmonella.
Naghavi, who's worked in public health for more than 50 years, attributes this decline to major improvements in infection prevention and control among infants and young children in low- and middle-income countries (LMICs), rather than a reduction in the prevalence of resistant pathogens.
"We did massive vaccination [campaigns], water and sanitation improvement, treatment of diarrhea with oral rehydration therapy, and massively better diagnosis and treatment for lower respiratory infections," he said. "That's why the number of deaths in children decreased."
By contrast, all age-groups 25 years and older saw an increase in AMR mortality, with older adults hit hardest. Adults over 70 years saw an 89% increase in attributable AMR deaths and an 81% increase in associated deaths from 1990 to 2021.
Study co-author Authia Gray, a post-bachelor fellow at IHME, explains that the AMR burden rose in older adults because they typically suffering from chronic illnesses, have more comorbidities, and are more susceptible to bacterial infections.
"We have a rapidly aging population in the global sphere [and] we have more old people that are more susceptible to infections," Gray said. "And then there's also other influential factors, such as older people are more likely to have adverse reactions to specific antibiotics, and are less likely to see high efficacy from treatments like vaccines."
The second part of the study -- the forecast of the future AMR burden -- predicts that those trends will continue from 2025 to 2050 based on the current trajectory. AMR-attributable deaths will further decline in children under 5, even as AMR spreads and more newborns face the threat of sepsis caused by multidrug-resistant bacteria.
"When children get infections today, they're actually more likely to have a resistant infection compared to the past," Gray said. "It's just that there are so fewer infections that it doesn't have as much of an impact."
Deaths from drug-resistant pathogens, however, will continue to climb in older adults as that increasingly vulnerable demographic group continues to grow and drives up antibiotic use, which will in turn increase the selection pressure for resistant bacteria.
We have a rapidly aging population in the global sphere [and] we have more old people that are more susceptible to infections.
But the forecast also presents some hope under two alternatives scenarios. One scenario envisions a healthy antibiotic pipeline that produces new and innovative drugs targeting the type of gram-negative bacterial pathogens that the World Health Organization has labeled "priority pathogens," such as carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Enterobacterales. Under this scenario, an estimated 11.1 million cumulative AMR-attributable deaths could be averted from 2025 to 2050.
In the "better care" scenario, an estimated 92 million cumulative AMR deaths could be averted through better care for severe infections and more widespread access to antibiotics. The biggest reductions would be seen in the regions where AMR is forecast to have the biggest impact, such as South Asia and sub-Saharan Africa.
"AMR will be with us forever...we cannot eradicate it," Naghavi said. "But if we provide an accessible, high-quality health system, we can limit AMR for everybody."
If those scenarios fail to materialize and no additional measures are taken, the authors say the goal a 10% reduction in AMR deaths by 2030 -- a target set by global AMR experts -- will be unachievable. That target will be among the topics of discussion at the upcoming United Nations General Assembly High-Level Meeting on AMR, held next week in New York.
...if we provide an accessible, high-quality health system, we can limit AMR for everybody.
Gray says she hopes their forecast will encourage governments and policy makers to address AMR in global and national action plans, put more money into vaccines and other tools that can prevent infections, and ensure that those tools are available in the LMICs that are most affected by AMR.
"There's gross inequity in terms of how AMR is treated throughout the world," she said.
In an accompanying commentary, Samuel Kariuki, PhD, of the Kenya Medical Research Institute, says that while the model is limited by scarcity of data in many LMICs and doesn't account for the potential emergence of new superbugs, it provides a clearer understanding of how the burden of AMR is developing and could help policy makers around the world make more informed decisions about interventions.
"Having data on the trends of the burden of AMR and the prediction of this burden in the coming three decades provides additional motivation for effective intervention measures by all stakeholders," Kariuki wrote. "These data should drive investments and targeted action towards addressing the growing challenge of AMR in all regions."