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Antimicrobial-resistant bacterial infections directly caused more than 1 million deaths worldwide annually from 1990 to 2021, and that number is projected to increase by almost 70% over the next 25 years, according to a systematic analysis.

In 2021, 1.14 million deaths that were attributable to bacterial antimicrobial resistance (AMR) occurred across the globe, slightly higher than the 1.06 million AMR-attributable deaths in 1990, reported Christopher Murray, MD, DPhil, of the University of Washington in Seattle, and colleagues in

Bacterial AMR was also associated with an estimated 4.71 million deaths in 2021, about the same as in 1990.

By 2050, Murray and colleagues forecasted that an estimated 1.91 million AMR-attributable deaths and 8.22 million AMR-associated deaths could occur every year worldwide. From 2025 to 2050, a cumulative 39.1 million deaths attributable to AMR could occur.

However, improved access to healthcare and antibiotics could save an estimated 92 million lives from 2025 to 2050, they posited.

"These findings highlight that AMR has been a significant global health threat for decades and that this threat is growing," co-author Mohsen Naghavi, MD, PhD, MPH, also of the University of Washington, commented in a.

On a more positive note, AMR-attributable deaths among children under the age of 5 years decreased by 60.4% from 1990 to 2021, and deaths associated with AMR decreased by 63.3%. Sepsis deaths among children younger than 5 also decreased by more than 60% over this time period.

However, among people 70 and older, deaths directly attributable to AMR increased by 89.5%, and AMR-associated deaths increased by 81.3%, from 1990 to 2021.

"The fall in deaths from sepsis and AMR among young children over the past three decades is an incredible achievement," co-author Kevin Ikuta, MD, MPH, of the University of California Los Angeles, said in the press release.

"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," Ikuta pointed out.

In an , Samuel Kariuki, PhD, MSc, of the Kenya Medical Research Institute in Nairobi, noted that the reduction in deaths among young children "coincides with widespread vaccination efforts and improved access to WASH [water, sanitation, and hygiene], and infection prevention and control strategies that proved highly effective in reducing AMR burden."

Improved access to WASH infrastructure and practice coupled with use of pediatric vaccines could prevent approximately 430,000 AMR-associated deaths, "from both direct prevention of resistant infections and reductions in antibiotic consumption," Kariuki wrote.

In their predictions for 2050, Murray and colleagues projected that South Asia, Latin America, and the Caribbean will be the regions with the highest all-age AMR mortality rate. Increases in deaths attributable to AMR will be largest among those 70 and older (65.9%).

However, improved access to antibiotics and better care could have the greatest benefits in South Asia, sub-Saharan Africa, and parts of Southeast Asia, East Asia, and Oceania, they noted.

The researchers also documented increases in AMR-attributable deaths for 12 pathogens from 1990 to 2021. In 2021, the six pathogens associated with at least 100,000 AMR-attributable deaths annually were Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, and Pseudomonas aeruginosa.

Deaths due to methicillin-resistant S. aureus increased the most globally, leading to 130,000 AMR-attributable deaths in 2021 -- doubling from 57,200 in 1990.

Among Gram-negative bacteria, which are 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. "If new antimicrobials are developed for currently antimicrobial-resistant Gram-negative bacteria, a forecasted 11.1 million AMR deaths could be averted by 2050," Kariuki noted.

S. pneumoniae had the most substantial decline in both AMR-associated and -attributable deaths, with AMR-attributable deaths dropping from 258,000 in 1990 to 155,000 in 2021.

Deaths attributable to AMR also varied across regions. Five regions -- western sub-Saharan Africa, tropical Latin America, high-income North America, Southeast Asia, and South Asia -- had increases of more than 10,000 AMR-attributable deaths over the 31-year period. However, among children younger than 5 years, AMR-attributable and -associated deaths decreased in all regions except Oceania. Among those ages 5 and older, AMR mortality increased in all regions except western and central Europe.

This global study relied on a statistical modeling approach using 520 million individual records from a variety of sources, including hospital data, death records, antibiotic use surveys, pharmaceutical sales data, insurance claims data, and published scientific studies, among others. Murray and colleagues looked at 22 pathogens, 84 pathogen-drug combinations, and 11 infectious syndromes from 204 countries and territories.

The authors acknowledged some limitations to the analysis. Scarcity of data in many low- to middle-income countries was a major drawback. Also, analytical errors and selection bias may have occurred when consolidating data from a large variety of sources. Forecast scenarios of AMR burden are also dependent on the quality and availability of historical data, and do not consider the emergence of new resistant strains of bacteria.

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