EduCation on Antimicrobial REsistance for the health workforce(AMR-EDUcare)
Antimicrobial resistance (AMR) poses an important global health challenge in the 21st
century. A previous study has quantified the global and regional burden of AMR for
2019, followed with additional publications that provided more detailed estimates
for several WHO regions by country. To date, there have been no studies that produce
comprehensive estimates of AMR burden across locations that encompass historical trends
and future forecasts.We estimated all-age and age-specific deaths and disability-adjusted
life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens,
84 pathogen-drug combinations, and 11 infectious syndromes in 204 countries and territories
from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge
data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical
sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and
inpatient insurance claims data, and previously published data, covering 520 million
individual records or isolates and 19 513 study-location-years. We used statistical
modelling to produce estimates of AMR burden for all locations, including those with
no data. Our approach leverages the estimation of five broad component quantities:
the number of deaths involving sepsis; the proportion of infectious deaths attributable
to a given infectious syndrome; the proportion of infectious syndrome deaths attributable
to a given pathogen; the percentage of a given pathogen resistant to an antibiotic
of interest; and the excess risk of death or duration of an infection associated with
this resistance. Using these components, we estimated disease burden attributable
to and associated with AMR, which we define based on two counterfactuals; respectively,
an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible
infections, and an alternative scenario in which all drug-resistant infections were
replaced by no infection. Additionally, we produced global and regional forecasts
of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic
forecast of the most likely future; a Gram-negative drug scenario that assumes future
drug development that targets Gram-negative pathogens; and a better care scenario
that assumes future improvements in health-care quality and access to appropriate
antimicrobials. We present final estimates aggregated to the global, super-regional,
and regional level.In 2021, we estimated 4·71 million (95% UI 4·23-5·19) deaths were
associated with bacterial AMR, including 1·14 million (1·00-1·28) deaths attributable
to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially
by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50%
among children younger than 5 years yet increased by over 80% for adults 70 years
and older. AMR mortality decreased for children younger than 5 years in all super-regions,
whereas AMR mortality in people 5 years and older increased in all super-regions.
For both deaths associated with and deaths attributable to AMR, meticillin-resistant
Staphylococcus aureus increased the most globally (from 261 000 associated deaths
[95% UI 150 000-372 000] and 57 200 attributable deaths [34 100-80 300] in 1990, to
550 000 associated deaths [500 000-600 000] and 130 000 attributable deaths [113 000-146
000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more
than any other antibiotic class, rising from 619 000 associated deaths (405 000-834
000) in 1990, to 1·03 million associated deaths (909 000-1·16 million) in 2021, and
from 127 000 attributable deaths (82 100-171 000) in 1990, to 216 000 (168 000-264
000) attributable deaths in 2021. There was a notable decrease in non-COVID-related
infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million
(1·56-2·26) deaths attributable to AMR and 8·22 million (6·85-9·65) deaths associated
with AMR could occur globally in 2050. Super-regions with the highest all-age AMR
mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean.
Increases in deaths attributable to AMR will be largest among those 70 years and older
(65·9% [61·2-69·8] of all-age deaths attributable to AMR in 2050). In stark contrast
to the strong increase in number of deaths due to AMR of 69·6% (51·5-89·2) from 2022
to 2050, the number of DALYs showed a much smaller increase of 9·4% (-6·9 to 29·0)
to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all
age groups, 92·0 million deaths (82·8-102·0) could be cumulatively averted between
2025 and 2050, through better care of severe infections and improved access to antibiotics,
and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08-13·2) could
be averted through the development of a Gram-negative drug pipeline to prevent AMR
deaths.This study presents the first comprehensive assessment of the global burden
of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing
trends in AMR mortality across time and location is necessary to understand how this
important global health threat is developing and prepares us to make informed decisions
regarding interventions. Our findings show the importance of infection prevention,
as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously,
our results underscore the concerning trend of AMR burden among those older than 70
years, alongside a rapidly ageing global community. The opposing trends in the burden
of AMR deaths between younger and older individuals explains the moderate future increase
in global number of DALYs versus number of deaths. 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.UK Department of Health and Social Care's Fleming Fund using UK aid, and
the Wellcome Trust.
