Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Continued overuse of antimicrobials, both in human health and in agriculture, produces an environment that selects for increasingly resistant bacteria.

“Furthermore, the continued overuse of antimicrobials, both in human health and in agriculture, produces an environment that selects for increasingly resistant bacteria.16”

• cites [16] Samreen, 2021, Environmental antimicrobial resistance and its drivers: a potential threat to public health, J Glob Antimicrob Resist sourceSupported

Adults are more likely to have comorbidities that lead to immunodeficiencies and increase the risk of opportunistic infections.

“Fourth, adults are more likely to have comorbidities45, 46 that lead to immunodeficiencies and increase the risk of opportunistic infections.47”

• cites [45] Schäfer, 2012, The influence of age, gender and socio-economic status on multimorbidity patterns in primary care. First results from the multicare cohort study, BMC Health Serv Res sourcePartly supported

  The Conclusions and Discussion report that, among patients aged 65 and older, increasing age was associated with a slightly greater number of chronic conditions. That supports an age-related comorbidity pattern, but the paper does not establish that adults generally are more likely to have comorbidities than children. The separate citation 47, not this source, is attached to the immunodeficiency and opportunistic-infection clause. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [46] Uijen, 2008, Multimorbidity in primary care: prevalence and trend over the last 20 years, Eur J Gen Pract sourceSupported
• cites [47] 2016Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

The decline in AMR mortality in children younger than 5 years coincides with widespread vaccination efforts and improved access to WASH.

“This decline coincides with widespread vaccination efforts and improved access to WASH37, 38”

• cites [37] Luh, 2016, Drinking water and sanitation: progress in 73 countries in relation to socioeconomic indicators, Bull World Health Organ sourcePartly supported

  The Discussion (page unavailable) reports that most studied countries increased their water and sanitation coverage between 2000 and 2012, supporting the improved-access-to-WASH portion of the sentence. The paper does not address vaccination efforts or establish that improved access coincided with a decline in AMR mortality among children younger than 5 years. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [38] Adamu, 2023, The impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria, Nat Commun sourcePartly supported

  The Discussion (page unavailable) reports that PCV10 coverage rose while vaccine-type pneumococcal carriage fell in two Nigerian settings, supporting the vaccination part of the sentence. It does not report a decline in antimicrobial-resistance mortality among children under 5 or address improved access to water, sanitation and hygiene (WASH). (LLM, conf=0.83)

  Experimental — accuracy not yet measured

The scarce data in some countries substantially affected the prevalence of resistance and relative risk modelling components.

“The scarce data in some countries substantially affected our prevalence of resistance and relative risk modelling components, akin to the situation in our previous publications.6, 50, 51, 60”

• cites [6] 2022, Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis, Lancet sourceSupported
• cites [50] 2022, The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis, Lancet Public Health sourceSupported
• cites [51] 2023, The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis, Lancet Reg Health AmNot checked yet

  Not checked in the free run.

• cites [60] 2024, The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis, Lancet Glob Health sourceSupported

The use of personal protective equipment, enhanced hand hygiene, and physical distancing, together with a greater number of focal points of infection prevention and control in LMICs, are salient factors that likely contributed to the temporary decrease in the transmission of resistant microorganisms while these measures were in effect.

“The use of personal protective equipment, enhanced hand hygiene, and physical distancing (together with a greater number of focal points of infection prevention and control in LMICs) are salient factors that likely contributed to the temporary decrease in the transmission of resistant microorganisms while these measures were in effect.65”

• cites [65] Tomczyk, 2021, Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: a global survey, J Antimicrob Chemother sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

The reduction in the number of microbiological cultures, elective procedures, and outpatient visits, alongside an increase in ICU admissions and admissions of chronically ill patients, could skew and subsequently bias AMR data used in the study.

“The reduction in the number of microbiological cultures, elective procedures, and outpatient visits, alongside an increase in ICU admissions and admissions of chronically ill patients, could skew and subsequently bias AMR data used in our study.65, 75”

• cites [65] Tomczyk, 2021, Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: a global survey, J Antimicrob Chemother sourcePartly supported

  The Discussion (AMR surveillance) says fewer cultures, elective surgeries and outpatient visits, together with more ICU admissions, could bias AMR data. But it reports a decrease—not an increase—in admissions of chronically ill patients, as the Results (Patient-case mix) also confirms. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [75] Clark, 2024, Changes to public health surveillance methods due to the COVID-19 pandemic: scoping review, JMIR Public Health Surveill sourcePartly supported

  The Results section, “Perspectives From Public Health Epidemiologists” (page unavailable), says COVID-19 made some previously reliable surveillance metrics difficult or impossible to interpret. The paper does not link that problem to AMR data or report the claimed changes in cultures, procedures, visits, or patient admissions; searches for “microbiological cultures” and “chronically ill” found no such discussion. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

The persistently high AMR mortality rate in sub-Saharan Africa reflects many of the challenges that LMICs broadly face, including fragmented health systems, inadequate ICU facilities, overcrowded ICUs, staff shortages, inadequate universal access to WASH, few trained infection prevention and control personnel, underdeveloped microbiological capacity, and limited access to antibiotics.

“The persistently high AMR mortality rate in this super-region reflects many of the challenges that LMICs broadly face, which include fragmented health systems, inadequate intensive care units (ICU) facilities, overcrowded ICUs, staff shortages, inadequate universal access to WASH, few trained infection prevention and control personnel, underdeveloped microbiological capacity, and limited access to”

• cites [61] Rudd, 2018, The global burden of sepsis: barriers and potential solutions, Crit Care sourcePartly supported

  The sections on critical care capacity, human resources, facilities, and diagnostic capacity describe overcrowded ICUs, staffing shortages, inadequate sanitation, and limited microbiology services in low-resource settings. The antimicrobials section also describes limited access to effective antibiotics in LMICs. But the paper does not establish a persistently high AMR mortality rate in sub-Saharan Africa or attribute that regional rate to these challenges; it also does not specifically document a shortage of trained infection prevention and control personnel. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

From 2022 to 2050, the number of deaths due to AMR is forecasted to increase by 69.6%.

“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.”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

Under the better care scenario, 92.0 million deaths could be cumulatively averted between 2025 and 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”

• AssumptionThe authors state this as an assumption: The better care scenario assumes future improvements in health-care quality and access to appropriate antimicrobials.

AMR mortality in people 5 years and older increased in all super-regions.

“AMR mortality in people 5 years and older increased in all super-regions.”

For deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally, from 57 200 attributable deaths in 1990 to 130 000 attributable deaths in 2021.

“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).”

AMR mortality decreased for children younger than 5 years in all super-regions.

“AMR mortality decreased for children younger than 5 years in all super-regions”

From 2022 to 2050, the number of DALYs is forecasted to increase by 9.4% to 46.5 million 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.”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class.

“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.”

An estimated 8.22 million deaths associated with AMR could occur globally in 2050.

“8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050.”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

Increases in deaths attributable to AMR will be largest among those 70 years and older, accounting for 65.9% of all-age deaths attributable to AMR in 2050.

“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).”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean.

“Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean.”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years.

“From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years”

In 2021, an estimated 4.71 million deaths were associated with bacterial AMR.

“In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR”

An estimated 1.91 million deaths attributable to AMR could occur globally in 2050.

“an estimated 1·91 million (1·56–2·26) deaths attributable to AMR”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

Trends in AMR mortality over the past 31 years varied substantially by age and location.

“Trends in AMR mortality over the past 31 years varied substantially by age and location.”

In 2021, an estimated 1.14 million deaths were attributable to bacterial AMR.

“including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR.”

From 1990 to 2021, deaths from AMR increased by over 80% for adults 70 years and older.

“yet increased by over 80% for adults 70 years and older.”

For deaths associated with AMR, meticillin-resistant Staphylococcus aureus increased the most globally, from 261 000 associated deaths in 1990 to 550 000 associated deaths in 2021.

“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).”

Under the Gram-negative drug scenario, 11.1 million AMR deaths could be averted.

“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.”

• AssumptionThe authors state this as an assumption: The Gram-negative drug scenario assumes future drug development that targets Gram-negative pathogens.

The relative risk of death for each pathogen-drug combination for a resistant infection compared with a drug-sensitive infection was estimated using data from 1238 sources representing 296 million samples from patients with outcome and resistance.

“Using data from 1238 sources representing 296 million samples from patients with outcome and resistance, we estimated the relative risk of death for each pathogen–drug combination for a resistant infection compared with a drug-sensitive infection using the meta-regression—Bayesian, regularised, trimmed tool (appendix 1 p 80).”

Global attributable DALY rate in 2050 is 496 per 100,000 (399-613).

“| Global | 281 000 (232 000–331 000) | 196 000 (170 000–221 000) | 178 000 (154 000–202 000) | 201 000 (165 000–245 000) | 5270 (4350–6200) | 2530 (2190–2860) | 2250 (1950–2550) | 2140 (1750–2630) | 60900 (47700–74100) | 46 800 (39 800–53 700) | 42 600 (36 100–49 000) | 46 500 (37 700–57 300) | 1140 (895–1390) | 604 (514–693) | 539 (458–621) | 496 (399–613) |”

The pathogen distribution models leveraged 24 million isolates and cases from 142 countries and territories to estimate the pathogen distribution of each infectious syndrome by age, year, and location.

“In total, the pathogen distribution models leveraged 24 million isolates and cases from 142 countries and territories to estimate the pathogen distribution of each infectious syndrome by age, year, and location, with each dataset including a unique spectrum of pathogens and groups of pathogens.”

Global associated DALYs in 2050 are 201,000 thousand (165,000-245,000).

“| Global | 281 000 (232 000–331 000) | 196 000 (170 000–221 000) | 178 000 (154 000–202 000) | 201 000 (165 000–245 000) | 5270 (4350–6200) | 2530 (2190–2860) | 2250 (1950–2550) | 2140 (1750–2630) | 60900 (47700–74100) | 46 800 (39 800–53 700) | 42 600 (36 100–49 000) | 46 500 (37 700–57 300) | 1140 (895–1390) | 604 (514–693) | 539 (458–621) | 496 (399–613) |”

Global all-age mortality rate attributable to AMR decreased from 1990 to 2021.

“The global all-age mortality rate attributable to AMR decreased from 19·8 deaths (15·8–23·9) per 100 000 in 1990 to 15·5 deaths (13·6–16·4) per 100 000 in 2019 and 14·5 deaths (12·7–16·2) per 100 000 in 2021.”

Excluding COVID-19, 8.47% (8.45-8.49) of infectious deaths in 2021 were attributable to AMR.

“Excluding COVID-19, 8·47% (8·45–8·49) of infectious deaths in 2021 were attributable to AMR.”

Global mortality from AMR increased minimally between 1990 and 2019.

“We show that global mortality from AMR increased minimally between 1990 and 2019, followed by a small decline that occurred during the COVID-19 pandemic.”

Global all-age mortality rate attributable to AMR was 14.5 deaths (12.7-16.2) per 100,000 in 2021.

“The global all-age mortality rate attributable to AMR decreased from 19·8 deaths (15·8–23·9) per 100 000 in 1990 to 15·5 deaths (13·6–16·4) per 100 000 in 2019 and 14·5 deaths (12·7–16·2) per 100 000 in 2021.”

Data on length of stay were available from 309 sources representing 38 million admissions.

“Data on length of stay were available from 309 sources representing 38 million admissions.”

Globally, children younger than 5 years had a 63.3% (95% UI 52.8-73.8) reduction in AMR-associated mortality from 1990 to 2021.

“Globally, children younger than 5 years had a more than 50% reduction in both attributable (60·4% [95% UI 47·6–73·1]) and associated (63·3% [52·8–73·8]) AMR mortality from 1990 to 2021.”

Global associated deaths in 2050 are 8.22 million (95% UI 6.85-9.65).

“| Global | 4780 (4000–5550) | 4940 (4430–5450) | 4710 (4230–5190) | 8220 (6850–9650) | 89·6 (75·0–104) | 63·8 (57·2–70·4) | 59·7 (53·6–65·7) | 87·7 (73·2–104) | 1060 (841–1270) | 1200 (1050–1350) | 1140 (1000–1280) | 1910 (1560–2260) | 19·8 (15·8–23·9) | 15·5 (13·6–17·4) | 14·5 (12·7–16·2) | 20·4 (16·6–24·2) |”

Adults 70 years and older experienced an 81.3% (95% UI 48.3-114.3) increase in AMR-associated mortality from 1990 to 2021.

“with adults 70 years and older experiencing a more than 80% increase in both attributable (89·5% [47·4–131·7]) and associated (81·3% [48·3–114·3]) mortality over this time period”

Global mortality from AMR had a small decline during the COVID-19 pandemic.

“We show that global mortality from AMR increased minimally between 1990 and 2019, followed by a small decline that occurred during the COVID-19 pandemic.”

Global DALYs attributable to AMR decreased from 60.9 million (95% UI 47.7-74.1) in 1990 to 42.6 million (36.1-49.0) in 2021.

“The global number of DALYs attributable to AMR decreased between 1990 (60·9 million [95% UI 47·7–74·1]) and 2021 (42·6 million [36·1–49·0]).”

The global all-age rate of DALYs attributable to AMR decreased from 1140 per 100 000 population (895-1390) in 1990 to 539 per 100 000 population (458-621) in 2021.

“the global all-age rate of DALYs attributable to AMR decreased from 1140 per 100 000 population (895–1390) in 1990 to 539 per 100 000 population (458–621) in 2021”

In people 5 years and older, deaths with sepsis more than doubled over the study period.

“In people 5 years and older, however, deaths with sepsis more than doubled over the study period”

The reference scenario indicates that deaths from AMR will increase by 2050 if remediation measures are not in place.

“Our reference scenario indicates that deaths from AMR will increase by 2050 if remediation measures are not in place.”

• AssumptionThe authors state this as an assumption: The reference scenario is a probabilistic forecast of the most likely future.

All age groups from 25 years and older had an increase in AMR mortality from 1990 to 2021.

“By contrast, all age groups from 25 years and older had an increase in AMR mortality over the same period”

In children younger than 5 years, deaths with sepsis decreased by more than 60% over the past 31 years.

“In children younger than 5 years, deaths with sepsis decreased by more than 60% over the past 31 years”

Information on the minimum inhibitory concentration of antibiotics was available in the remaining third of microbiology data sources.

“Information on the minimum inhibitory concentration of antibiotics was available in the remaining third of microbiology data sources.”

Of the 18.7 million sepsis deaths in people 5 years and older in 2021, 7.89 million (7.41-8.38) were due to COVID-19.

“of which 7·89 million (7·41–8·38) were due to COVID-19”

The percentage of deaths with sepsis associated with AMR was 22% in 2021.

“the percentage of deaths with sepsis that were associated with AMR increased from 29% in 1990 to 35% globally in 2019, before decreasing to 22% in 2021.”

The percentage of sepsis deaths attributable to AMR was 5.34% (4.95-5.70) in 2021.

“the percentage of sepsis deaths that were attributable to AMR increased from 6·41% (5·37–7·36) in 1990 to 8·51% (8·00–8·95) globally in 2019, before decreasing to 5·34% (4·95–5·70) in 2021.”

Global associated DALY rate in 2050 is 2140 per 100,000 (1750-2630).

“| Global | 281 000 (232 000–331 000) | 196 000 (170 000–221 000) | 178 000 (154 000–202 000) | 201 000 (165 000–245 000) | 5270 (4350–6200) | 2530 (2190–2860) | 2250 (1950–2550) | 2140 (1750–2630) | 60900 (47700–74100) | 46 800 (39 800–53 700) | 42 600 (36 100–49 000) | 46 500 (37 700–57 300) | 1140 (895–1390) | 604 (514–693) | 539 (458–621) | 496 (399–613) |”

Two-thirds of datasets used in the prevalence of resistance modelling reported a laboratory susceptibility interpretation rather than quantitative test values.

“Two-thirds of datasets used in the prevalence of resistance modelling reported a laboratory susceptibility interpretation rather than quantitative test values.”

Globally, children younger than 5 years had a 60.4% (95% UI 47.6-73.1) reduction in AMR-attributable mortality from 1990 to 2021.

“Globally, children younger than 5 years had a more than 50% reduction in both attributable (60·4% [95% UI 47·6–73·1]) and associated (63·3% [52·8–73·8]) AMR mortality from 1990 to 2021.”

For children younger than 5 years, from 1990 to 2021, deaths associated with and attributable to AMR decreased by 9% to 95% in all regions except Oceania.

“For children younger than 5 years, from 1990 to 2021, deaths associated with and attributable to AMR decreased by 9% to 95% in all regions except Oceania.”

The percentage of deaths with sepsis associated with AMR was 29% in 1990.

“the percentage of deaths with sepsis that were associated with AMR increased from 29% in 1990 to 35% globally in 2019, before decreasing to 22% in 2021.”

In 2019, there were 1.20 million (1.05-1.35) deaths attributable to AMR.

“In 2019, AMR mortality increased to 1·20 million (1·05–1·35) attributable deaths and 4·94 million (4·43–5·45) associated deaths.”

Global attributable deaths in 2050 are 1.91 million (1.56-2.26).

“| Global | 4780 (4000–5550) | 4940 (4430–5450) | 4710 (4230–5190) | 8220 (6850–9650) | 89·6 (75·0–104) | 63·8 (57·2–70·4) | 59·7 (53·6–65·7) | 87·7 (73·2–104) | 1060 (841–1270) | 1200 (1050–1350) | 1140 (1000–1280) | 1910 (1560–2260) | 19·8 (15·8–23·9) | 15·5 (13·6–17·4) | 14·5 (12·7–16·2) | 20·4 (16·6–24·2) |”

Among deaths attributable to or associated with AMR, trends diverged notably across age groups globally.

“Among deaths that were attributable to or associated with AMR, there was a notable divergence in trends across age groups (figure 2).”

The percentage of sepsis deaths attributable to AMR was 8.51% (8.00-8.95) globally in 2019.

“the percentage of sepsis deaths that were attributable to AMR increased from 6·41% (5·37–7·36) in 1990 to 8·51% (8·00–8·95) globally in 2019, before decreasing to 5·34% (4·95–5·70) in 2021.”

Global attributable death rate in 2050 is 20.4 per 100,000 (16.6-24.2).

“| Global | 4780 (4000–5550) | 4940 (4430–5450) | 4710 (4230–5190) | 8220 (6850–9650) | 89·6 (75·0–104) | 63·8 (57·2–70·4) | 59·7 (53·6–65·7) | 87·7 (73·2–104) | 1060 (841–1270) | 1200 (1050–1350) | 1140 (1000–1280) | 1910 (1560–2260) | 19·8 (15·8–23·9) | 15·5 (13·6–17·4) | 14·5 (12·7–16·2) | 20·4 (16·6–24·2) |”

In high-income Asia Pacific, 83.9% (81.7-86.1) of attributable AMR mortality was in adults 70 years and older in 2021.

“In comparison, in the high-income Asia Pacific region, 0·181% (0·1490–0·222) of the attributable AMR mortality occurred in children younger than 5 years and 83·9% (81·7–86·1) of the attributable AMR mortality was in adults 70 years and older for 2021”

Five regions had an increase of more than 10 000 deaths attributable to AMR: western sub-Saharan Africa, Tropical Latin America, high-income north America, southeast Asia, and south Asia.

“Five regions had an increase of more than 10 000 deaths attributable to AMR: western sub-Saharan Africa, Tropical Latin America, high-income north America, southeast Asia, and south Asia.”

Adults 70 years and older experienced an 89.5% (95% UI 47.4-131.7) increase in AMR-attributable mortality from 1990 to 2021.

“with adults 70 years and older experiencing a more than 80% increase in both attributable (89·5% [47·4–131·7]) and associated (81·3% [48·3–114·3]) mortality over this time period”

In 2021, there were 4.71 million (4.23-5.19) deaths associated with AMR.

“In 2021, 1·14 (1·00–1·28) million deaths attributable to AMR and 4·71 million (4·23–5·19) deaths associated with AMR occurred”

In western sub-Saharan Africa, 58.9% (54.8-63.0) of attributable AMR mortality occurred in children younger than 5 years in 2021.

“In western sub-Saharan Africa, 58·9% (54·8–63·0) of the attributable AMR mortality occurred in children younger than 5 years, and 15·8% (13·5–18·2) occurred in adults 70 years and older in 2021.”

Global attributable DALYs in 2050 are 46,500 thousand (37,700-57,300).

“| Global | 281 000 (232 000–331 000) | 196 000 (170 000–221 000) | 178 000 (154 000–202 000) | 201 000 (165 000–245 000) | 5270 (4350–6200) | 2530 (2190–2860) | 2250 (1950–2550) | 2140 (1750–2630) | 60900 (47700–74100) | 46 800 (39 800–53 700) | 42 600 (36 100–49 000) | 46 500 (37 700–57 300) | 1140 (895–1390) | 604 (514–693) | 539 (458–621) | 496 (399–613) |”

Global associated death rate in 2050 is 87.7 per 100,000 (73.2-104).

“| Global | 4780 (4000–5550) | 4940 (4430–5450) | 4710 (4230–5190) | 8220 (6850–9650) | 89·6 (75·0–104) | 63·8 (57·2–70·4) | 59·7 (53·6–65·7) | 87·7 (73·2–104) | 1060 (841–1270) | 1200 (1050–1350) | 1140 (1000–1280) | 1910 (1560–2260) | 19·8 (15·8–23·9) | 15·5 (13·6–17·4) | 14·5 (12·7–16·2) | 20·4 (16·6–24·2) |”

In 2021, there were 1.14 million (1.00-1.28) deaths attributable to AMR.

“In 2021, 1·14 (1·00–1·28) million deaths attributable to AMR and 4·71 million (4·23–5·19) deaths associated with AMR occurred”

The percentage of deaths with sepsis associated with AMR was 35% globally in 2019.

“the percentage of deaths with sepsis that were associated with AMR increased from 29% in 1990 to 35% globally in 2019, before decreasing to 22% in 2021.”

In people 5 years and older, AMR mortality increased from 1990 to 2021 in all regions except western Europe and central Europe.

“Conversely, in people 5 years and older, AMR mortality increased from 1990 to 2021 in all regions except for western Europe and central Europe.”

Among children younger than 5 years, the pathogens with the largest number of deaths attributable to AMR in 2021 were K pneumoniae, S pneumoniae, and E coli.

“Among children younger than 5 years, the pathogens with the largest number of deaths attributable to AMR in 2021 were K pneumoniae, S pneumoniae, and E coli (figure 3).”

In the better care scenario, a total of 92.0 million cumulative deaths (inclusive of deaths attributable to or associated with AMR as well as AMR unrelated deaths) would be averted between 2025 and 2050.

“In the better care scenario, we forecasted that a total of 92·0 million (95% UI 82·8–102) cumulative deaths (inclusive of deaths attrituable to or associated with AMR as well as AMR unrelated deaths) would be averted between 2025 and 2050 (appendix 1 pp 84, 116–117).”

Cumulatively from 2025 to 2050, the reference scenario forecasts 39.1 million deaths attributable to AMR.

“Cumulatively from 2025 to 2050, our reference scenario forecasts 39·1 million (33·0–46·0) deaths attributable to AMR and 169 million (145–196) deaths associated with AMR (appendix 1 pp 114–115).”

DALYs attributable to AMR are forecasted to increase from 42.6 million in 2022 to 46.5 million in 2050.

“DALYs attributable to AMR are forecasted to increase from 42·6 million (35·5–52·5) in 2022 to 46·5 million (37·7–57·3) in 2050.”

In the decomposition analysis, population growth alone would have increased AMR-associated deaths by 1 740 000 between 1990 and 2019, assuming other factors remained constant.

“Population growth | +1 740 000”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

In the decomposition analysis, changes in age structure alone would have increased AMR-associated deaths by 792 000 between 1990 and 2019, assuming other factors remained constant.

“Age structure | +792 000”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

In the decomposition analysis, the net change in AMR-associated deaths from 1990 to 2019 was an increase of 163 000.

“When combining all measured factors, there is a net increase of 163 000 AMR-associated deaths from 1990 to 2019.”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

In 2050, there will be 1.91 million annual deaths attributable to AMR globally.

“We estimated that in 2050, there will be 1·91 million (95% UI [1·56–2·26]) annual deaths attributable to AMR globally and 8·22 million (6·85–9·65) annual deaths associated with AMR (table 3; figure 6).”

In the decomposition analysis, changes in sepsis death rate alone would have decreased AMR-associated deaths by 3 090 000 between 1990 and 2019, assuming other factors remained constant.

“Sepsis death rate | −3 090 000”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

Among the super-regions, the decreases in AMR deaths in children younger than 5 years ranged from 36.4% in sub-Saharan Africa to 65.9% in south Asia.

“Among the super-regions, the decreases in children younger than 5 years ranged from 36·4% (16·4–51·9) in sub-Saharan Africa to 65·9% (55·1–74·9) in south Asia.”

Infection prevention and improvements in health-care quality and sepsis management prevented 3,090,000 AMR associated deaths from 1990 to 2019.

“Infection prevention and improvements in health-care quality and sepsis management prevented 3 090 000 AMR associated deaths from 1990 to 2019.”

Among people 5 years and older, the pathogens with the largest number of deaths attributable to AMR in 2021 were S aureus, A baumannii, and E coli.

“Among people 5 years and older, the pathogens with the largest number of deaths attributable to AMR in 2021 were S aureus, A baumannii, and E coli.”

Cumulatively from 2025 to 2050, the reference scenario forecasts 169 million deaths associated with AMR.

“Cumulatively from 2025 to 2050, our reference scenario forecasts 39·1 million (33·0–46·0) deaths attributable to AMR and 169 million (145–196) deaths associated with AMR (appendix 1 pp 114–115).”

In children younger than 5 years, the number of AMR attributable deaths decreased from 204,000 to 103,000 globally, a decrease of 49.6%.

“In children younger than 5 years, the number of AMR attributable deaths decreased from 204 000 (150–285) to 103 000 (65·0–156) globally, a decrease of 49·6% (34·1–61·3).”

Four pathogen-drug combinations had an increase of more than 25,000 attributable annual deaths from 1990 to 2021: MRSA, multidrug-resistant tuberculosis, carbapenem-resistant K pneumoniae, and carbapenem-resistant A baumannii.

“There were four pathogen–drug combinations with an increase of more than 25 000 attributable annual deaths from 1990 to 2021: MRSA, multidrug-resistant tuberculosis, carbapenem-resistant K pneumoniae, and carbapenem-resistant A baumannii (appendix 1 pp 135–157).”

The ageing and growing population contributed to an additional 2,530,000 AMR deaths from 1990 to 2019.

“This is overshadowed by the ageing and growing population, which contributed to an additional 2 530 000 AMR deaths, and changes in the pathogens and prevalence of resistance in pathogens causing sepsis, which led to 902 000 additional AMR deaths.”

The all-age rate of AMR attributable DALYs is forecasted to decrease from 536 per 100,000 population in 2022 to 496 per 100,000 in 2050.

“The all-age rate of AMR attributable DALYs is forecasted to decrease, however, from 536 per 100 000 population (450–658) in 2022 to 496 per 100 000 (399–613) in 2050.”

MRSA was the pathogen-drug combination with the largest increase in attributable burden globally, doubling from 57,200 attributable deaths in 1990 to 130,000 attributable deaths in 2021.

“The pathogen–drug combination with the largest increase in attributable burden globally was meticillin-resistant S aureus (MRSA), doubling from 57 200 attributable (34 100–80 300) deaths in 1990 to 130 000 attributable (113 000–146 000) deaths in 2021 (figure 5).”

All-age rates of DALYs attributable to AMR are forecasted to be highest in south Asia in 2050 at 687 DALYs per 100,000.

“All-age rates of DALYs attributable to AMR are forecasted to be highest in south Asia in 2050 (687 DALYs per 100 000 [527–881]; table 4).”

In the decomposition analysis, changes in the proportion of AMR bacteria deaths associated with resistance alone would have increased AMR-associated deaths by 675 000 between 1990 and 2019, assuming other factors remained constant.

“Proportion of AMR bacteria deaths associated with resistance | +675 000”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

In the Gram-negative scenario, 11.1 million cumulative AMR deaths would be averted between 2025 and 2050.

“In the Gram-negative scenario, we forecasted that 11·1 million (95% UI 9·08–13·2) cumulative AMR deaths would be averted between 2025 and 2050 (appendix 1 pp 84, 116–117).”

For deaths of people 70 years and older, an increase from 2022 to 2050 is forecasted in every super-region.

“For deaths of people 70 years and older, we forecasted an increase from 2022 to 2050 in every super-region.”

The greatest reduction in AMR deaths in children younger than 5 years globally was due to resistant S pneumoniae, with attributable deaths decreasing from 158 000 (95% UI 106 000-209 000) in 1990 to 35 100 (24 000-46 200) in 2021.

“The greatest reduction in AMR deaths in children younger than 5 years globally was due to resistant S pneumoniae, which decreased from 158 000 attributable (95% UI 106 000–209 000) deaths and 801 000 associated (604 000–997 000) deaths in 1990, to 35 100 attributable deaths (24 000–46 200) and 176 000 associated (133 000–220 000) deaths in 2021.”

In the decomposition analysis, changes in the proportion of sepsis deaths associated with AMR syndromes alone would have decreased AMR-associated deaths by 181 000 between 1990 and 2019, assuming other factors remained constant.

“Proportion of sepsis deaths associated with AMR syndromes | −181 000”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

Resistant S pneumoniae associated deaths in children younger than 5 years decreased from 801 000 (604 000-997 000) in 1990 to 176 000 (133 000-220 000) in 2021.

“The greatest reduction in AMR deaths in children younger than 5 years globally was due to resistant S pneumoniae, which decreased from 158 000 attributable (95% UI 106 000–209 000) deaths and 801 000 associated (604 000–997 000) deaths in 1990, to 35 100 attributable deaths (24 000–46 200) and 176 000 associated (133 000–220 000) deaths in 2021.”

The global AMR all-age mortality rate is forecasted to increase from 14.2 per 100,000 in 2022 to 20.4 per 100,000 in 2050.

“The global AMR all-age mortality rate is forecasted to increase from 14·2 per 100 000 (95% UI 12·3–16·7) in 2022 to 20·4 per 100 000 (16·6–24·2) in 2050, while the age-standardised mortality rate is forecasted to decrease from 14·2 per 100 000 (12·2–16·8) in 2022 to 12·4 per 100 000 (9·92–15·6) in 2050 (figure 6), indicating that the forecasted future trends of AMR burden will be largely driven by”

In children younger than 5 years, deaths attributable to AMR decreased for all pathogens except tuberculosis between 1990 and 2021.

“In children younger than 5 years, deaths attributable to AMR decreased for all pathogens except tuberculosis between 1990 to 2021.”

In the decomposition analysis, changes in the proportion of AMR syndrome deaths associated with AMR bacteria alone would have increased AMR-associated deaths by 227 000 between 1990 and 2019, assuming other factors remained constant.

“Proportion of AMR syndrome deaths associated with AMR bacteria | +227 000”

• AssumptionThe authors state this as an assumption: In the decomposition analysis, each factor's estimated effect assumes that all other factors remained constant.

In 2050, there will be 8.22 million annual deaths associated with AMR globally.

“We estimated that in 2050, there will be 1·91 million (95% UI [1·56–2·26]) annual deaths attributable to AMR globally and 8·22 million (6·85–9·65) annual deaths associated with AMR (table 3; figure 6).”

By 2030, the global number of deaths attributable to AMR is forecasted to be 1.28 million.

“By 2030, the global number of deaths attributable to AMR is forecasted to be 1·28 million (95% UI 1·10–1·48).”

In sub-Saharan Africa, the number of deaths averted in children younger than 5 years was similar to that in people 70 years and older, with 6.98 million versus 7.02 million deaths averted.

“Compared with the other GBD super-regions, sub-Saharan Africa was exceptional with a similar number of deaths averted in children younger than 5 years compared with those 70 years and older, with 6·98 million (5·25–8·98) deaths averted in children younger than 5 years versus 7·02 million (6·31–7·61) in the oldest age group (figure 8).”

In people 5 years and older, attributable AMR deaths increased in all but three pathogens: Salmonella Paratyphi, Salmonella Typhi, and Serratia, between 1990 and 2021.

“Conversely, attributable AMR deaths in people 5 years and older increased in all but three pathogens: Salmonella Paratyphi, Salmonella Typhi, and Serratia.”

Changes in the pathogens and prevalence of resistance in pathogens causing sepsis led to 902,000 additional AMR deaths from 1990 to 2019.

“This is overshadowed by the ageing and growing population, which contributed to an additional 2 530 000 AMR deaths, and changes in the pathogens and prevalence of resistance in pathogens causing sepsis, which led to 902 000 additional AMR deaths.”

Drug-resistant S pneumoniae attributable deaths in people 5 years and older increased from 100 000 (70 700-129 000) in 1990 to 120 000 (96 200-144 000) in 2021.

“In contrast, drug-resistant S pneumoniae increased in people 5 years and older, rising from 100 000 (70 700–129 000) attributable and 496 000 (393 000–599 000) associated deaths in 1990, to 120 000 (96 200–144 000) attributable and 606 000 (533 000–679 000) associated deaths in 2021.”

Despite prevention options and its designation as highly treatable, MRSA remains the pathogen-drug combination responsible for the greatest health loss globally in 2021.

“Despite these prevention options, and its designation as highly treatable with several alternative antibiotics available, MRSA remains the pathogen–drug combination responsible for the greatest health loss globally in 2021.”

In people older than 70 years, AMR mortality increased by more than 80%.

“In this age group, we found that AMR mortality increased by more than 80%.”

S pneumoniae had the most substantial decline in AMR burden, with associated deaths decreasing from 1.30 million (95% UI 1.01-1.58) in 1990 to 782 000 (681 000-884 000) in 2021.

“The pathogen with the most substantial decline was S pneumoniae, with a decrease from 1·30 million (95% UI 1·01–1·58) associated deaths and 258 000 (179 000–336 000) attributable deaths in 1990, to 782 000 (681 000–884 000) associated and 155 000 (122 000–188 000) attributable deaths in 2021.”

From 2022 to 2050, the increases in the global number of AMR attributable deaths amount to a 69.6% increase by 2050.

“From 2022 to 2030, the increases in the global number of AMR attributable deaths amount to a 13·4 % (7·8–18·8) increase by 2030, and a 69·6% (51·5–89·2) increase by 2050.”

The greatest benefits of the better care scenario would be in the south Asia, sub-Saharan Africa, and southeast Asia, east Asia, and Oceania super-regions with 31.7 million, 25.2 million, and 18.7 million deaths averted, respectively.

“The greatest benefits would be in the south Asia, sub-Saharan Africa, and southeast Asia, east Asia, and Oceania super-regions with 31·7 million (26·8–37·2), 25·2 million (21·2–29·8), and 18·7 million (14·4–22·8), respectively.”

Staphylococcus aureus had the greatest increase in attributable AMR deaths, rising from 103 000 (73 900-133 000) in 1990 to 196 000 (177 000-215 000) in 2021.

“The pathogen with the greatest increase was Staphylococcus aureus, rising from 103 000 (73 900–133 000) attributable deaths in 1990 to 196 000 (177 000–215 000) attributable deaths in 2021.”

The age-standardised AMR mortality rate is forecasted to decrease from 14.2 per 100,000 in 2022 to 12.4 per 100,000 in 2050.

“The global AMR all-age mortality rate is forecasted to increase from 14·2 per 100 000 (95% UI 12·3–16·7) in 2022 to 20·4 per 100 000 (16·6–24·2) in 2050, while the age-standardised mortality rate is forecasted to decrease from 14·2 per 100 000 (12·2–16·8) in 2022 to 12·4 per 100 000 (9·92–15·6) in 2050 (figure 6), indicating that the forecasted future trends of AMR burden will be largely driven by”

Deaths averted in children younger than 5 years in the Gram-negative scenario will be largest in sub-Saharan Africa and south Asia, where 637,000 and 309,000 cumulative AMR deaths were forecasted to be averted, respectively.

“Deaths averted in children younger than 5 years will be largest in sub-Saharan Africa and south Asia, where 637 000 (409–950) and 309 000 (218–454) cumulative AMR deaths were forecasted to be averted, respectively.”

From 2022 to 2030, the increases in the global number of AMR attributable deaths amount to a 13.4% increase by 2030.

“From 2022 to 2030, the increases in the global number of AMR attributable deaths amount to a 13·4 % (7·8–18·8) increase by 2030, and a 69·6% (51·5–89·2) increase by 2050.”

All but one of the pathogen-drug combinations rated by the WHO Bacterial Priority Pathogens List to have low or medium-low treatability had an increasing burden from 1990 to 2021.

“All but one of the pathogen–drug combinations rated by the WHO Bacterial Priority Pathogens List to have low or medium-low treatability had an increasing burden from 1990 to 2021;”

Even under the Gram-negative drug scenario's optimistic assumptions, a total of 28.03 million annual AMR deaths still occur by 2050.

“however, a total of 28·03 million (23·7–32·8) annual AMR deaths still occur by 2050, even under this scenario's optimistic assumptions.”

The reference scenario mortality estimates suggest a continued increase in AMR mortality, leading to 1·91 million attributable deaths and 8·22 million associated AMR deaths in 2050.

“Our reference scenario mortality estimates suggest a continued increase in AMR mortality, leading to 1·91 million attributable deaths and 8·22 million associated AMR deaths in 2050.”

When someone dies from sepsis, the probability that the organism causing infection is drug-resistant is 25% higher in 2019 relative to 1990.

“When looking at the role of AMR in sepsis deaths, we describe a growing and concerning trend that when someone dies from sepsis, the probability that the organism causing infection is drug-resistant is 25% higher in 2019 relative to 1990.”

Only fluoroquinolone-resistant Salmonella Typhi had a decreasing burden among those pathogen-drug combinations.

“only fluoroquinolone-resistant Salmonella Typhi had a decreasing burden, largely due to decreases in global Salmonella Typhi incidence.”

The number of deaths averted between 2025 and 2050 under the better care scenario is five-times greater than those saved by the Gram-negative drug scenario.

“The number of deaths averted between 2025 and 2050 under the better care scenario is five-times greater than those saved by the Gram-negative drug scenario.”

There is rising resistance to critically important antimicrobials.

“Perhaps more importantly, we found rising resistance to critically important antimicrobials.”

There was a decline in AMR burden during the COVID-19 pandemic within the years captured by the study (2020 and 2021).

“We found a decline in AMR burden during the COVID-19 pandemic within the years captured by our study (2020 and 2021).”

The opposing trends in the burden of AMR deaths between younger and older individuals explain the moderate future increase in global number of DALYs versus number of deaths.

“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.”

In total, 520 million individual records or isolates covering 19 513 study-location-years were used as input data to the AMR estimation process.

“In total, there were 520 million individual records or isolates covering 19 513 study-location-years used as input data to the AMR estimation process.”

The 2019 global AMR estimate provides only a cross-section of burden, limiting the ability to understand the historical trend of AMR and evaluate policies implemented to reduce its impact.

“While this estimate has been used to inform research and policy priorities, such as the 2024 WHO Bacterial Priority Pathogens List,8 it provides only a cross-section of burden, limiting the ability to understand the historical trend of AMR and evaluate policies implemented to reduce its impact.”

• cites [8] 2024Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Relationships between proportions of resistance when classifying data using other versions of CLSI and EUCAST guidelines were inferred and used to create adjustment factors to correct data that only reported laboratory interpretations.

“These relationships were then used to create adjustment factors and correct the data that only reported laboratory interpretations as described in appendix 1 (pp 51–55).”

Data providers used several guidelines (and therefore breakpoints) to interpret test results, which potentially introduced bias.

“Data providers used several guidelines (and therefore breakpoints) to interpret test results, which potentially introduced bias.”

Due to data sparsity associated with drug-resistant N gonorrhoeae, only a non-fatal estimate was produced for this pathogen.

“Due to data sparsity associated with drug-resistant N gonorrhoeae, we only produced a non-fatal estimate for this pathogen.”

Tertiary rates of resistance were adjusted by crosswalking them to data from non-tertiary and mixed facilities to account for bias in resistance data provided by tertiary care facilities.

“Additionally, to account for bias in resistance data provided by tertiary care facilities, we adjusted tertiary rates of resistance by crosswalking them to data from non-tertiary and mixed facilities (appendix 1 pp 51–55).”

In case of inconsistent observations, the method still provides the multinomial distribution that approximately matches the margins, best in the least squares sense.

“In case of inconsistent observations, the method still provides the multinomial distribution that approximately matches the margins, best in the least squares sense.”

In the decade since the Review on Antimicrobial Resistance publication, global AMR estimates have been sparse.

“In the decade since its publication, however, global AMR estimates have been sparse.”

The forecasts of alternative scenarios show the potential to avert large numbers of deaths over the next quarter century.

“Our forecasts of alternative scenarios show the potential to avert large numbers of deaths over the next quarter century.”

Due to data sparsity, the relative risk of death was estimated by antibiotic class, pathogen, and infectious syndrome.

“Because of data sparsity, we estimated the relative risk by antibiotic class, pathogen, and infectious syndrome”

So far, time trends in AMR have been limited to select high-income locations for a small number of pathogen-drug combinations.

“So far, time trends in AMR have been limited to select high-income locations for a small number of pathogen–drug combinations.”

Infection prevention might be a highly effective intervention in reducing AMR burden.

“serves as an important reminder to the global health community and policy makers that infection prevention might be a highly effective intervention in reducing AMR burden.39”

• cites [39] Lewnard, 2024, Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis, Lancet sourceNot checked — no full text of the source

Without additional measures, the 10% reduction in AMR mortality proposed in the 10-20-30 by 2030 target will not be reached.

“This suggests that without additional measures, we will not reach the 10% reduction in AMR mortality proposed in the 10-20-30 by 2030 target.3”

• cites [3] 2024, Antimicrobial resistance: an agenda for all, LancetNot checked yet

  Not checked in the free run.

The rising AMR and sepsis mortality in older adults has been masked by traditional global health metrics.

“First, the rising AMR and sepsis mortality in older adults has been masked by traditional global health metrics.”

The complex interplay between an older population, improvements in the health-care system, and the emergence of more resistant and deadly pathogens resulted in a net increase of 163,000 deaths associated with AMR from 1990 to 2019.

“Ultimately, the complex interplay between an older population, improvements in the health-care system, and the emergence of more resistant and deadly pathogens resulted in a net increase of 163 000 deaths associated with AMR from 1990 to 2019.”

Preventing infections through existing measures can have an outsized effect on AMR burden through multiple pathways.

“These findings reinforce some of the major themes presented in the recent Lancet series on AMR,40 that preventing infections through existing measures can have an outsized effect on burden through multiple pathways.39”

• cites [40]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [39] Lewnard, 2024, Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis, Lancet sourceNot checked — no full text of the source

Much of the reduction in AMR mortality in children younger than 5 years is due to a decrease in drug-resistant S pneumoniae and in pathogens commonly spread through faecal-oral transmission.

“Much of this reduction is due to a decrease in drug-resistant S pneumoniae and in pathogens commonly spread through faecal–oral transmission (eg, Salmonella, Shigella, and enteropathogenic or enterotoxigenic E coli).”

The forecasted future trends of AMR burden will be largely driven by changes in population size and age structure.

“indicating that the forecasted future trends of AMR burden will be largely driven by changes in population size and age structure.”

The growth of the older adult population could have a compounding effect on AMR by increasing vulnerability to infection while increasing the volume of antimicrobials used, creating greater selection pressure for resistance to emerge.

“This could have a compounding effect on AMR—increasing the vulnerability to infection while increasing the volume of antimicrobials used—creating greater selection pressure for resistance to emerge.”

In contrast to MRSA, there are fewer evidence-based prevention measures for carbapenem-resistant Acinetobacter and Enterobacterales, particularly at the population level.

“In contrast to MRSA, there are fewer evidence-based prevention measures for carbapenem-resistant Acinetobacter and Enterobacterales, particularly at the population level.”

Interventions that are effective in younger age groups, such as vaccines, might be less effective in older adults.

“Second, interventions that are effective in younger age groups, such as vaccines, might be less effective in older adults.”

Much of the reduction in all-age mortality rate is due to infection prevention, improvements in the management of sepsis, and reductions in sepsis mortality in children younger than 5 years.

“Much of this reduction is due to infection prevention, improvements in the management of sepsis, and reductions in sepsis mortality in children younger than 5 years.”

A possible effect of applying the β-lactam hierarchy to S pneumoniae is an overestimation of the burden of carbapenem resistance in S pneumoniae relative to other β-lactams, specifically penicillin and third-generation cephalosporins.

“a possible effect of applying this hierarchy to S pneumoniae is an overestimation of the burden of carbapenem resistance in S pneumoniae relative to other β-lactams, specifically penicillin and third-generation cephalosporins.”

• AssumptionThe authors state this as an assumption: An isolate resistant to both third-generation cephalosporins and carbapenems has its attributable burden assigned to carbapenems (β-lactam hierarchy).

The forecast and scenarios of AMR burden to 2050 are subject to the limitations in the historical estimates, including data availability and quality, because forecast trends are built from historical estimates.

“Our forecast and scenarios of AMR burden to 2050 are also subject to the limitations in the historical estimates, including data availability and quality, as our forecast trends are built of historical estimates.”

Due to difficulty calculating the 85th percentile case-fatality rate, typhoid, paratyphoid, and invasive non-typhoidal Salmonella were excluded from the better care scenario.

“Due to difficulty calculating the 85th percentile case-fatality rate, typhoid, paratyphoid, and invasive non-typhoidal Salmonella was excluded.”

The forecasts for the better care scenario do not incorporate the effects of infectious diseases outside of those that contributed to the AMR mortality envelope.

“Our forecasts for the better care scenario do not incorporate the effects infectious diseases outside of those that contributed to the AMR mortality envelope (appendix 1 p 20).”

Seven of 204 countries and territories had no data available for any of the modelling components.

“In our study, seven of 204 countries and territories had no data available for any of our modelling components.”

Estimates of resistance before 2000 rely heavily on modelled temporal trends and covariates.

“Correspondingly, our estimates of resistance before 2000 rely heavily on modelled temporal trends and covariates.”

In some countries, available data are fragmented, undersampled, or not representative of the broader population.

“In some countries, available data are fragmented, undersampled, or not representative of the broader population.”

The decreasing burden of fluoroquinolone-resistant Salmonella Typhi was largely due to decreases in global Salmonella Typhi incidence.

“only fluoroquinolone-resistant Salmonella Typhi had a decreasing burden, largely due to decreases in global Salmonella Typhi incidence.”

The borrowing of strength for the effect of resistance on mortality from other pathogens with resistance to the same antimicrobial class is likely a stronger assumption for S pneumoniae than for Enterobacterales, given the prevalence of input data from carbapenemase-producing carbapenem-resistant Enterobacterales and S pneumoniae's distinct mechanism of resistance.

“which is likely a stronger assumption for S pneumoniae than the Enterobacterales given the prevalence of input data from Carbapenemase producing carbapenem-resistant enterobacterales and S pneumoniae's distinct mechanism of resistance.”

The most significant limitation of the study is the scarcity of data from some LMICs on the distribution of pathogens by infectious syndrome, the relative risk of resistance for key pathogen-drug combinations, and the number of deaths related to infections.

“This study has several limitations (many of which have been discussed previously), with the most significant being the scarcity of data from some LMICs on the distribution of pathogens by infectious syndrome, the relative risk of resistance for key pathogen–drug combinations, and the number of deaths related to infections.”

Overall improvements to health-care systems, including access to existing antibiotics, could be far more impactful than drug development alone.

“This shows that overall improvements to health-care systems, including access to existing antibiotics, could be far more impactful than drug development alone.”

The reference forecasts suggest that without additional measures we will fail to hit the 10% reduction in AMR mortality proposed in the 10-20-30 by 2030 target.

“Our reference forecasts suggest that without additional measures we will fail to hit the 10% reduction in AMR mortality proposed in the 10-20-30 by 2030 target.”

The uneven temporal distribution of available data from various regions and countries complicates the accurate representation of global, regional, and national AMR dynamics, potentially affecting the reliability and interpretation of time trend analyses.

“One constraint is the uneven temporal distribution of available data from various regions and countries, which complicates the accurate representation of global, regional, and national AMR dynamics—potentially affecting the reliability and interpretation of our time trend analyses.”

To our knowledge, this study is the first to report changes in AMR burden over time by using attributable and associated counterfactual scenarios while covering a wide array of pathogens and pathogen-drug combinations, with global and regional estimates for 204 countries and territories.

“Therefore, to our knowledge, this study is the first to report changes in AMR burden over time by using attributable and associated counterfactual scenarios while covering a wide array of pathogens and pathogen–drug combinations, with global and regional estimates for 204 countries and territories.”

There is a substantial scarcity of data linking laboratory results to outcomes such as mortality.

“We also acknowledge a substantial scarcity of data linking laboratory results to outcomes such as mortality, an issue also reflected in our previous research.”