Abstract
Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen-drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date.
Generated Summary
This systematic analysis, led by the Antimicrobial Resistance Collaborators, investigates the global burden of bacterial antimicrobial resistance (AMR) in 2019. The study employed a comprehensive approach, analyzing data from 204 countries and territories, focusing on 23 pathogens and 88 pathogen-drug combinations. The research combined data from various sources, including literature reviews, hospital systems, and surveillance data, to estimate deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR. The methodology involved predictive statistical modeling to generate estimates for all locations, even those lacking data, and incorporated five broad components: deaths, proportion of infectious deaths, proportion of infectious syndrome deaths, pathogen resistance to antibiotics, and the excess risk of death related to resistance. The study’s objective was to provide the most comprehensive estimates of the global AMR burden to date, offering crucial insights for policy decisions and intervention strategies.
Key Findings & Statistics
- The study estimated 4.95 million (3.62–6.57) deaths associated with bacterial AMR in 2019, including 1.27 million (0.911–1.71) deaths attributable to bacterial AMR.
- The all-age death rate attributable to resistance was highest in western sub-Saharan Africa, at 27.3 deaths per 100,000 (20.9–35.3), and lowest in Australasia, at 6.5 deaths (4.3–9.4) per 100,000.
- Lower respiratory infections accounted for over 1.5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome.
- The six leading pathogens for deaths associated with resistance (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929,000 (660,000–1,270,000) deaths attributable to AMR and 3.57 million (2.62–4.78) deaths associated with AMR in 2019.
- Meticillin-resistant S aureus caused more than 100,000 deaths attributable to AMR in 2019, while six more each caused 50,000–100,000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.
- The study estimated that in 2019, 1.27 million deaths (95% UI 0.911–1.71) were directly attributable to resistance (ie, based on the counterfactual scenario that drug-resistant infections were instead drug susceptible) in the 88 pathogen-drug combinations evaluated.
- On the basis of a counterfactual scenario of no infection, it was estimated that 4.95 million deaths (3.62–6.57) were associated with bacterial AMR globally in 2019.
- Australasia had the lowest AMR burden in 2019, with 6.5 deaths per 100,000 (95% UI 4.3–9.4) attributable to AMR and 28.0 deaths per 100,000 (18.8–39.9) associated with AMR.
- Western sub-Saharan Africa had the highest burden, with 27.3 deaths per 100,000 (20.9–35.3) attributable to AMR and 114.8 deaths per 100,000 (90.4–145.3) associated with AMR.
- Three infectious syndromes dominated the global burdens attributable to and associated with AMR in 2019: lower respiratory and thorax infections, bloodstream infections, and intra-abdominal infections.
- Combined, these three syndromes accounted for 78.8% (95% UI 70.8–85.2) of deaths attributable to AMR in 2019; lower respiratory infections alone accounted for more than 400,000 attributable deaths and 1.5 million associated deaths.
- In 2019, six pathogens were each responsible for more than 250,000 deaths associated with AMR (E coli, Staphylococcus aureus, K pneumoniae, S pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa).
- Meticillin-resistant S aureus was the one pathogen-drug combination in the analysis with more than 100,000 deaths and 3.5 million DALYs attributable to resistance.
- Six more pathogen-drug combinations each caused between 50,000 and 100,000 resistance-attributable deaths in 2019: MDR excluding XDR tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae.
Other Important Findings
- The study’s estimates indicate that bacterial AMR is a health problem of a magnitude comparable to major diseases such as HIV and malaria, and potentially much larger.
- AMR is a problem in all regions, with the highest rates of AMR burden in sub-Saharan Africa in 2019.
- The study found that high-quality data on infectious disease, pathogens, and AMR are only sparsely available in many low-income settings, emphasizing the need for expanded microbiology laboratory capacity and data collection systems.
- Resistance to fluoroquinolones and β-lactam antibiotics (carbapenems, cephalosporins, and penicillins) accounted for over 70% of deaths attributable to AMR across pathogens.
- The study highlights the need for specific policies to target the deadliest pathogen-drug combinations, particularly through expanded infection prevention and control programs, improving access to essential second-line antibiotics where needed, and promoting vaccine and antibiotic development.
Limitations Noted in the Document
- The study acknowledges limitations, including data sparsity from many low- and middle-income countries (LMICs) on pathogen distribution, resistance prevalence, and deaths involving infection.
- The study faced challenges in data standardization, particularly in classifying resistance and accounting for selection bias in surveillance data.
- The study used a two-stage spatiotemporal modeling framework, and the relative risk was assumed to be the same for every syndrome, location, and age group due to data sparsity.
- The study’s reliance on the GBD 2019 framework, while providing a robust basis, is also a limitation, as it depends on the quality of the underlying data and the assumptions made in the GBD study.
- The study notes that the burden of carbapenem-resistant A baumannii in high-income settings is higher than that of third-generation cephalosporin-resistant E coli.
Conclusion
The study provides the most comprehensive assessment of the global burden of AMR, identifying it as a leading cause of death worldwide, with the highest burdens in low-resource settings. The findings highlight the need for location-specific policy decisions, especially concerning infection prevention and control programs, access to essential antibiotics, and research and development of new vaccines and antibiotics. The analysis underscores the importance of addressing the scarcity of data in many low-income settings, emphasizing the expansion of microbiology laboratory capacity and data collection systems. The study’s estimates reveal that bacterial AMR is a major global health threat comparable to major diseases, and potentially much larger. The highest burden is in sub-Saharan Africa. The dominance of lower respiratory infections, bloodstream infections, and intra-abdominal infections in the burden of AMR underlines the need for targeted interventions. The study’s findings also indicate the need for more attention, funding, capacity building, and pathogen-specific priority setting from the broader global health community. The study emphasizes that resistance to fluoroquinolones and β-lactam antibiotics accounted for a significant portion of AMR-related deaths. The authors underscore the importance of maintaining investment in the development pipeline for new antibiotics and access to second-line antibiotics in locations without widespread access to such medications. The study’s conclusions emphasize the urgent need for comprehensive global and nationally tailored responses to combat AMR, with particular attention to the high burden in low-resource settings.