Global Mortality Burden of Antimicrobial-Resistant Bloodstream Infections: An Analysis of Global Burden of Disease Study 2021 Estimates

Background: Bloodstream infections (BSIs) are a leading cause of global mortality, and antimicrobial resistance (AMR) threatens the effectiveness of their treatment. A comprehensive, long-term assessment of AMR burden in BSIs is critical to guide antimicrobial stewardship, optimize antibiotic access, and inform resource allocation. Methods: We performed a secondary analysis of Global Burden of Disease (GBD) 2021 estimates to quantify AMR-associated and AMR-attributable mortality, including absolute death counts and age-standardized mortality rates (ASMRs), for bacterial BSIs from 1990 to 2021. These estimates refer to deaths allocated to the BSI category within the GBD framework and do not necessarily represent microbiologically confirmed BSIs. Results: In 2021, the GBD BSI category included an estimated 1.82 million (95% UI: 1.65, 1.98) AMR-associated deaths and 0.46 million (0.41, 0.51) AMR-attributable deaths. From 1990 to 2021, the absolute numbers of both AMR-associated and AMR-attributable deaths increased, whereas global ASMRs declined. ASMRs varied substantially across regions, with the highest rates in Sub-Saharan Africa, and were higher in males than females. Age-specific mortality rates declined across all age groups, with neonatal rates remaining the highest, although absolute death counts decreased among neonates and increased among older adults (≥60 years). Based on modeled point estimates, at the pathogen–drug level, macrolide-resistant and methicillin-resistant Staphylococcus aureus were among the leading contributors to AMR-associated deaths, whereas methicillin-resistant S. aureus and carbapenem-resistant Acinetobacter baumannii were among the leading contributors to AMR-attributable deaths. At the drug-class level, resistance to fluoroquinolones, third-generation cephalosporins, and trimethoprim-sulfamethoxazole contributed substantially to the associated burden, whereas carbapenem resistance accounted for the largest number of AMR-attributable deaths. Conclusions: From 1990 to 2021, global ASMRs declined despite increases in the absolute numbers of AMR-related deaths from BSIs, underscoring the importance of considering both measures in public health planning. Substantial geographical inequalities and the mortality associated with key pathogen–drug combinations highlight the need for context-specific strategies to strengthen antimicrobial stewardship, improve infection prevention, and ensure equitable access to effective treatment.