In what may be the first estimate of bacterial deaths worldwide, researchers reported 33 bacterial pathogens were responsible for more than 1 in 7 deaths in 2019, with five pathogens linked to slightly more than half of those deaths.
"Deaths associated with these bacteria would rank as the second leading cause of death globally in 2019," behind ischemic heart disease, write senior investigator Mohsen Naghavi, MD, PhD, from the University of Washington, Seattle, and a host of GBD 2019 Antimicrobial Resistance Collaborators.. "Hence, they should be considered an urgent priority for intervention within the global health community."
The findings, published online today in The Lancet, point to Staphylococcus aureus as the leading cause of bacterial death in 135 countries and Streptococcus pneumoniae associated with the most deaths in children younger than 5 years. The three other most clinically significant pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
The study estimated S aureus was linked to more than 1 million deaths globally in 2019, whereas the other four pathogens were associated with more than 500,000 each.
"This study can be used to guide strategies for reducing the burden of bacterial infectious diseases, including infection prevention and control measures, vaccine development and implementation, and the availability of basic acute care services," the authors write.
33 Pathogens, 204 Countries, and 11 Infectious Syndromes
The study estimated the fatal burden associated with infection caused by 33 bacterial species or genera across 204 countries or territories and across 11 infectious syndromes. The researchers included bacteria both resistant and susceptible to antimicrobials, but they excluded Mycobacterium tuberculosis, because it already is a major focus of a global public health initiative, they wrote.
Researchers used data derived from death certificates, hospital discharge records, mortality surveillance, literature reviews, and microbial data, as well as estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study.
In three modeling steps, they estimated:
the overall number of deaths in which infection had a role
the infectious syndromes responsible for these deaths
the pathogens associated with these infectious syndromes
"An infectious syndrome is the infection directly responsible for sepsis and serves as the bridge between the underlying cause of death and sepsis," the authors explain.
The three syndromes responsible for the most deaths were lower respiratory infections, bloodstream infections, and peritoneal and intra-abdominal infections. The syndromes responsible for the most deaths varied across locations.
Overall, lower respiratory infections were responsible for 4 million deaths, bloodstream infections accounted for 2.91 million deaths, and peritoneal and intra-abdominal infections for 1.28 million deaths.
"There was substantial variation in which pathogen was the most dominant across different infectious syndromes," the authors note, with S pneumoniae being the leading cause of fatal lower respiratory infections (653,000 deaths), S aureus being the leading cause of fatal bloodstream infections (299,000 deaths), and and E coli being the leading cause of fatal peritoneal and intra-abdominal infections (290,000 deaths).
There was "considerable variation" by region in the burden of bacterial infections, with the greatest number of deaths occurring in sub-Saharan Africa, "where we clearly saw the effect of both Gram-positive and Gram-negative pathogens," they write. The disparate burden in sub-Saharan Africa is magnified by the substantial years of life lost (YLL) burden in this region as well, they add.
Overall, the age-standardized mortality rate associated with these bacterial pathogens was highest in sub-Saharan Africa (230 deaths per 100,000 population) and lowest in the high-income super-region (52.2 deaths per 100,000 population).
"By estimating mortality and YLLs for a broad range of pathogens and infectious syndromes, we have produced a global account of bacteria for which the burden was previously unknown and, perhaps, underappreciated," they note.
Little Public Health Attention
Of the five most clinically significant pathogens they identified, only S pneumoniae has been the focus of global surveillance and public health initiatives, they wrote, with the others "not a major focus of any global public health initiatives."
The investigators emphasized four interventions to address the burden of these bacterial pathogens:
adequate acute care services, including "timely access to appropriate antibiotics, microbiological capacity to identify the responsible pathogen of an infection, and provision of supportive care"
a "strategic approach and ample investment in the development of new and effective antibiotics"
Although this study examined both antimicrobial susceptible and resistant bacterial pathogens, antimicrobial resistance (AMR) is "the weakest link" that threatens "the whole of modern medicine and public health," according to a perspective published a week earlier in PLoS Biology by Christiane Dolecek, MD, PhD, from the University of Oxford, Oxford, United Kingdom, and Mahidol University, Bangkok, Thailand, and colleagues.
Both Dolecek and Naghavi, along with the Antimicrobial Resistance Collaborators, contributed to "the GRAM report," a systematic analysis of the global burden of bacterial antimicrobial resistance in 2019 published earlier this year in The Lancet. They estimated AMR was a contributing factor in 4.3 million deaths and directly contributed to 1.27 million deaths that year.
"The main principles to combat bacterial drug-resistant infections have been clearly defined and agreed upon…However, their implementation has proven much harder," wrote editorialist Dolecek and colleagues.
"A lot remains to be done — even in wealthier countries, particularly in incentivising antibiotic stewardship, research and innovation (R&I), and supporting pull mechanisms to delink antibiotic development from sales volume. However, the reality in many low- and middle-income countries is that dedicated resources for the actions necessary to deliver these plans are lacking, jeopardizing their implementation."
Emphasizing that "we are on a dire trend," they concluded, "we must urgently refocus on AMR; otherwise, more precious lives will be lost."
The Global Burden of Disease study was funded by Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund. The GRAM project is funded by the Fleming Fund of the UK Department of Health and Social Care, the Wellcome Trust, and the Bill and Melinda Gates Foundation. The study authors and editorialists report no relevant financial relationships.
Lancet. Published online November 21, 2022. Full text
Kate Johnson is a Montreal-based freelance medical journalist who has been writing for more than 30 years about all areas of medicine.
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