In a truly harrowing development, the highly-anticipated GRAM report has shockingly revealed that 1.2 million deaths were directly caused by antimicrobial resistance (AMR) in 2019, with antimicrobial-resistant infections playing a significant role in an additional 4.95 million deaths.
The astounding statistics position antimicrobial resistance as a leading cause of death globally, surpassing the deaths caused by HIV/AIDS and malaria, illustrating the immense magnitude of the AMR health crisis currently grasping the world. Perhaps more worrying is that although this is the most comprehensive estimate to date of the global impact of AMR, there were potentially millions more deaths caused by antimicrobial resistance in 2019.
The Global Research on Antimicrobial Resistance (GRAM) report analysed 204 countries and territories and elucidated how hundreds of thousands of once easily preventable deaths now occur due to infections, such as lower respiratory and bloodstream infections, due to the bacteria that causes them now being resistant to treatment.
The GRAM report reinforces the urgent requirement to scale-up efforts to combat antimicrobial resistance, highlighting essential actions that policymakers must implement to avert further substantial deaths and protect health systems. These suggestions include optimising antibiotic use, greater action to monitor and control infections, and financing funding to develop novel antibiotics and treatment.
Professor Chris Murray, the co-author of the study from the Institute for Health Metrics and Evaluation at the University of Washington, USA, said: “These new data reveal the true scale of antimicrobial resistance worldwide, and are a clear signal that we must act now to combat the threat. Previous estimates had predicted 10 million annual deaths from antimicrobial resistance by 2050, but we now know for certain that we are already far closer to that figure than we thought. We need to leverage this data to course-correct action and drive innovation if we want to stay ahead in the race against antimicrobial resistance.”
The complete findings of the study are published in The Lancet.
Antimicrobial resistance under the microscope
Previous AMR studies have been conducted in several countries and regions and for a small number of pathogen-drug combinations in a wider range of locations; however, no estimates have analysed all locations and a broad range of pathogens and drug combinations until now.
The GRAM report estimated deaths attributed to 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. The researchers utilised statistical modelling to obtain estimates of the impact of AMR in all locations, including those with no data, using 471 million individual health records from systematic literature reviews, hospital systems, surveillance systems, and other data sources.
The researchers quantified disease burden in two ways: deaths caused directly by AMR (deaths that would not have occurred if the infections were drug-susceptible, making them more treatable), and deaths associated with AMR (where a drug-resistant infection was implicated in deaths, but resistant itself may or may not have been the direct cause). The deaths caused by an association with antimicrobial resistance were calculated for 204 countries and territories and reported for 21 global regions and seven super-regions.
The subsequent analysis illuminated that antimicrobial resistance was attributable to an estimated 1.27 million deaths globally and associated with an estimated 4.95 million deaths in 2019. In contrast, HIV/AIDS is estimated to have caused 860,000 and 640,000, respectively, in 2019.
The greatest impact on AMR disease burden was demonstrated in drug-resistance in lower respiratory infections, such as pneumonia, causing over 400,000 deaths and associated with more than 1.5 million deaths. Drug resistance in bloodstream infections, which can result in the life-threatening condition sepsis, caused 370,000 deaths, and was associated with nearly 1.5 million deaths. Drug resistance in intra-abdominal infections – predominantly caused by appendicitis – caused around 210,000 deaths and was associated with around 800,000.
AMR impacts on age and location
Although antimicrobial resistance is a threat to all age groups, young children were found to be at particularly high risk, with around 20% of deaths attributable to AMR occurring in children aged under five years.
Deaths that were caused directly by antimicrobial resistance were estimated to be highest in Sub-Saharan Africa and South Asia, at 24 deaths per 100,000 population and 22 deaths per 100,000 population, respectively. Moreover, antimicrobial resistance was associated with 99 deaths per 100,000 in Sub-Saharan Africa and 77 deaths per 100,000 in South Asia. In high-income countries, AMR directly caused 13 deaths per 100,000 and was associated with 56 deaths per 100,000.
Examining pathogens
For their study, the researchers analysed 23 pathogens, with drug resistance in a mere six of them (E. coli, S. aureus, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa), leading directly to 929,000 deaths and was associated with 3.57 million. One particular pathogen-drug combination – methicillin-resistant S. aureus (MRSA) – caused over 100,00 deaths in 2019, with a further six causing between 50,000 and 100,000 deaths.
Of all the pathogens, resistance to two classes of antibiotics that are commonly employed as the first line of defence against severe infections – fluoroquinolones and beta-lactam antibiotics – accounted for over an estimated 70% of deaths caused by antimicrobial resistance.
Furthermore, how these pathogens impacted health varied considerably based on location. For example, deaths attributable to AMR in Sub-Saharan Africa were mainly caused by S. pneumonia (16% of deaths) or K. pneumonia (20%), whereas around 50% of deaths caused by AMR in high-income countries were caused by S. aureus (26%) or E. coli (23%).
Professor Christiane Dolecek, the co-author of the study and GRAM scientific lead, based in Oxford University’s Centre for Tropical Medicine and Global Health and the Mahidol Oxford Tropical Medicine Research Unit (MORU), commented: “With resistance varying so substantially by country and region, improving the collection of data worldwide is essential to help us better track levels of resistance and equip clinicians and policymakers with the information they need to address the most pressing challenges posed by antimicrobial resistance. We identified serious data gaps in many low-income countries, emphasising a particular need to increase laboratory capacity and data collection in these locations.”
Study limitations
The researchers have expressed that there are some limitations to their study. For instance, the limited availability of data for some regions of the world, mainly in LMICs, potentially limits the accuracy of estimates in these locations as this required robust methodological assumptions to be made in the analysis. Amalgamating and standardising data from a plethora of sources also led to potential bias sources, such as misclassification of community- or hospital-acquired infections and inconsistency in the distinction between drug-resistant and susceptible infections. Finally, there is also the possibility of selection bias in passive surveillance systems, and hospital microbial data from LMICs may skew towards more urban populations or more severe disease.
Dr Ramanan Laxminarayan from the Center for Disease Dynamics, Economics & Policy (USA), who was not involved in the study, said: “From being an unrecognised and hidden problem, a clearer picture of the burden of AMR is finally emerging. Even the lower end of 911,000 deaths estimated by Murray and colleagues is higher than the number of deaths from HIV, which attracts close to $50bn each year. However, global spending on addressing AMR is probably much lower than that.
“This needs to change. Spending needs to be directed to preventing infections in the first place, making sure existing antibiotics are used appropriately and judiciously, and to bringing new antibiotics to market. Health and political leaders at local, national, and international levels need to take seriously the importance of addressing AMR and the challenge of poor access to affordable, effective antibiotics.”
