A comprehensive analysis places antimicrobial resistance among leading causes of death globally

The most comprehensive estimate of the global impact of antimicrobial resistance thus far is published in The Lancet today. It reveals that more than 1.2 million people (and potentially millions more) around the world died in 2019 as a direct result of antibiotic-resistant bacterial infections – placing it among the leading causes of death.

Study: Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Image Credit: TheBlueHydrangea / Shutterstock

Antimicrobial resistance has emerged as one of the most pressing public health issues of the 21^st century that threatens the effective treatment and prevention of an ever-increasing range of infectious agents no longer susceptible to the drugs we have used to treat them.

This problem is especially relevant for bacteria; over several decades, bacterial pathogens that cause common and severe infections have developed resistance to basically every new antibiotic released to the market. Faced with this reality, the need for action to halt a developing global crisis in health care became very evident.

Nonetheless, for any policy interventions, there is a need for steadfast estimates to establish the magnitude of this threat. Global estimates of antimicrobial resistance, and especially how they relate to patient outcomes, were thus far rather limited in terms of generalizability.

This is one of the reasons why the Global Research on AntiMicrobial resistance (GRAM) Project has been launched, marking a strategic partnership between the Institute for Health Metrics and Evaluation (IHME) in the United States and the University of Oxford in the United Kingdom.

This project aimed to adapt and refine methodologies established in IHME’s ongoing Global Burden of Disease study in order to build an evidence base on bacterial antimicrobial resistance across the globe. A capstone paper that was just published in the journal The Lancet represents the most important deliverable of this project to date and sets the stage for further research in the field.

Estimating disease burden

The new GRAM report estimates deaths linked to 23 pathogens and 88 pathogen-drug combinations in 204 countries and territories in 2019. In addition, deaths caused by and associated with antimicrobial resistance were calculated and reported for 21 global regions and seven super-regions.

A multifaceted statistical modeling approach was utilized to generate estimates of the impact of antimicrobial resistance in all locations (including those with no actual data) by using 471 million data points and individual records collected from hospital systems, surveillance programs, systematic literature reviews and other data sources. This data was expansive, covering 185 of the 204 countries and territories globally.

The analysis was done in several defined steps; first, the researchers have estimated the number of deaths where infection played a role and then determined the fraction of infectious syndrome deaths due to a given bacteria. This was followed by calculating the percentage of bacteria resistant to an antibiotic of interest and estimating the excess risk of death or duration associated with this resistance.

Disease burden was estimated in two ways: deaths caused directly by antimicrobial resistance (i.e., deaths that would not have occurred had the infections been drug-susceptible and more treatable), and deaths associated with antimicrobial resistance (i.e., where a drug-resistant infection had been implicated in the death, but resistance itself may or may not have been the direct cause).

A substantial global threat

This new analysis showed how antimicrobial resistance was directly responsible for an estimated 1.27 million deaths globally in 2019, but also associated with an estimated 4.95 million deaths in the same year. For comparison purposes, global estimates suggest HIV/AIDS and malaria caused 860,000 and 640,000 deaths in 2019, respectively.

Furthermore, although antimicrobial resistance is a substantial threat to individuals of all ages, young children were recognized as a particularly high-risk group – with approximately one in five deaths attributable to resistant pathogens occurring in children younger than five years of age.

When specific infectious syndromes are concerned, antimicrobial resistance linked to lower respiratory infections had the greatest impact on disease burden, resulting in more than 400 thousand deaths and associated with more than 1.5 million deaths. This was closely followed by drug-resistant deaths in bloodstream infections and intra-abdominal infections. 

The results were commented exclusively for News Medical by a study co-author and IHME researcher Lucien Swetschinski. “Antimicrobial resistance is a global threat, from Western Europe, where the most advanced antibiotics are used, to Sub-Saharan Africa, where access to second-line therapies is limited,” he says.

“Though the pathogens of most concern and strategies needed to control the threat differ by location, the implication is clear: if left unchecked, antimicrobial resistance will jeopardize global health systems and cost us millions of lives,” he adds.

Informing our public health response

This study has shown that, by any metric, bacterial antimicrobial resistance represents a leading global health issue. Moreover, as all-age death rates linked to antimicrobial resistance were highest in certain low- and middle-income countries, this is evidently not only a global problem but a serious hazard for some of the poorest countries in the world.

“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”, emphasizes Professor Dr. Chris Murray, the Director of IHME and first author of the study, in the press release from The Lancet.

“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”, he adds.

Hence, identifying strategies that can reduce the burden of resistant bacterial pathogens (either those universally applicable or those tailored to a particular setting) is an urgent priority if we want to stay ahead in the race against antimicrobial resistance.

Among them are measures such as increased investment in new treatment solutions, optimized use of antimicrobials, as well as improved infection control and antibiotic stewardship. However, considering the burden of the problem, there will be a need for health and political leaders around the world to collaborate and understand the significance of addressing antimicrobial resistance.

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.