In a recent article published within the Lancet journal, researchers quantified the worldwide bacterial antimicrobial resistance (AMR) burden to present deaths and disability-adjusted life-years (DALYs) attributable to and related to 23 pathogens, 12 major infectious syndromes, 18 drug categories, and 88 pathogen–drug mixtures.

They considered two counterfactual scenarios and used consistent methods to reach on the study estimates as they’d no clue of the extent to which susceptible or no infection would replace drug-resistant infections in a scenario when there was no drug resistance.

Study: Global burden of bacterial antimicrobial resistance in 2019: a scientific evaluation. Image Credit: Tatiana Shepeleva / Shutterstock

Background

Bacterial AMR, an emerging public health threat, is making antibiotic use futile or less effective against many common bacterial diseases affecting animals and humans. A United Kingdom (UK) government-commissioned review of AMR stated that it could claim 10 million lives annually by 2050.

The World Health Organization (WHO) and various other researchers have also raised that AMR spread is a pressing issue that needs immediate attention; if left unaddressed, rising AMR will make several bacterial pathogens highly fatal within the near future. The challenge is to collect current data on pathogen–drug mixtures contributing to actual bacterial AMR burden for all world regions, even those with minimal surveillance.

In response to the authors, studies have only reported AMR-related data for specific regions and a limited variety of pathogens and pathogen–drug mixtures. As an example, the USA Centers for Disease Control and Prevention (US-CDC) published a report in 2019 on AMR-related deaths for 18 AMR-related threats using surveillance data.

Similarly, Cassini et al. estimated the burden of eight and 16 pathogens and pathogen–drug mixtures, respectively, for the European region between 2007 and 2015. Despite the numerous contributions made by these studies to the sector of AMR, there may be an absence of comprehensive global estimates covering all locations, all pathogens, and all pathogen–drug mixtures contributing to the rising burden of bacterial AMR.

In regards to the study

In the current study, researchers used predictive statistical modeling to generate global estimates of bacterial AMR burden for all world locations, covering 204 countries for which they used all available data from the Global Burden of Diseases (GBD), Injuries, and Risk Aspects study. The GBD study collated age- and gender-specific estimates for 369 injuries and illnesses in 204 nations and territories between 1990 and 2019.

They retrieved data from published scientific literature, multisite research collaborations, clinical trials, research institutes based in low-income and middle-income countries (LMICs), private and non-private hospital records, diagnostic testing data, surveillance systems of pharmaceutical firms, global, national, and enhanced surveillance systems, and other relevant sources, encompassing 471 million (MN) patient records or isolates and seven,585 study-location years, which they gathered using varied strategies and used for study estimations.

The researchers modeled deaths and DALYs for 204 countries and territories to present cumulative estimates of AMR burden globally and for 21 GBD regions, including seven GBD super-regions.

For the primary counterfactual scenario, where susceptible infections substituted all drug-resistant infections, they estimated only deaths and DALYs directly as a consequence of AMR. For the second counterfactual scenario, where no infection substituted all drug-resistant infections, they estimated all deaths and DALYs related to resistant infections. Each estimates had different utilities; nevertheless, each could inform the event of intermediation strategies to control AMR spread.

The study approach comprised ten estimation steps inside five all-encompassing modeling components, each with varied data requirements; consequently, input data for every modeling component also varied.

Study findings

Substituting drug-resistant infections by no infections (first counterfactual scenario) and susceptible infections (second counterfactual scenario) would have saved 4.95MN and 1.27MN deaths, respectively, in 2019, implying that in 2019, the worldwide AMR burden related to drug-resistant infections for 88 pathogen–drug mixtures was ~4.95MN deaths (95% UI), of which drug resistance alone caused 1.27MN deaths. Furthermore, after ischaemic heart disease and stroke, AMR accounted for many deaths in 2019.

Moreover, the study evaluation revealed that AMR-related all-age death rates were highest in some LMICs, versus the common notion that the burden of bacterial AMR could be higher in high-resource settings with higher antibiotic consumption. Indeed, AMR is emerging as a more significant issue for a number of the world’s poorest countries. The authors noted the very best AMR-related death rates in sub-Saharan Africa and South Asia as a function of the prevalence of resistance and important lower respiratory, bloodstream, and intra-abdominal infections, in these regions.

The study also highlighted that in LMICs, there are other drivers of the upper AMR burden, like a scarcity of laboratory infrastructure for microbiological testing needed to narrow antibiotic use or make it more targeted. Amongst other aspects, counterfeit antibiotics, poor sanitation and hygiene, poor regulations on antibiotics use, etc., also drive resistance.

Further, the researchers identified six pathogens, E. coli, K. pneumoniae, S. pneumoniae, A. baumannii, S. aureus, and P. aeruginosa, who contributed most to the burden of AMR in 2019; they accounted for 73.4% (95% uncertainty interval) of deaths attributable to bacterial AMR. WHO has recognized all six as priority pathogens; nevertheless, except S. pneumoniae, targeted primarily through pneumococcal vaccination, none is the main target of worldwide health intervention programs.

Seven pathogen–drug mixtures caused greater than 50000 deaths, highlighting the necessity for expanding infection prevention and control (IPC) policies targeting the deadliest mixtures, bolstering vaccine and antibiotic development, and improving access to essential second-line antibiotics where needed. Moreover, resistance to β-lactam antibiotics, e.g., penicillins and cephalosporins, and fluoroquinolones accounted for >70% of deaths attributable to AMR across pathogens. These antibiotics are the primary line of empirical treatment for severe infections.

In 2017, the WHO published a priority list to tell research priorities related to latest antibiotics for pathogens with multidrug resistance that caused deadly infections. Nevertheless, this list covered only five of the seven pathogen–drug mixtures estimated to have caused essentially the most deaths in 2019; as an example, this list didn’t feature fluoroquinolone-resistant E. coli and meticillin-resistant S. aureus only as a “high” but not a “critical” priority.

Per study estimates, the magnitude of bacterial AMR as a worldwide public health issue is as much as human immunodeficiency virus (HIV) and malaria, perhaps, much higher. Moreover, the AMR pattern varied with geographical location, pathogens, and pathogen–drug mixtures. Thus, the regional estimates made on this study could help tailor local responses because the ‘One Size Suits All’ approach may not be appropriate.

Despite concerted data collection efforts, high-quality data on AMR was sparsely available for a lot of LMICs. Nevertheless, an improved scientific understanding of this rapidly emerging health threat ought to be the very best priority for global health policymakers.

Conclusions

The current study used major methodological innovations, two various AMR counterfactual scenarios, and comprehensive data to fetch novel insights into the worldwide AMR burden. Most significantly, it incorporated models tested and iterated over years during GBD study evaluation. So, when used collectively, these models provided an entire estimate of AMR burden with robust geographical coverage.

Further, the researchers compared findings with other causes of death, offering much-needed context on the size of the burden of this rapidly growing public health problem. The study evaluation confirmed that bacterial AMR posed the most important threat to human health in sub-Saharan Africa and South Asia, involved a various set of pathogens, and is exceptionally high for multiple essential antibiotic classes, including β-lactams and fluoroquinolones.

Moreover, efforts to construct and enhance laboratory infrastructure and bolster national & global AMR plans of motion are essential to addressing the universal AMR burden. Future studies also needs to evaluate the indirect effects of AMR, akin to its effect on the prophylaxis of infections in organ transplant recipients.

In the longer term, the study estimates could inform treatment guidelines against many predominant bacterial pathogens for a given infectious syndrome, which, together with estimates of pathogen–drug burden, could inform their treatment guidelines customized for a particular location.