Estimating antimicrobial resistance burden in Europe—what are the next steps?

Abstract

Antimicrobial resistance (AMR) is a silent pandemic that is a major cause of death globally. However, many uncertainties still exist concerning the true extent of the AMR-associated clinical and public health burden. In The Lancet Public Health, Mohsen Naghavi and colleagues contribute to decreasing this uncertainty by presenting an important AMR burden analysis of the WHO European region,1European Antimicrobial Resistance CollaboratorsThe burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.Lancet Public Health. 2022; (published online Oct 13.)https://doi.org/10.1016/S2468-2667(22)00225-0Google Scholar following up on another recent report on the global AMR burden.2Antimicrobial Resistance CollaboratorsGlobal burden of bacterial antimicrobial resistance in 2019: a systematic analysis.Lancet. 2022; 399: 629-655Summary Full Text Full Text PDF PubMed Scopus (777) Google Scholar Their study overtakes previous AMR burden studies and provides the most comprehensive and detailed analysis of AMR burden in this region, covering 23 bacterial pathogens and 88 pathogen–drug combinations across 53 countries. Albeit with some counterintuitive, country-specific and pathogen-specific estimates, the tremendous efforts invested in this project are evident.Assessing AMR burden correctly is a taunting task; many previous studies generated heavily biased estimates.3de Kraker ME Stewardson AJ Harbarth S Will 10 million people die a year due to antimicrobial resistance by 2050?.PLoS Med. 2016; 13e1002184Crossref PubMed Scopus (565) Google Scholar Naghavi and colleagues applied an innovative methodological framework outlined by de Kraker and colleagues4de Kraker MEA Lipsitch M Burden of antimicrobial resistance: compared to what?.Epidemiol Rev. 2022; 43: 53-64Crossref PubMed Scopus (7) Google Scholar to estimate the burden of resistant infections compared with susceptible infection and no-infection counterfactual scenarios. This method served to predict the AMR burden that was possibly spared by interventions, acting both to replace resistant infections with susceptible ones (attributable burden) and to prevent infections in general (associated burden). The authors estimated 541 000 deaths (95% uncertainty interval 370 000–763 000) associated with AMR and 133 000 deaths (90 100–188 000) attributable to AMR in the WHO European region in 2019. This suggests that AMR-related infections, when compared with other major diseases, cause substantial adverse health outcomes throughout Europe, with similar attributable mortality as colon cancer, lung cancer, or liver cirrhosis.5Institute for Health Metrics and EvaluationGBD compare data visualization.http://vizhub.healthdata.org/gbd-compareDate: 2020Date accessed: September 1, 2022Google ScholarThe expanded scope of AMR burden estimation outside previously covered EU and European Economic Area countries6Cassini A Högberg LD Plachouras D et al.Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis.Lancet Infect Dis. 2019; 19: 56-66Summary Full Text Full Text PDF PubMed Scopus (1302) Google Scholar is of substantial importance. Novel estimates from eastern European countries will enable the perception of the full picture of AMR burden in the entire WHO European region, largely ignored so far. This study also provides country-specific estimates for death and disability-adjusted life-years per resistant pathogen, allowing inter-country comparisons useful for policy making.Despite methodological advances, modelling of AMR burden across different countries, populations, and health-care settings remains a challenging mission. Threats to the model validity are posed by possibly misleading underlying assumptions and misconceptions. A model's output is highly dependent on the quality and representativeness of the empirical input data. Predicted estimates should always be interpreted with caution, especially when sparse or poor quality empirical data are included. Consequently, the further need for consistent surveillance and collection of high-quality AMR data cannot be overstated. Unfortunately, the COVID-19 pandemic had negative implications on AMR surveillance and control.7Rodríguez-Baño J Rossolini GM Schultsz C et al.Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance.Trans R Soc Trop Med Hyg. 2021; 115: 1122-1129Crossref PubMed Scopus (34) Google Scholar, 8Tomczyk S Taylor A Brown A et al.Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: a global survey.J Antimicrob Chemother. 2021; 76: 3045-3058Crossref PubMed Scopus (29) Google Scholar Sustainable, high-quality surveillance networks, extending from microbiological profiling of resistance to include epidemiological and clinical data, can serve as a backbone to advance the knowledge on the true burden of AMR. Funding opportunities should be made accessible for research assessing the burden of AMR colonisation and infection, the effects of antimicrobial stewardship, and different antibiotic prescription habits on AMR spread. Research evaluating the burden of specific resistant-pathogen infection combinations, beyond the general AMR toll, is needed for development of pathogen-specific interventions, such as vaccines and monoclonal antibodies. More studies are also needed to better elucidate the adverse health-economic impact and indirect costs attributable to AMR. All these elements can bridge knowledge gaps and pave the way towards an exit strategy from this silent pandemic.Finally, Naghavi and colleagues' findings should encourage policy makers and clinicians throughout Europe to endorse and implement AMR control plans, as these were shown to be correlated with decreased country-level mortality rates associated with infection in the study, and they have proved successful in limiting the spread of resistance.9Schwaber MJ Carmeli Y An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae.Clin Infect Dis. 2014; 58: 697-703Crossref PubMed Scopus (164) Google Scholar Additionally, national policy makers and public health officials should use the predicted figures to map and analyse critical AMR threats in their countries and tailor specific action plans. In parallel, more attention should be given to implementing best practices of infection control and antibiotic stewardship in all healthcare settings to improve patient safety.It is important to bear in mind that AMR is a global threat, with Europe contributing only 10% of the global AMR burden.1European Antimicrobial Resistance CollaboratorsThe burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.Lancet Public Health. 2022; (published online Oct 13.)https://doi.org/10.1016/S2468-2667(22)00225-0Google Scholar The engagement of all regions around the world is needed to successfully face this challenge. The COVID-19 pandemic has taken the world a few steps further in the understanding of the value of collaboration during a pandemic crisis. Antimicrobial resistance (AMR) is a silent pandemic that is a major cause of death globally. However, many uncertainties still exist concerning the true extent of the AMR-associated clinical and public health burden. In The Lancet Public Health, Mohsen Naghavi and colleagues contribute to decreasing this uncertainty by presenting an important AMR burden analysis of the WHO European region,1European Antimicrobial Resistance CollaboratorsThe burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.Lancet Public Health. 2022; (published online Oct 13.)https://doi.org/10.1016/S2468-2667(22)00225-0Google Scholar following up on another recent report on the global AMR burden.2Antimicrobial Resistance CollaboratorsGlobal burden of bacterial antimicrobial resistance in 2019: a systematic analysis.Lancet. 2022; 399: 629-655Summary Full Text Full Text PDF PubMed Scopus (777) Google Scholar Their study overtakes previous AMR burden studies and provides the most comprehensive and detailed analysis of AMR burden in this region, covering 23 bacterial pathogens and 88 pathogen–drug combinations across 53 countries. Albeit with some counterintuitive, country-specific and pathogen-specific estimates, the tremendous efforts invested in this project are evident. Assessing AMR burden correctly is a taunting task; many previous studies generated heavily biased estimates.3de Kraker ME Stewardson AJ Harbarth S Will 10 million people die a year due to antimicrobial resistance by 2050?.PLoS Med. 2016; 13e1002184Crossref PubMed Scopus (565) Google Scholar Naghavi and colleagues applied an innovative methodological framework outlined by de Kraker and colleagues4de Kraker MEA Lipsitch M Burden of antimicrobial resistance: compared to what?.Epidemiol Rev. 2022; 43: 53-64Crossref PubMed Scopus (7) Google Scholar to estimate the burden of resistant infections compared with susceptible infection and no-infection counterfactual scenarios. This method served to predict the AMR burden that was possibly spared by interventions, acting both to replace resistant infections with susceptible ones (attributable burden) and to prevent infections in general (associated burden). The authors estimated 541 000 deaths (95% uncertainty interval 370 000–763 000) associated with AMR and 133 000 deaths (90 100–188 000) attributable to AMR in the WHO European region in 2019. This suggests that AMR-related infections, when compared with other major diseases, cause substantial adverse health outcomes throughout Europe, with similar attributable mortality as colon cancer, lung cancer, or liver cirrhosis.5Institute for Health Metrics and EvaluationGBD compare data visualization.http://vizhub.healthdata.org/gbd-compareDate: 2020Date accessed: September 1, 2022Google Scholar The expanded scope of AMR burden estimation outside previously covered EU and European Economic Area countries6Cassini A Högberg LD Plachouras D et al.Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis.Lancet Infect Dis. 2019; 19: 56-66Summary Full Text Full Text PDF PubMed Scopus (1302) Google Scholar is of substantial importance. Novel estimates from eastern European countries will enable the perception of the full picture of AMR burden in the entire WHO European region, largely ignored so far. This study also provides country-specific estimates for death and disability-adjusted life-years per resistant pathogen, allowing inter-country comparisons useful for policy making. Despite methodological advances, modelling of AMR burden across different countries, populations, and health-care settings remains a challenging mission. Threats to the model validity are posed by possibly misleading underlying assumptions and misconceptions. A model's output is highly dependent on the quality and representativeness of the empirical input data. Predicted estimates should always be interpreted with caution, especially when sparse or poor quality empirical data are included. Consequently, the further need for consistent surveillance and collection of high-quality AMR data cannot be overstated. Unfortunately, the COVID-19 pandemic had negative implications on AMR surveillance and control.7Rodríguez-Baño J Rossolini GM Schultsz C et al.Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance.Trans R Soc Trop Med Hyg. 2021; 115: 1122-1129Crossref PubMed Scopus (34) Google Scholar, 8Tomczyk S Taylor A Brown A et al.Impact of the COVID-19 pandemic on the surveillance, prevention and control of antimicrobial resistance: a global survey.J Antimicrob Chemother. 2021; 76: 3045-3058Crossref PubMed Scopus (29) Google Scholar Sustainable, high-quality surveillance networks, extending from microbiological profiling of resistance to include epidemiological and clinical data, can serve as a backbone to advance the knowledge on the true burden of AMR. Funding opportunities should be made accessible for research assessing the burden of AMR colonisation and infection, the effects of antimicrobial stewardship, and different antibiotic prescription habits on AMR spread. Research evaluating the burden of specific resistant-pathogen infection combinations, beyond the general AMR toll, is needed for development of pathogen-specific interventions, such as vaccines and monoclonal antibodies. More studies are also needed to better elucidate the adverse health-economic impact and indirect costs attributable to AMR. All these elements can bridge knowledge gaps and pave the way towards an exit strategy from this silent pandemic. Finally, Naghavi and colleagues' findings should encourage policy makers and clinicians throughout Europe to endorse and implement AMR control plans, as these were shown to be correlated with decreased country-level mortality rates associated with infection in the study, and they have proved successful in limiting the spread of resistance.9Schwaber MJ Carmeli Y An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae.Clin Infect Dis. 2014; 58: 697-703Crossref PubMed Scopus (164) Google Scholar Additionally, national policy makers and public health officials should use the predicted figures to map and analyse critical AMR threats in their countries and tailor specific action plans. In parallel, more attention should be given to implementing best practices of infection control and antibiotic stewardship in all healthcare settings to improve patient safety. It is important to bear in mind that AMR is a global threat, with Europe contributing only 10% of the global AMR burden.1European Antimicrobial Resistance CollaboratorsThe burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.Lancet Public Health. 2022; (published online Oct 13.)https://doi.org/10.1016/S2468-2667(22)00225-0Google Scholar The engagement of all regions around the world is needed to successfully face this challenge. The COVID-19 pandemic has taken the world a few steps further in the understanding of the value of collaboration during a pandemic crisis. NH-K received fundings from Innovative Medicines Initiative 2 Joint Undertaking (grant 101034420), ‘Predicting the Impact of Monoclonal Antibodies & Vaccines on Antimicrobial Resistance (PrIMAVeRa)’, with resources including in-kind contributions from companies in the European Federation of Pharmaceutical Industries and Associations. SH declares no competing interests. The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysisThe high levels of resistance for several important bacterial pathogens and pathogen–drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen–drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours. Full-Text PDF Open Access