Public health burden of antimicrobial resistance in Europe
Authors: Evelina Tacconelli, Maria Diletta Pezzani
Journal: The Lancet Infectious Diseases (2018)

Antimicrobial resistance is one of the greatest challenges of the 21st century. Evaluation of the public health burden of antimicrobial resistance, which is needed to drive policy interventions, is done through estimates of clinical benchmarks (mainly morbidity and crude mortality) and economic indicators (direct costs, use of resources, and drug expenditures). Most of these estimates are restricted to high-income countries and retrieve data to fit the computation models from national surveillance of clinical samples, prevalence or incidence surveys, and retrospective cohorts.1Naylor NR Atun R Zhu N et al.Estimating the burden of antimicrobial resistance: a systematic literature review.Antimicrob Resist Infect Control. 2018; 7: 58Crossref PubMed Scopus (242) Google Scholar, 2Gandra S Barter D Laxminarayan R Economic burden of antibiotic resistance: how much do we really know?.Clin Microbiol Infect. 2014; 20: 973-980Summary Full Text Full Text PDF PubMed Scopus (153) Google Scholar The high heterogeneity of reporting of surveillance data and the paucity of estimates of the societal effects of antimicrobial resistance (such as reduced productivity due to illness) substantially underestimate the public health burden. Global estimates are therefore limited in terms of generalisability of results and predictive values.3de Kraker ME Stewardson AJ Harbarth S Will 10 million people die a year due to antimicrobial resistance by 2050?.PLoS Med. 2016; 13: e1002184Crossref PubMed Scopus (606) Google Scholar In The Lancet Infectious Diseases, Alessandro Cassini and colleagues4Cassini 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. 2018; (published online Nov 5.)http://dx.doi.org/10.1016/S1473-3099(18)30605-4Summary Full Text Full Text PDF Scopus (1369) Google Scholar measured the health burden of five types of antibiotic-resistant infection (invasive and non-invasive) caused by eight bacteria with 16 resistance patterns in the EU and European Economic Area (EAA). The estimates, presented as disability-adjusted life-years (DALYs), are shocking. The authors estimate that there were 671 689 (95% CI 583 148–763 966) cases of infections with antibiotic-resistant bacteria in 2015, of which 426 277 (63·5%) were associated with health care. These estimates correspond with an incidence of 131 (113–149) infections per 100 000 population and an attributable mortality of 6·44 (5·54–7·48) deaths per 100 000 population. The overall DALY rate is 170 per 100 000 population, which is similar to the combined burden of HIV, influenza, and tuberculosis in the same year in the EU and EAA. The burden has doubled since 2007 and is highest in infants (aged <1 year) and older people (aged ≥65 years), and for infections caused by colistin-resistant or carbapenem-resistant bacteria. The highest health burdens (>400 DALYs per 100 000 population) were in Italy (10 762 attributable deaths) and Greece (1627 attributable deaths). Evaluation of the burden of infectious diseases can be challenging because they occur at different time scales and are influenced by many factors (ie, demography, epidemiological setting, population ageing, and method of measurement). A comparative analysis of the burden of foodborne diseases, influenza, tuberculosis, and HIV infection in Europe showed how—by use of incidence, mortality, or DALY rates—the burden of each infection varied substantially.5Van Lier EA Havelaar A Disease burden of infectious diseases in Europe: a pilot study.Euro Surveill. 2007; 12: E3-E4Crossref PubMed Scopus (45) Google Scholar The only resistant infection currently included by the Global Burden of Disease study, which assesses and quantifies the effects of diseases on a global level, is tuberculosis caused by resistant Mycobacterium tuberculosis.6Hay SI Abajobir AA Abate KH et al.Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet. 2017; 390: 1260-1344Summary Full Text Full Text PDF PubMed Scopus (1305) Google Scholar Cassini and colleagues report the first attempt to quantify DALYs for other resistant infections.4Cassini 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. 2018; (published online Nov 5.)http://dx.doi.org/10.1016/S1473-3099(18)30605-4Summary Full Text Full Text PDF Scopus (1369) Google Scholar The tragic scenario depicted in the analysis demands some consideration of the method used. The model, as is typical for population-wide studies, required a high number of estimates. The European Antimicrobial Resistance Surveillance Network surveillance system is not a population-based survey and does not allow for stratification of population type and outcome; it only records invasive infections that are influenced by the propensity of sampling and country coverage. Data used in systematic reviews also have method-related limitations, heterogeneity in the definition of outcomes and duration of follow-up, and restricted analysis of confounders, which intrinsically reduce the validity of the disease models built on these data. Cassini and colleagues could not adjust their models for age-specific risks, co-infections, and appropriateness of therapy, which might affect the determination of patient outcomes. Regardless, their study adds to the evidence base on the burden of antimicrobial resistance and could have a crucial role in fighting such resistance on two major levels. First, it represents a good framework to drive improvements in data reporting in surveillance systems and contributes to the many European initiatives to homogenise surveillance systems.7Tacconelli E Sifakis F Harbarth S et al.Surveillance for control of antimicrobial resistance.Lancet Infect Dis. 2018; 18: e99-e106Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar Second, by providing for the first time DALY data for countries with a high burden of antimicrobial resistance, this study calls for increased political awareness of, and commitment to, antimicrobial resistance. Although the G7 and G20 nations pushed antimicrobial resistance up the global health agenda, in most of the EU and EEA countries, national plans still seem far from having implemented major actions. What needs to be done in countries with the highest burden? We cannot forget that local financial resources, culture, and health-care structure (which are not accounted for in the estimates by Cassini and colleagues) have an important role in the control of antimicrobial resistance. European countries have a heterogeneous organisation of health care, in terms of the number of patients with severe infection and long hospital stays, stewardship teams, or nurse-to-patient ratios, which affect the effectiveness of infection control and antibiotic policy interventions.8Laxminarayan R Duse A Wattal C et al.Antibiotic resistance—the need for global solutions.Lancet Infect Dis. 2013; 13: 1057-1098Summary Full Text Full Text PDF PubMed Scopus (2547) Google Scholar Notably, the two countries with the highest burden have developed national plans to reduce the burden of antimicrobial resistance (in November, 2017, for Italy and in October, 2010, for Greece).9Ministero della SalutePiano Nazionale di Contrasto dell'Antimicrobico-Resistenza (PNCAR) 2017–2020.http://www.salute.gov.it/imgs/C_17_pubblicazioni_2660_allegato.pdfDate: 2017Date accessed: October 23, 2018Google Scholar, 10Hellenic Center for Disease Control & PreventionAction Plan "Procrustes". Hellenic Center for Disease Control & Prevention, Thessaloniki2010https://bit.ly/2qnfB0dDate accessed: October 23, 2018Google Scholar Will these plans be the answer to the alarm raised by Cassini and colleagues? Surely not. The extension and severity of the current situation cannot be solved without a more centralised global approach and decisive role of the European Parliament. We speculate that such an approach could be achieved through different legal mechanisms, such as by clearly defining standards for antibiotic usage in hospitals and community, establishing an alert zone (eg, critical rate of resistance at which urgent actions are needed at the country level) for resistance to specific antibiotics in invasive infections, setting a minimum gold standard for infection control measures to be mandatorily applied, defining curricula for infection control and antibiotic stewardship to be compulsorily included in medical schools, and setting up appropriate indicators to monitor the implementation and effectiveness of interventions. Annual targets in national plans should be globally discussed, interconnected, and coordinated. When countries do not respect agreed targets, action should be taken. This approach follows the example of what has been used from the European Parliament to successfully fight air pollution and reduce the related public health burden.11European ParliamentFact sheets on the European Union: air and noise pollution.http://www.europarl.europa.eu/factsheets/en/sheet/75/air-and-noise-pollutionDate: 2018Date accessed: October 23, 2018Google Scholar If Member States can set gold standards for air composition, surely they can agree on gold standards for the prevention and treatment of infections due to resistant bacteria. Economic restrictions and cultural and geographical variability cannot be accepted as explanations for the impressive difference in deaths among European citizens reported by Cassini and colleagues. The results demand increased political commitment and dedicated resources. Tackling antimicrobial resistance is not a simple task and various international stakeholders have been working for many years to reduce this public health burden. Clearly it is not enough. We declare no competing interests. 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 analysisOur results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. Full-Text PDF Open Access