The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis
Tomislav Meštrović, Gisela Robles Aguilar, Lucien R Swetschinski, Kevin S Ikuta, Authia P Gray, Nicole Davis Weaver, Chieh Han, Eve E Wool, Anna Gershberg Hayoon, Simon I Hay, Christiane Dolecek, Benn Sartorius, Christopher J L Murray, Isaac Yeboah Addo, Bright Opoku Ahinkorah, Ayman Ahmed, Mamoon A. Aldeyab, Kasim Allel, Robert Ancuceanu, Anayochukwu Edward Anyasodor, Marcel Ausloos, Fabio Barra, Akshaya Srikanth Bhagavathula, Dinesh Bhandari, Sonu Bhaskar, Natália Martins, Anna Dastiridou, Клара Докова, Eleonora Dubljanin, Oyewole Christopher Durojaiye, Adeniyi Francis Fagbamigbe, Simone Ferrero, Péter Gaál, Veer Bala Gupta, Vijai Kumar Gupta, Vivek Gupta, Claudiu Herţeliu, Salman Hussain, Irena Ilić, Milena Ilić, Elham Jamshidi, Tamás Joó, André Karch, Adnan Kısa, Sezer Kısa, Tomislav Kostyanev, Hmwe Hmwe Kyu, Judit Lám, Graciliana Lopes, Alexander G. Mathioudakis, Alexios‐Fotios A. Mentis, Irmina Maria Michałek, Mohammad Ali Moni, Catrin E. Moore, Francesk Mulita, Ionuţ Negoi, Ruxandra Irina Negoi, Tamás Palicz, Adrian Pană, João Perdigão, Ionela-Roxana Petcu, Navid Rabiee, David Laith Rawaf, Salman Rawaf, Murad Z. Shakhmardanov, Aziz Sheikh, Luís R. Silva, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Bogdan Socea, Andy Stergachis, Temenuga Stoeva, Chandra Datta Sumi, Arulmani Thiyagarajan, Marcos Roberto Tovani‐Palone, Metin Yeşiltepe, Sojib Bin Zaman, Mohsen Naghavi
Abstract
BACKGROUND: Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date. METHODS: We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. FINDINGS: We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR. INTERPRETATION: The 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. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.