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In 2019, the World Health Organization published the 21st Model list of Essential Medicines and updated the Access, Watch Reserve (AWaRe) antibiotics classification to improve metrics and indicators for antibiotic stewardship activities. Reserve antibiotics are regarded as last-resort treatment options.


We investigated hospital-sector consumption quantities and trends of Reserve group antibiotics in European Union/European Economic Area countries and the United Kingdom (EU/EEA/UK).


Hospital-sector antimicrobial consumption data for 2010–2018 were obtained from the European Centre for Disease Prevention and Control. Antibacterials’ consumption for systemic use (Anatomical Therapeutic Chemical classification (ATC) group J01) were included in the analysis and expressed as defined daily doses (DDD) per 1,000 inhabitants per day. We defined reserve antibiotics as per AWaRe classification and applied linear regression to analyse trends in consumption of reserve antibiotics throughout the study period.


EU/EEA/UK average hospital-sector reserve-antibiotic consumption increased from 0.017 to 0.050 DDD per 1,000 inhabitants per day over the study period (p = 0.002). This significant increase concerned 15 countries. In 2018, four antibiotics (tigecycline, colistin, linezolid and daptomycin) constituted 91% of the consumption. Both absolute and relative (% of total hospital sector) consumption of reserve antibiotics varied considerably (up to 42-fold) between countries (from 0.004 to 0.155 DDD per 1,000 inhabitants per day and from 0.2% to 9.3%, respectively).


An increasing trend in reserve antibiotic consumption was found in Europe. The substantial variation between countries may reflect the burden of infection with multidrug-resistant bacteria. Our results could guide national actions or optimisation of reserve antibiotic use.


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  1. Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014;14(1):13.  https://doi.org/10.1186/1471-2334-14-13  PMID: 24405683 
  2. Plachouras D, Kärki T, Hansen S, Hopkins S, Lyytikäinen O, Moro ML, et al. , The Point Prevalence Survey Study Group. Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017. Euro Surveill. 2018;23(46):1800393.  https://doi.org/10.2807/1560-7917.ES.23.46.1800393  PMID: 30458917 
  3. Suetens C, Latour K, Kärki T, Ricchizzi E, Kinross P, Moro ML, et al. , The Healthcare-Associated Infections Prevalence Study Group. Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two European point prevalence surveys, 2016 to 2017. Euro Surveill. 2018;23(46):1800516.  https://doi.org/10.2807/1560-7917.ES.2018.23.46.1800516  PMID: 30458912 
  4. European Centre for Disease Prevention and Control (ECDC). Antimicrobial resistance surveillance in Europe 2015. Stockholm: ECDC; 2017. Available from: https://www.ecdc.europa.eu/en/publications-data/antimicrobial-resistance-surveillance-europe-2015
  5. European Centre for Disease Prevention and Control (ECDC). Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals 2011-2012. Stockholm: ECDC; 2013. Available from: https://www.ecdc.europa.eu/en/publications-data/point-prevalence-survey-healthcare-associated-infections-and-antimicrobial-use-0
  6. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al. , Burden of AMR Collaborative Group. 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(1):56-66.  https://doi.org/10.1016/S1473-3099(18)30605-4  PMID: 30409683 
  7. Levy Hara G, Kanj SS, Pagani L, Abbo L, Endimiani A, Wertheim HFL, et al. Ten key points for the appropriate use of antibiotics in hospitalised patients: a consensus from the Antimicrobial Stewardship and Resistance Working Groups of the International Society of Chemotherapy. Int J Antimicrob Agents. 2016;48(3):239-46.  https://doi.org/10.1016/j.ijantimicag.2016.06.015  PMID: 27502752 
  8. Kelkar D, Galwankar S. State of the globe: antimicrobial stewardship guides rationale use of antimicrobials to enable faster cure and prevent drug resistance. J Glob Infect Dis. 2013;5(2):43-4.  https://doi.org/10.4103/0974-777X.112261  PMID: 23853429 
  9. World Health Organization (WHO). AWaRe. WHO Antibiotic categorisation. Geneva: WHO. [Accessed: 17 Jan 2020]. Available from: https://aware.essentialmeds.org/groups
  10. World Health Organisation (WHO). WHO model lists of essential medicines. Geneva: WHO; 2017. Available from: https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists
  11. World Health Organization (WHO). The 2019 WHO AWaRe classification of antibiotics for evaluation and monitoring of use. Geneva: WHO; 2019. Available from: https://apps.who.int/iris/handle/10665/327957
  12. Klein EY, Milkowska-Shibata M, Tseng KK, Sharland M, Gandra S, Pulcini C, et al. Assessment of WHO antibiotic consumption and access targets in 76 countries, 2000-15: an analysis of pharmaceutical sales data. Lancet Infect Dis. 2021;21(1):107-15.  https://doi.org/10.1016/S1473-3099(20)30332-7  PMID: 32717205 
  13. Robertson J, Iwamoto K, Hoxha I, Ghazaryan L, Abilova V, Cvijanovic A, et al. Antimicrobial medicines consumption in Eastern Europe and Central Asia - an updated cross-national study and assessment of quantitative metrics for policy action. Front Pharmacol. 2019;9:1156.  https://doi.org/10.3389/fphar.2018.01156  PMID: 30890943 
  14. Hsia Y, Lee BR, Versporten A, Yang Y, Bielicki J, Jackson C, et al. , GARPEC and Global-PPS networks. Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries. Lancet Glob Health. 2019;7(7):e861-71.  https://doi.org/10.1016/S2214-109X(19)30071-3  PMID: 31200888 
  15. Hsia Y, Sharland M, Jackson C, Wong ICK, Magrini N, Bielicki JA. Consumption of oral antibiotic formulations for young children according to the WHO Access, Watch, Reserve (AWaRe) antibiotic groups: an analysis of sales data from 70 middle-income and high-income countries. Lancet Infect Dis. 2019;19(1):67-75.  https://doi.org/10.1016/S1473-3099(18)30547-4  PMID: 30522834 
  16. McGettigan P, Roderick P, Kadam A, Pollock AM. Access, Watch, and Reserve antibiotics in India: challenges for WHO stewardship. Lancet Glob Health. 2017;5(11):e1075-6.  https://doi.org/10.1016/S2214-109X(17)30365-0  PMID: 29025629 
  17. Malik F, Figueras A. Analysis of the antimicrobial market in Pakistan: is it really necessary such a vast offering of ‘watch’ antimicrobials? Antibiotics (Basel). 2019;8(4):189.  https://doi.org/10.3390/antibiotics8040189  PMID: 31627344 
  18. Schweickert B, Feig M, Schneider M, Willrich N, Behnke M, Peña Diaz LA, et al. Antibiotic consumption in Germany: first data of a newly implemented web-based tool for local and national surveillance. J Antimicrob Chemother. 2018;73(12):3505-15.  https://doi.org/10.1093/jac/dky345  PMID: 30239728 
  19. European Centre for Disease Prevention and Control (ECDC). Antimicrobial consumption - Annual epidemiological report for 2016. Stockholm: ECDC; 2018. Available from: https://www.ecdc.europa.eu/en/publications-data/antimicrobial-consumption-annual-epidemiological-report-2016
  20. European Centre for Disease Prevention and Control (ECDC). Country overview of antimicrobial consumption. Stockholm: ECDC. [Accessed: 23 Oct 2021]. Available from: https://www.ecdc.europa.eu/en/antimicrobial-consumption/database/country-overview
  21. World Health Organization (WHO) Collaborating Centre for Drug Statistics Methodology. International language for drug utilization research ATC/DDD Index. Oslo: WHO Collaborating Centre for Drug Statistics Methodology; 2021. Available from: http://www.whocc.no
  22. Publications Office of the European Union (EU). The EU Vocabularies website. Luxembourg; Publications Office of the EU. [Accessed: 23 Oct 2021]. Available from: https://op.europa.eu/en/web/eu-vocabularies
  23. R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2020. Available from: https://www.R-project.org
  24. European Centre for Disease Prevention and Control (ECDC). ECDC Map Maker tool (EMMa). Stockholm: ECDC. Available from: https://www.ecdc.europa.eu/en/publications-data/ecdc-map-maker-tool-emma
  25. European Centre for Disease Prevention and Control (ECDC). Surveillance of antimicrobial resistance in Europe 2018. Stockholm: ECDC; 2019. Available from: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-resistance-europe-2018
  26. Adriaenssens N, Coenen S, Versporten A, Muller A, Minalu G, Faes C, et al. , ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe (1997-2009). J Antimicrob Chemother. 2011;66(Suppl 6):vi3-12.  https://doi.org/10.1093/jac/dkr190  PMID: 22096064 
  27. European Medicines Agency (EMA). Cubicin. Summary of product characteristics. Amsterdam: EMA; 2006. Available from: https://www.ema.europa.eu/en/documents/product-information/tygacil-epar-product-information_en.pdf
  28. Gilbert DN, Chambers HF, Eliopoulos GM, Saag MS, Pavia A. The Sanford Guide to antimicrobial therapy. (48th edition). Sperryville, VA, USA: Antimicrobial Therapy, Inc. 2018.
  29. European Centre for Disease Prevention and Control (ECDC). Data from the ECDC Surveillance Atlas - Antimicrobial resistance. Stockholm: ECDC. [Accessed: 23 Oct 2021]. Available from: https://ecdc.europa.eu/en/antimicrobial-resistance/surveillance-and-disease-data/data-ecdc
  30. MacLaren G, Spelman D. Polymyxins: An overview. UpToDate. [Accessed: 23 Oct 2021]. Available from: https://www.uptodate.com/contents/polymyxins-an-overview?search=colistin&source=search_result&selectedTitle=2~58&usage_type=default&display_rank=1
  31. Giamarellou H. Epidemiology of infections caused by polymyxin-resistant pathogens. Int J Antimicrob Agents. 2016;48(6):614-21.  https://doi.org/10.1016/j.ijantimicag.2016.09.025  PMID: 27865627 
  32. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Guidance document on tigecycline dosing. Växjö: EUCAST; 2018. Available from: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/General_documents/Tigecycline_Guidance_document_20181223.pdf

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