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Antimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.


The aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.


Between September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant (MRSA) and rectal carriage of vancomycin-resistant / (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.


A total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).


This first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.


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  1. Roca I, Akóva M, Baquero F, Carlet J, Cavaleri M, Coenen S, et al. The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015;6:22-9.  https://doi.org/10.1016/j.nmni.2015.02.007  PMID: 26029375 
  2. de Kraker MEA, Davey PG, Grundmann H, BURDEN study group. Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe. PLoS Med. 2011;8(10):e1001104.  https://doi.org/10.1371/journal.pmed.1001104  PMID: 22022233 
  3. Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006;42(Jan) Suppl 2;S82-9.  https://doi.org/10.1086/499406  PMID: 16355321 
  4. Jung E, Byun S, Lee H, Moon SY, Lee H. Vancomycin-resistant Enterococcus colonization in the intensive care unit: clinical outcomes and attributable costs of hospitalization. Am J Infect Control. 2014;42(10):1062-6.  https://doi.org/10.1016/j.ajic.2014.06.024  PMID: 25278394 
  5. O’Neill J. Tackling drug-resistant infections globally: final report and recommendations. Tackling drug-resistant infections globally: final report and recommendations. London: Wellcome Trust; May 2016. Available from: https://wellcomecollection.org/works/thvwsuba
  6. World Health Organization (WHO). Antimicrobial resistance: Global report on surveillance. Geneva: WHO; 2014. Available from: https://apps.who.int/iris/handle/10665/112642
  7. World Health Organization (WHO). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. Geneva: WHO; 2017. Available from: https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf
  8. European Centre for Disease Control and Prevention (ECDC). Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals. Stockholm: ECDC; 2013. Available from: https://www.ecdc.europa.eu/en/publications-data/point-prevalence-survey-healthcare-associated-infections-and-antimicrobial-use-4
  9. Ciccolini M, Donker T, Köck R, Mielke M, Hendrix R, Jurke A, et al. Infection prevention in a connected world: the case for a regional approach. Int J Med Microbiol. 2013;303(6-7):380-7.  https://doi.org/10.1016/j.ijmm.2013.02.003  PMID: 23499307 
  10. European Commission (EC). Eurobarometer Results Programme Germany-Netherlands. Brussels: EC; 2015. Available from: https://ec.europa.eu/regional_policy/sources/policy/cooperation/european-territorial/cross-border/eb_results/germany-the-netherlands.pdf
  11. Köck R, Siemer P, Esser J, Kampmeier S, Berends MS, Glasner C, et al. Defining multidrug resistance of Gram-negative bacteria in the Dutch-German border region-impact of national guidelines. Microorganisms. 2018;6(1):11-8.  https://doi.org/10.3390/microorganisms6010011  PMID: 29373498 
  12. European Commission. Directive 2011/24/EU of the European Parliament and of the Council of 9 March on the application of patients’ rights in cross-border healthcare. Official Journal of the European Union. Luxembourg: Publications Office of the European Union; 4.4.2011:L 88/46. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:088:0045:0065:EN:PDF
  13. Müller J, Voss A, Köck R, Sinha B, Rossen JW, Kaase M, et al. Cross-border comparison of the Dutch and German guidelines on multidrug-resistant Gram-negative microorganisms. Antimicrob Resist Infect Control. 2015;4(1):7-7.  https://doi.org/10.1186/s13756-015-0047-6  PMID: 25763183 
  14. World Health Organization (WHO). Multimorbidity: Technical Series on Safer Primary Care. Geneva: WHO; 2016. Licence: CC BY-NC-SA 3.0 IGO. Available from: https://apps.who.int/iris/handle/10665/252275
  15. Tahir H, López-Cortés LE, Kola A, Yahav D, Karch A, Xia H, et al. Relevance of intra-hospital patient movements for the spread of healthcare-associated infections within hospitals - a mathematical modeling study. PLOS Comput Biol. 2021;17(2):e1008600.  https://doi.org/10.1371/journal.pcbi.1008600  PMID: 33534784 
  16. Depasse B, Pauwels D, Somers Y, Vincent JL. A profile of European ICU nursing. Intensive Care Med. 1998;24(9):939-45.  https://doi.org/10.1007/s001340050693  PMID: 9803330 
  17. van Duijn PJ, Dautzenberg MJD, Oostdijk EAN. Recent trends in antibiotic resistance in European ICUs. Curr Opin Crit Care. 2011;17(6):658-65.  https://doi.org/10.1097/MCC.0b013e32834c9d87  PMID: 21986462 
  18. European Committee on Antimicrobial Susceptibility Testing (EUCAST). EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance – Version 2.0. Växjö, EUCAST; 2017. Available from: https://www.eucast.org/resistance_mechanisms
  19. Berends MS, Luz CF, Friedrich AW, Sinha BNM, Albers CJ, Glasner C. AMR - An R Package for Working with Antimicrobial Resistance Data. bioRxiv. 810622. Preprint.  https://doi.org/10.1101/810622 
  20. European Commission. Decision No 2119/98/EC of the European Parliament and of the Council of 24 September 1998 setting up a network for the epidemiological surveillance and control of communicable diseases in the Community. Official Journal of the European Union. Luxembourg: Publications Office of the European Union. 3.10.1998:L 268/1. Available from: https://eur-lex.europa.eu/resource.html?uri=cellar:293fab95-972a-4d0c-ba28-45d9055fe1a3.0008.02/DOC_1&format=PDF
  21. Robert Koch Institute (RKI). Ergänzung zur Empfehlung der KRINKO „Hygienemaß- nahmen bei Infektionen oder Besiedlung mit multiresistenten Gram- negativen Stäbchen“ (2012) im Zusammenhang mit der von EUCAST neu definierten Kategorie „I“ bei der Antibiotika-Resistenzbestimmung: Konsequenzen für die Definition von MRGN. [Supplement to the KRINKO recommendation "Hygiene measures in the event of infections or colonisation with multiresistant Gram-negative rods" (2012) in connection with the new category "I" defined by EUCAST in the determination of antibiotic resistance: Consequences for the definition of MRGNs]. Epidemiologisches Bulletin. Berlin: RKI; 2019. German. Available from: https://edoc.rki.de/handle/176904/5952
  22. Werkgroep Infectiepreventie (WIP). Ziekenhuizen Bijzonder resistente micro-organismen (BRMO). [Particularly resistant micro-organisms (BRMO)]. Bilthoven: RIVM; 2017. Dutch. Available from: https://www.rivm.nl/sites/default/files/2018-11/130424%20BRMO.pdf
  23. Jurke A, Köck R, Becker K, Thole S, Hendrix R, Rossen J, et al. Reduction of the nosocomial meticillin-resistant Staphylococcus aureus incidence density by a region-wide search and follow-strategy in forty German hospitals of the EUREGIO, 2009 to 2011. Euro Surveill. 2013;18(36):20579.  https://doi.org/10.2807/1560-7917.ES2013.18.36.20579  PMID: 24079380 
  24. Jurke A, Daniels-Haardt I, Silvis W, Berends MS, Glasner C, Becker K, et al. Changing epidemiology of meticillin-resistant Staphylococcus aureus in 42 hospitals in the Dutch-German border region, 2012 to 2016: results of the search-and-follow-policy. Euro Surveill. 2019;24(15).  https://doi.org/10.2807/1560-7917.ES.2019.24.15.1800244  PMID: 30994105 
  25. Alp E, Leblebicioglu H, Doganay M, Voss A. Infection control practice in countries with limited resources. Ann Clin Microbiol Antimicrob. 2011;10(1):36.  https://doi.org/10.1186/1476-0711-10-36  PMID: 22018286 
  26. Gysin DV, Cookson B, Saenz H, Dettenkofer M, Widmer AF, ESCMID Study Group for Nosocomial Infections (ESGNI). Variability in contact precautions to control the nosocomial spread of multi-drug resistant organisms in the endemic setting: a multinational cross-sectional survey. Antimicrob Resist Infect Control. 2018;7:81.  https://doi.org/10.1186/s13756-018-0366-5  PMID: 30002821 
  27. Keizer J, Braakman-Jansen LMA, Kampmeier S, Köck R, Al Naiemi N, Te Riet-Warning R, et al. Cross-border comparison of antimicrobial resistance (AMR) and AMR prevention measures: the healthcare workers’ perspective. Antimicrob Resist Infect Control. 2019;8(1):123.  https://doi.org/10.1186/s13756-019-0577-4  PMID: 31367344 
  28. Robert Koch Institute (RKI). Antimicrobial Resistance Surveillance (ARS), Germany. Berlin: RKI. [Accessed: 1 Sep 2020]. Available from: https://ars.rki.de
  29. Rijksinstituut voor Volksgezondheid en Milieu (RIVM). Infectieziekten Surveillance Informatie Systeem-Antibiotica Resistentie (ISIS-AR). [Infectious Disease Surveillance Information System Antibiotic Resistance (ISIS-AR)]. Bilthoven: RIVM. [Accessed: 1 Sep 2020]. Dutch. Available from: https://www.rivm.nl/isis-ar
  30. European Centre for Disease Prevention and Control (ECDC). Surveillance Atlas of Infectious Diseases. Stockholm: ECDC. [Accessed: 1 Sep 2020]. Available from: https://atlas.ecdc.europa.eu/public/index.aspx
  31. Köck R, Becker K, Idelevich EA, Jurke A, Glasner C, Hendrix R, et al. Prevention and control of multidrug-resistant bacteria in The Netherlands and Germany-the impact of healthcare structures. Int J Environ Res Public Health. 2020;17(7):2337.  https://doi.org/10.3390/ijerph17072337  PMID: 32235650 
  32. Harbarth S, Sax H, Gastmeier P. The preventable proportion of nosocomial infections: an overview of published reports. J Hosp Infect. 2003;54(4):258-66, quiz 321.  https://doi.org/10.1016/S0195-6701(03)00150-6  PMID: 12919755 
  33. Eber MR, Shardell M, Schweizer ML, Laxminarayan R, Perencevich EN. Seasonal and temperature-associated increases in gram-negative bacterial bloodstream infections among hospitalized patients. PLoS One. 2011;6(9):e25298.  https://doi.org/10.1371/journal.pone.0025298  PMID: 21966489 

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