Access the full text.
Sign up today, get DeepDyve free for 14 days.
I. Klare, Carola Fleige, Uta Geringer, Alexander Thürmer, J. Bender, N. Mutters, A. Mischnik, G. Werner (2015)Increased frequency of linezolid resistance among clinical Enterococcus faecium isolates from German hospital patients.
Journal of global antimicrobial resistance, 3 2
J. Bender, V. Cattoir, K. Hegstad, E. Sadowy, T. Coque, H. Westh, A. Hammerum, K. Schaffer, K. Burns, S. Murchan, C. Novais, Ana Freitas, L. Peixe, M. Grosso, A. Pantosti, G. Werner (2018)Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature.
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 40
E Tacconelli (2018)318
Lancet Infect Dis., 18
I. Klare, J. Bender, Carola Fleige, Nancy Kriebel, A. Hamprecht, S. Gatermann, G. Werner (2019)Comparison of VITEK® 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs
Journal of Antimicrobial Chemotherapy, 74
S. Harbarth, S. Cosgrove, Y. Carmeli (2002)Effects of Antibiotics on Nosocomial Epidemiology of Vancomycin-Resistant Enterococci
Antimicrobial Agents and Chemotherapy, 46
G Werner (2008)1182
J Antimicrob Chemother., 61
M Krull (2016)31
Antimicrob Resist Infect Control., 5
P. Lisotto, N. Couto, S. Rosema, M. Lokate, Xuewei Zhou, E. Bathoorn, H. Harmsen, A. Friedrich, J. Rossen, M. Chlebowicz-Fliss (2021)Molecular Characterisation of Vancomycin-Resistant Enterococcus faecium Isolates Belonging to the Lineage ST117/CT24 Causing Hospital Outbreaks
Frontiers in Microbiology, 12
J Top (2008)297
FEMS Immunol Med Microbiol., 52
S. Messler, I. Klare, F. Wappler, Guido Werner, Uwe Ligges, S. Sakka, Frauke Mattner (2019)Reduction of nosocomial bloodstream infections and nosocomial vancomycin-resistant Enterococcus faecium on an intensive care unit after introduction of antiseptic octenidine-based bathing.
The Journal of hospital infection, 101 3
N. Monteserin, E. Larson, E. Larson (2016)Temporal trends and risk factors for healthcare-associated vancomycin-resistant enterococci in adults.
The Journal of hospital infection, 94 3
S. Nys, N. Bruinsma, P. Filius, A. Bogaard, L. Hoffman, P. Terporten, A. Wildeboer-veloo, J. Degener, H. Endtz, E. Stobberingh (2005)Effect of hospitalization on the antibiotic resistance of fecal Enterococcus faecalis of surgical patients over time.
Microbial drug resistance, 11 2
R. Leclercq, E. Derlot, J. Duval, P. Courvalin (1988)Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium.
The New England journal of medicine, 319 3
I. Klare, J. Bender, G. Werner, U. Koppe, M. Sin, T. Eckmanns (2017)Eigenschaften, Häufigkeit und Verbreitung von VancomycinresistentenEnterokokken (VRE) in Deutschland
P. Gastmeier, C. Schröder, M. Behnke, E. Meyer, C. Geffers (2014)Dramatic increase in vancomycin-resistant enterococci in Germany.
The Journal of antimicrobial chemotherapy, 69 6
J. Bender, Julia Hermes, L. Zabel, S. Haller, N. Mürter, Hans-Peter Blank, G. Werner, Ingo Hüttner, T. Eckmanns (2022)Controlling an Unprecedented Outbreak with Vancomycin-Resistant Enterococcus faecium in Germany, October 2015 to November 2019
E. Tacconelli, E. Carrara, A. Savoldi, S. Harbarth, M. Mendelson, D. Monnet, C. Pulcini, G. Kahlmeter, J. Kluytmans, Y. Carmeli, M. Ouellette, K. Outterson, J. Patel, M. Cavaleri, E. Cox, C. Houchens, M. Grayson, P. Hansen, Nalini Singh, U. Theuretzbacher, N. Magrini, A. Aboderin, S. Al-Abri, Nordiah Jalil, N. Benzonana, S. Bhattacharya, A. Brink, F. Burkert, O. Cars, G. Cornaglia, O. Dyar, A. Friedrich, A. Gales, S. Gandra, C. Giske, D. Goff, H. Goossens, T. Gottlieb, M. Blanco, W. Hryniewicz, D. Kattula, Tim Jinks, S. Kanj, Lawrence Kerr, M. Kieny, Yang Kim, R. Kozlov, J. Labarca, R. Laxminarayan, K. Leder, L. Leibovici, G. Levy-Hara, Jasper Littman, S. Malhotra-Kumar, V. Manchanda, L. Moja, B. Ndoye, Angelo Pan, D. Paterson, M. Paul, Haibo Qiu, P. Ramón-Pardo, J. Rodríguez-Baño, M. Sanguinetti, S. Sengupta, M. Sharland, Massinissa Si-Mehand, L. Silver, W. Song, M. Steinbakk, Jens Thomsen, G. Thwaites, J. Meer, N. Kinh, S. Vega, M. Villegas, A. Wechsler-Fördös, Heiman Wertheim, E. Wesangula, N. Woodford, Fidan Yilmaz, Anna Zorzet (2017)Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis.
The Lancet. Infectious diseases, 18 3
C. Wendt, C. Krause, L. Xander, D. Löffler, H. Floss (1999)Prevalence of colonization with vancomycin-resistant enterococci in various population groups in Berlin, Germany.
The Journal of hospital infection, 42 3
A. Uttley, C. Collins, Jay Naidoo, R. George (1988)VANCOMYCIN-RESISTANT ENTEROCOCCI
The Lancet, 331
V. Weterings, Anita Oosten, Ellen Nieuwkoop, Jolande Nelson, A. Voss, B. Wintermans, J. Lieshout, J. Kluytmans, J. Veenemans (2021)Management of a hospital-wide vancomycin-resistant Enterococcus faecium outbreak in a Dutch general hospital, 2014–2017: successful control using a restrictive screening strategy
Antimicrobial Resistance and Infection Control, 10
Xuewei Zhou, M. Chlebowicz, E. Bathoorn, S. Rosema, N. Couto, M. Lokate, J. Arends, A. Friedrich, J. Rossen (2018)Elucidating vancomycin-resistant Enterococcus faecium outbreaks: the role of clonal spread and movement of mobile genetic elements
Journal of Antimicrobial Chemotherapy, 73
M García-Solache (2019)522
Clin Microbiol Rev., 32
C. Ford, Michaela Gazdik, B. Lopansri, B. Webb, B. Mitchell, J. Coombs, D. Hoda, F. Petersen (2017)Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic Stem Cell Transplantation Outcomes.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 23 2
Christian Wegner, N. Hübner, S. Gleich, U. Thalmaier, C. Krüger, A. Kramer (2013)One-day point prevalence of emerging bacterial pathogens in a nationwide sample of 62 German hospitals in 2012 and comparison with the results of the one-day point prevalence of 2010
GMS hygiene and infection control, 8
(2013)WIP-Richtlijn BRMO (Bijzonder Resistente Micro-Organismen) [ZKH]; RIVM: Bilthoven, The Nether-lands
L. Biehl, P. Higgins, Jannik Stemler, Meyke Gilles, S. Peter, D. Dörfel, W. Vogel, W. Kern, Hannah Gölz, H. Bertz, H. Rohde, E. Klupp, P. Schafhausen, J. Salmanton-García, M. Stecher, J. Wille, B. Liss, K. Xanthopoulou, J. Zweigner, H. Seifert, M. Vehreschild (2022)Impact of single-room contact precautions on acquisition and transmission of vancomycin-resistant enterococci on haematological and oncological wards, multicentre cohort-study, Germany, January−December 2016
G. Werner, T. Coque, A. Hammerum, R. Hope, W. Hryniewicz, A. Johnson, I. Klare, K. Kristinsson, R. Leclercq, C. Lester, M. Lillie, C. Novais, B. Olsson-liljequist, L. Peixe, E. Sadowy, G. Simonsen, J. Top, J. Vuopio‐Varkila, R. Willems, W. Witte, N. Woodford (2008)Emergence and spread of vancomycin resistance among enterococci in Europe.
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 13 47
H. Elsner, I. Sobottka, H. Feucht, E. Harps, C. Haun, D. Mack, R. Ganschow, R. Laufs, P. Kaulfers (2000)Nosocomial outbreak of vancomycin-resistant Enterococcus faecium at a German university pediatric hospital.
International journal of hygiene and environmental health, 203 2
DJ Austin, MJ Bonten, RA Weinstein, S Slaughter, RM Anderson (1999)Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs
Proc Natl Acad Sci U S A., 96
K. Gast, A. Oudheusden, J. Murk, J. Stohr, A. Buiting, J. Verweij (2021)Successful containment of two vancomycin-resistant Enterococcus faecium (VRE) outbreaks in a Dutch teaching hospital using environmental sampling and whole genome sequencing.
The Journal of hospital infection
M. Arthur, P. Courvalin (1993)Genetics and mechanisms of glycopeptide resistance in enterococci
Antimicrobial Agents and Chemotherapy, 37
B Schulte (2008)1131
Epidemiol Infect., 136
published maps and institutional affiliations
P. Chhatwal, E. Ebadi, F. Thol, C. Koenecke, G. Beutel, S. Ziesing, D. Schlüter, F. Bange, C. Baier (2020)Prospective infection surveillance and systematic screening for vancomycin-resistant enterococci in hematologic and oncologic patients - findings of a German tertiary care center.
Journal of global antimicrobial resistance
R. Evans (2014)European Centre for Disease Prevention and Control.
Nursing standard (Royal College of Nursing (Great Britain) : 1987), 29 9
B. Schulte, Alexandra Heininger, Ingo Autenrieth, Christiane Wolz (2007)Emergence of increasing linezolid-resistance in enterococci in a post-outbreak situation with vancomycin-resistant Enterococcus faecium
Epidemiology and Infection, 136
Brian Hollenbeck, L. Rice (2012)Intrinsic and acquired resistance mechanisms in enterococcus
KISS Krankenhaus-Infektions-Surveillance-System (Hospital Infection Surveillance System from Germany)
M. Scharlach, D. Wagner, J. Dreesman, M. Pulz (2011)[Antimicrobial resistance monitoring in Lower Saxony (ARMIN): first trends for MRSA, ESBL-producing Escherichia coli and VRE from 2006 to 2010].
Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)), 73 11
JK Bender (2018)25
Drug Resist Updat., 40
S. Borgmann, B. Schulte, C. Wolz, H. Gruber, G. Werner, C. Goerke, I. Klare, K. Beyser, Peter Heeg, I. Autenrieth (2007)Discrimination between epidemic and non-epidemic glycopeptide-resistant E. faecium in a post-outbreak situation.
The Journal of hospital infection, 67 1
C. Correa-Martínez, A. Jurke, Janne Schmitz, F. Schaumburg, S. Kampmeier, A. Mellmann (2022)Molecular Epidemiology of Vancomycin-Resistant Enterococci Bloodstream Infections in Germany: A Population-Based Prospective Longitudinal Study
E. Meyer, R. Ziegler, F. Mattner, F. Schwab, P. Gastmeier, M. Martin (2011)Increase of patients co-colonised or co-infected with methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium or extended-spectrum β-lactamase-producing Enterobacteriaceae
T. Kramer, C. Remschmidt, S. Werner, M. Behnke, F. Schwab, G. Werner, P. Gastmeier, R. Leistner (2018)The importance of adjusting for enterococcus species when assessing the burden of vancomycin resistance: a cohort study including over 1000 cases of enterococcal bloodstream infections
Antimicrobial Resistance and Infection Control, 7
BL Hollenbeck (2012)421
R Leclercq (1988)157
N Engl J Med., 319
J. Müller, A. Voss, R. Köck, B. Sinha, J. Rossen, M. Kaase, M. Mielke, I. Daniels-Haardt, A. Jurke, R. Hendrix, J. Kluytmans, M. Bergh, M. Pulz, J. Herrmann, W. Kern, C. Wendt, A. Friedrich (2015)Cross-border comparison of the Dutch and German guidelines on multidrug-resistant Gram-negative microorganisms
Antimicrobial Resistance and Infection Control, 4
S. Fridkin, J. Edwards, J. Courval, H. Hill, F. Tenover, Rachel Lawton, R. Gaynes, J. Mcgowan (2001)The Effect of Vancomycin and Third-Generation Cephalosporins on Prevalence of Vancomycin-Resistant Enterococci in 126 U.S. Adult Intensive Care Units
Annals of Internal Medicine, 135
C. Diazgranados, S. Zimmer, M. Klein, J. Jernigan (2005)Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 41 3
Sarah Jackson, A. Harris, L. Magder, K. Stafford, Kristie Johnson, L. Miller, D. Calfee, Kerri Thom (2019)Bacterial burden is associated with increased transmission to health care workers from patients colonized with vancomycin‐resistant Enterococcus
AJIC (American Journal of Infection Control), 47
C. Remschmidt, S. Schneider, E. Meyer, B. Schroeren-Boersch, P. Gastmeier, F. Schwab (2017)Surveillance of Antibiotic Use and Resistance in Intensive Care Units (SARI).
Deutsches Arzteblatt international, 114 50
M Arthur (1993)1563
Antimicrob Agents Chemother., 37
Lydia Sommer, T. Hackel, A. Hofmann, Julia Hoffmann, E. Hennebach, B. Köpke, W. Sydow, I. Ehrhard, I. Chaberny (2020)[Multi-Resistant Bacteria in Patients in Hospitals and Medical Practices as well as in Residents of Nursing Homes in Saxony - Results of a Prevalence Study 2017/2018].
Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))
G. Werner, T. Coque, C. Franz, E. Grohmann, K. Hegstad, L. Jensen, W. Schaik, K. Weaver (2013)Antibiotic resistant enterococci-tales of a drug resistance gene trafficker.
International journal of medical microbiology : IJMM, 303 6-7
Robert Weber, J. Bender, G. Werner, I. Noll, M. Sin, T. Eckmanns (2021)Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken (VRE) in Deutschland – Update 2019/2020
RIVM Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment in the Netherlands)
J. Keizer, L. Braakman-Jansen, S. Kampmeier, R. Köck, N. Naiemi, R. Riet-Warning, N. Jong, K. Becker, J. Gemert-Pijnen (2019)Cross-border comparison of antimicrobial resistance (AMR) and AMR prevention measures: the healthcare workers’ perspective
Antimicrobial Resistance and Infection Control, 8
Alessa Boschert, F. Arndt, A. Hamprecht, Martina Wolke, S. Walker (2023)Comparison of Five Different Selective Agar for the Detection of Vancomycin-Resistant Enterococcus faecium
C. Remschmidt, C. Schröder, M. Behnke, P. Gastmeier, C. Geffers, T. Kramer (2018)Continuous increase of vancomycin resistance in enterococci causing nosocomial infections in Germany − 10 years of surveillance
Antimicrobial Resistance and Infection Control, 7
G. Werner, S. Gfrörer, Carola Fleige, W. Witte, I. Klare (2008)Tigecycline-resistant Enterococcus faecalis strain isolated from a German intensive care unit patient.
The Journal of antimicrobial chemotherapy, 61 5
MS Gilmore (2013)10
Curr Opin Microbiol., 16
CD Ford (2017)340
Biol Blood Marrow Transpl., 23
J. Liese, L. Schüle, Philipp Oberhettinger, Leonie Tschörner, T. Nguyen, D. Dörfel, W. Vogel, M. Marschal, I. Autenrieth, Matthias Willmann, S. Peter (2019)Expansion of Vancomycin-Resistant Enterococcus faecium in an Academic Tertiary Hospital in Southwest Germany: a Large-Scale Whole-Genome-Based Outbreak Investigation
Antimicrobial Agents and Chemotherapy, 63
A. Kohlenberg, F. Schwab, E. Meyer, M. Behnke, C. Geffers, P. Gastmeier (2009)Regional trends in multidrug-resistant infections in German intensive care units: a real-time model for epidemiological monitoring and analysis.
The Journal of hospital infection, 73 3
Simon Brinkwirth, Sofie Martins, Olaniyi Ayobami, M. Feig, I. Noll, Benedikt Zacher, T. Eckmanns, G. Werner, N. Willrich, S. Haller (2022)Germany’s Burden of Disease of Bloodstream Infections Due to Vancomycin-Resistant Enterococcus faecium between 2015–2020
D. Austin, M. Bonten, R. Weinstein, S. Slaughter, R. Anderson (1999)Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs.
Proceedings of the National Academy of Sciences of the United States of America, 96 12
ML Faron (2016)2436
J Clin Microbiol., 54
Y Carmeli (2002)2223
Arch Intern Med., 162
The Dutch Working Party on Antibiotic Policy (SWAB) [October
F.N.J. Frakking, W.S. Bril, J.C. Sinnige, J.E. Klooster, B.A.W. Jong, E.J. Hannen, M. Tersmette (2018)Recommendations for the successful control of a large outbreak of vancomycin-resistant Enterococcus faecium in a non-endemic hospital setting.
The Journal of hospital infection, 100 4
Samenwerkingsverband Richtlijnen Infectiepreventie (SRI) [May, 2022]
C. Glasner, Matthijs Berends, K. Becker, J. Esser, J. Gieffers, A. Jurke, G. Kampinga, S. Kampmeier, R. Klont, R. Köck, L. Müller, Nashwan Naemi, A. Ott, G. Ruijs, K. Saris, A. Tami, A. Voss, K. Waar, J. Zeijl, A. Friedrich (2022)A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch–German cross-border region, 2017 to 2018: the importance of healthcare structures
J. Seo, Pyung-Whan Kim, J. Lee, Jae-Hoon Song, K. Peck, D. Chung, C. Kang, C. Ki, N. Lee (2011)Evaluation of PCR-based screening for vancomycin-resistant enterococci compared with a chromogenic agar-based culture method.
Journal of medical microbiology, 60 Pt 7
(2021)Signaleringsoverleg ziekenhuisinfecties en antimicrobiële resistentie (SO-ZI/AMR)
Nils-Olaf Huebner, K. Dittmann, V. Henck, Christian Wegner, A. Kramer (2016)Epidemiology of multidrug resistant bacterial organisms and Clostridium difficile in German hospitals in 2014: Results from a nationwide one-day point prevalence of 329 German hospitals
BMC Infectious Diseases, 16
Bernd Neumann, J. Bender, B. Maier, Alice Wittig, Stephan Fuchs, D. Brockmann, T. Semmler, H. Einsele, S. Kraus, L. Wieler, U. Vogel, G. Werner (2020)Comprehensive integrated NGS-based surveillance and contact-network modeling unravels transmission dynamics of vancomycin-resistant enterococci in a high-risk population within a tertiary care hospital
PLoS ONE, 15
Aktuelle Daten und Informationen zu Infektionskrankheiten und Public Health
S. Borgmann, Doris Niklas, I. Klare, L. Zabel, P. Buchenau, I. Autenrieth, P. Heeg (2004)Two episodes of vancomycin-resistant Enterococcus faecium outbreaks caused by two genetically different clones in a newborn intensive care unit.
International journal of hygiene and environmental health, 207 4
M. Gilmore, F. Lebreton, W. Schaik (2013)Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era.
Current opinion in microbiology, 16 1
(2019)susceptibility testing in Enterococcus faecalis and E
H. Aardema, J. Arends, A. Smet, J. Zijlstra (2015)Burden of highly resistant microorganisms in a Dutch intensive care unit.
The Netherlands journal of medicine, 73 4
Isabella Gruber, U. Heudorf, G. Werner, Y. Pfeifer, C. Imirzalioglu, H. Ackermann, C. Brandt, S. Besier, T. Wichelhaus (2013)Multidrug-resistant bacteria in geriatric clinics, nursing homes, and ambulant care--prevalence and risk factors.
International journal of medical microbiology : IJMM, 303 8
Nils-Olaf Hübner, C. Wegner, S. Gleich (2015)Multiresistente Erreger (MRE) und C. difficile in Münchner Akutkliniken
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 58
LF van der Steen, MJ Bonten, E van Kregten, JJ Harssema-Poot, R Willems, CA Gaillard (2000)Vancomycin-resistant Enterococcus faecium outbreak in a nephrology ward
Ned Tijdschr Geneeskd, 144
S. Walker, Martina Wolke, G. Plum, Robert Weber, G. Werner, A. Hamprecht (2020)Failure of VITEK2 to reliably detect vanB- mediated vancomycin resistance in Enterococcus faecium
G Werner (2008)52
Euro Surveill., 13
TS Kramer (2018)133
Antimicrob Resist Infect Control., 7
V. Cattoir (2021)The multifaceted lifestyle of enterococci: genetic diversity, ecology and risks for public health.
Current opinion in microbiology, 65
CD Salgado (2003)690
Infect Control Hosp Epidemiol., 24
L. Steen, M. Bonten, E. Kregten, J. Harssema-Poot, R. Willems, C. Gaillard (2000)[Vancomycin-resistant Enterococcus faecium outbreak in a nephrology ward].
Nederlands tijdschrift voor geneeskunde, 144 53
C. Salgado, B. Farr (2003)Outcomes Associated With Vancomycin-Resistant Enterococci: A Meta-Analysis
Infection Control & Hospital Epidemiology, 24
(2015)Multidrug-resistant organisms and C. difficile in Munich acute-care clinics: results from a point prevalence study of clinical routine data
Michail Alevizakos, A. Gaitanidis, D. Nasioudis, Katerina Tori, M. Flokas, E. Mylonakis (2016)Colonization With Vancomycin-Resistant Enterococci and Risk for Bloodstream Infection Among Patients With Malignancy: A Systematic Review and Meta-Analysis
Open Forum Infectious Diseases, 4
D. Weinstock, M. Conlon, C. Iovino, Tanya Aubrey, C. Gudiol, E. Riedel, James Young, T. Kiehn, G. Zuccotti (2007)Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 13 5
I Klare (2015)128
J Glob Antimicrob Resist., 3
Robert Koch-Institut (2015)Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken (VRE) in Deutschland – Update 2013/2014
E. Mascini, A. Troelstra, M. Beitsma, H. Blok, K. Jalink, T. Hopmans, A. Fluit, R. Hené, R. Willems, J. Verhoef, M. Bonten (2006)Genotyping and preemptive isolation to control an outbreak of vancomycin-resistant Enterococcus faecium.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 42 6
M. Knoll, G. Daeschlein, J. Okpara-Hofmann, I. Klare, D. Wilhelms, H. Wolf, M. Borneff-Lipp (2005)Outbreak of Vancomycin-Resistant Enterococci (VRE) in a Hematological Oncology Ward and Hygienic Preventive Measures. A Long-Term Study
Oncology Research and Treatment, 28
C Remschmidt, S Schneider, E Meyer, B Schroeren-Boersch, P Gastmeier, F Schwab (2017)Surveillance of antibiotic use and resistance in intensive care units (SARI)
Dtsch Arztebl Int., 114
R. Köck, K. Becker, E. Idelevich, A. Jurke, C. Glasner, R. Hendrix, A. Friedrich (2020)Prevention and Control of Multidrug-Resistant Bacteria in The Netherlands and Germany—The Impact of Healthcare Structures
International Journal of Environmental Research and Public Health, 17
Mónica García-Solache, L. Rice (2019)The Enterococcus: a Model of Adaptability to Its Environment
Clinical Microbiology Reviews, 32
Nationales Referenzzentrum (NRZ) für Staphylokokken und Enterokok-ken
(2003)Zum Auftreten und zur Verbreitung glycopeptidresistenter Enterokokken-Update
J. Dik, B. Sinha, A. Friedrich, J. Lo-Ten-Foe, R. Hendrix, R. Köck, B. Bijker, M. Postma, M. Freitag, G. Glaeske, F. Hoffmann (2015)Cross-border comparison of antibiotic prescriptions among children and adolescents between the north of the Netherlands and the north-west of Germany
Antimicrobial Resistance and Infection Control, 5
V Cattoir (2021)73
Curr Opin Microbiol, 65
Ilona Trautmannsberger, L. Kolberg, M. Meyer-Buehn, J. Huebner, G. Werner, Robert Weber, Valerie Heselich, S. Schroepf, Hans-Georg Muench, U. Both (2022)Epidemiological and genetic characteristics of vancomycin-resistant Enterococcus faecium isolates in a University Children's Hospital in Germany: 2019 to 2020
Antimicrobial Resistance and Infection Control, 11
N. Braak, A. Ott, A. Belkum, J. Kluytmans, J. Koeleman, L. Spanjaard, A. Voss, A. Weersink, C. Vandenbroucke-Grauls, A. Buiting, H. Verbrugh, H. Endtz (2000)Prevalence and Determinants of Fecal Colonization with Vancomycin-Resistant Enterococcus in Hospitalized Patients in The Netherlands
Infection Control & Hospital Epidemiology, 21
K. Xanthopoulou, S. Peter, David Tobys, M. Behnke, Ariane Dinkelacker, Simone Eisenbeis, Jane Falgenhauer, L. Falgenhauer, Moritz Fritzenwanker, Hannah Gölz, G. Häcker, P. Higgins, C. Imirzalioglu, N. Käding, W. Kern, E. Kramme, A. Kola, A. Mischnik, S. Rieg, A. Rohde, J. Rupp, E. Tacconelli, M. Vehreschild, S. Walker, P. Gastmeier, H. Seifert, B. Bader, F. Foschi, M. Gillis, Catriona Hennelly, Nadine Hoffmann, F. Hölzl, A. Lengler, Dana Lenke, Luis Diaz, G. Peyerl-Hoffmann, G. Pilarski, Susanna Proske, Judith Schmiedel, Heike Spitznagel, Y. Stelzer, N. Thoma, J. Trauth, M. Vávra, Anna Weber, J. Wille (2020)Vancomycin-resistant Enterococcus faecium colonizing patients on hospital admission in Germany: prevalence and molecular epidemiology.
The Journal of antimicrobial chemotherapy
A. Kramer, Sylvia Ryll, Christian Wegner, L. Jatzwauk, W. Popp, N. Hübner (2011)One-day point prevalence of emerging bacterial pathogens in four secondary and five tertiary care German hospitals – results from a pilot study of the German Society for Hospital Hygiene (Deutsche Gesellschaft für Krankenhaushygiene, DGKH)
GMS Krankenhaushygiene interdisziplinär, 6
A. Heininger, S. Zimmermann, Carolin Bootsveld, S. Boutin, D. Nurjadi (2020)Low prevalence of combined linezolid- and vancomycin-resistant Enterococcus faecium from hospital admission screening in an endemic region in Germany.
Journal of global antimicrobial resistance
CA DiazGranados (2005)327
Clin Infect Dis., 41
Evangelos Kritsotakis, A. Christidou, M. Roumbelaki, Y. Tselentis, A. Gikas (2008)The dynamic relationship between antibiotic use and the incidence of vancomycin-resistant Enterococcus: time-series modelling of 7-year surveillance data in a tertiary-care hospital.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 14 8
(2022)Antimicrobial resistance in the EU/EEA (EARS-Net) Annual Epidemiological
SV Walker, M Wolke, G Plum, RE Weber, G Werner, A Hamprecht (2021)Failure of Vitek2 to reliably detect vanB-mediated vancomycin resistance in Enterococcus faecium
J Antimicrob Chemother., 76
Surveillance of Antimicrobial Consumption Network (ESAC-Net) -Distribution of antimicrobial consumption by antimicrobial group
Vancomycin susceptibility testing in Enterococcus faecalis and E. faecium using MIC gradient tests–a modified warning 21 May, 2019
Xuewei Zhou, S. García-Cobos, G. Ruijs, G. Kampinga, J. Arends, D. Borst, L. Möller, N. Holman, T. Schuurs, L. Coppenraet, J. Weel, J. Zeijl, R. Köck, J. Rossen, A. Friedrich (2017)Epidemiology of Extended-Spectrum β-Lactamase-Producing E. coli and Vancomycin-Resistant Enterococci in the Northern Dutch–German Cross-Border Region
Frontiers in Microbiology, 8
Mark Jones, Deborah Draghi, C. Thornsberry, J. Karlowsky, D. Sahm, R. Wenzel (2004)Emerging resistance among bacterial pathogens in the intensive care unit – a European and North American Surveillance study (2000–2002)
Annals of Clinical Microbiology and Antimicrobials, 3
F. Thiery (2020)Linked COVID-19 Data: Johns Hopkins University (JHU) and European Centre for Disease Prevention and Control (ECDC)
G. Werner, Bernd Neumann, Robert Weber, M. Kresken, C. Wendt, J. Bender (2020)Thirty years of VRE in Germany - "expect the unexpected": The view from the National Reference Centre for Staphylococci and Enterococci.
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 53
Empfehlung Krinko, Melanie Brunke, Rechtlicher Hinweis, Vorrangiges Ziel, Zielgruppe Empfehlung (2018)Hygienemaßnahmen zur Prävention der Infektion durch Enterokokken mit speziellen Antibiotikaresistenzen
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz, 61
NICU Neonatal intensive care unit
A. Tricco, Erin Lillie, W. Zarin, K. O’Brien, H. Colquhoun, D. Levac, D. Moher, M. Peters, T. Horsley, L. Weeks, S. Hempel, E. Akl, Christine Chang, J. McGowan, L. Stewart, L. Hartling, Adrian Aldcroft, Michael Wilson, C. Garritty, S. Lewin, C. Godfrey, M. Macdonald, Etienne Langlois, K. Soares-Weiser, J. Moriarty, T. Clifford, zge Tunalp, S. Straus (2018)PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation
Annals of Internal Medicine, 169
J. McKinnell, Danielle Kunz, E. Chamot, Mukesh Patel, Rhett Shirley, S. Moser, J. Baddley, P. Pappas, L. Miller (2012)Association between Vancomycin-Resistant Enterococci Bacteremia and Ceftriaxone Usage
Infection Control & Hospital Epidemiology, 33
MJ Bonten (2001)314
Lancet Infect Dis., 1
M. Faron, N. Ledeboer, B. Buchan (2016)Resistance Mechanisms, Epidemiology, and Approaches to Screening for Vancomycin-Resistant Enterococcus in the Health Care Setting
Journal of Clinical Microbiology, 54
Minh Bui, A. Rohde, F. Schwab, Nayana Märtin, Marina Kipnis, Anne-Cathérine Boldt, M. Behnke, Luisa Denkel, A. Kola, J. Zweigner, P. Gastmeier, M. Wiese-Posselt (2021)Prevalence and risk factors of colonisation with vancomycin-resistant Enterococci faecium upon admission to Germany’s largest university hospital
GMS Hygiene and Infection Control, 16
C. Remschmidt, M. Behnke, A. Kola, L. Diaz, A. Rohde, P. Gastmeier, F. Schwab (2017)The effect of antibiotic use on prevalence of nosocomial vancomycin-resistant enterococci- an ecologic study
Antimicrobial Resistance and Infection Control, 6
Y. Carmeli, G. Eliopoulos, E. Mozaffari, M. Samore (2002)Health and economic outcomes of vancomycin-resistant enterococci.
Archives of internal medicine, 162 19
N Monteserin (2016)236
J Hosp Infect., 94
I. Noll, T. Eckmanns (2013)ARS – Antibiotika-Resistenz-Surveillance in Deutschland
Krankenhaushygiene up2date, 08
KRINKO Kommission für Krankenhaushygiene und Infektionsprävention
Infectious Diseases Surveillance Information System for Antimicrobial Resistance (ISIS-AR)
Xuewei Zhou, R. Willems, A. Friedrich, J. Rossen, E. Bathoorn (2020)Enterococcus faecium: from microbiological insights to practical recommendations for infection control and diagnostics
Antimicrobial Resistance and Infection Control, 9
B. Liss, J. Vehreschild, O. Cornely, M. Hallek, G. Fätkenheuer, H. Wisplinghoff, H. Seifert, M. Vehreschild (2012)Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies
(2006)Vancomycin-resistente Enterokokken in deutschen Krankenhäusern
SS Jackson, AD Harris, LS Magder, KA Stafford, JK Johnson, LG Miller (2019)Bacterial burden is associated with increased transmission to health care workers from patients colonized with vancomycin-resistant Enterococcus
Am J Infect Control., 47
Lisa Gunnink, D. Arouri, F. Jolink, M. Lokate, Klaas Jonge, S. Kampmeier, C. Kreis, M. Raschke, Mirjam Kleinjan, J. Maaten, A. Friedrich, E. Bathoorn, C. Glasner (2021)Compliance to Screening Protocols for Multidrug-Resistant Microorganisms at the Emergency Departments of Two Academic Hospitals in the Dutch–German Cross-Border Region
Tropical Medicine and Infectious Disease, 6
C. Boeing, C. Correa-Martínez, F. Schuler, A. Mellmann, A. Karch, S. Kampmeier (2021)Development and Validation of a Tool for the Prediction of Vancomycin-Resistant Enterococci Colonization Persistence—the PREVENT Score
Microbiology Spectrum, 9
Marco Krull, I. Klare, B. Ross, R. Trenschel, D. Beelen, D. Todt, E. Steinmann, J. Buer, P. Rath, J. Steinmann (2016)Emergence of linezolid- and vancomycin-resistant Enterococcus faecium in a department for hematologic stem cell transplantation
Antimicrobial Resistance and Infection Control, 5
J. Top, R. Willems, M. Bonten (2008)Emergence of CC17 Enterococcus faecium: from commensal to hospital-adapted pathogen.
FEMS immunology and medical microbiology, 52 3
M. Bonten, R. Willems, R. Weinstein (2001)Vancomycin-resistant enterococci: why are they here, and where do they come from?
The Lancet. Infectious diseases, 1 5
H. Guiot, W. Peetermans, F. Sebens (2005)Isolation of vancomycin-resistant enterococci in haematologic patients
European Journal of Clinical Microbiology and Infectious Diseases, 10
AH Uttley (1988)57
G. Timmers, W. Zwet, I. Simoons-Smit, P. Savelkoul, H. Meester, C. Vandenbroucke-Grauls, P. Huijgens (2002)Outbreak of vancomycin‐resistant Enterococcus faecium in a haematology unit: risk factor assessment and successful control of the epidemic
British Journal of Haematology, 116
Report about consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands
M Knoll, G Daeschlein, J Okpara-Hofmann, I Klare, D Wilhelms, HH Wolf (2005)Outbreak of vancomycin-resistant enterococci (VRE) in a hematological oncology ward and hygienic preventive measures A long-term study
The rising prevalence of vancomycin-resistant enterococci ( VRE) is a matter of concern in hospital settings across Europe without a distinct geographical pattern. In this scoping review, we compared the epidemiology of vancomycin-resistant Enterococcus spp. in hospitals in the Netherlands and Germany, between 1991 and 2022. We searched PubMed and summarized the national antibiotic resistance surveillance data of the two countries. We included 46 studies and summarized national surveillance data from the NethMap in the Netherlands, the National Antimicrobial Resistance Surveillance database in Germany, and the EARS-Net data. In total, 12 studies were con- ducted in hospitals in the Netherlands, 32 were conducted in German hospitals, and an additional two studies were conducted in a cross-border setting. The most significant difference between the two countries was that studies in Germany showed an increasing trend in the prevalence of VRE in hospitals, and no such trend was observed in studies in the Netherlands. Furthermore, in both Dutch and German hospitals, it has been revealed that the molec- ular epidemiology of VREfm has shifted from a predominance of vanA towards vanB over the years. According to national surveillance reports, vancomycin resistance in Enterococcus faecium clinical isolates fluctuates below 1% in Dutch hospitals, whereas it follows an increasing trend in German hospitals (above 20%), as supported by indi- vidual studies. This review demonstrates that VRE is more frequently encountered in German than in Dutch hospitals and discusses the underlying factors for the difference in VRE occurrence in these two neighboring countries by com- paring differences in healthcare systems, infection prevention control (IPC) guidelines, and antibiotic use in the Neth- erlands and Germany. Keywords Vancomycin-resistant enterococci, VRE, Antibiotic resistance, Epidemiology, Prevalence, Dutch-German cross-border region, Germany, The Netherlands Corinna Glasner and Axel Hamprecht these authors contributed equally. *Correspondence: Corinna Glasner email@example.com Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 2 of 20 . Although Germany and the Netherlands have many Background common historical, cultural, and social values, they differ Enterococci are among the most common nosocomial in many aspects regarding healthcare. These differences pathogens in the world . The spread of multidrug- include amongst others the healthcare structure, antibi- resistant enterococci in healthcare, the majority attrib- otic prescription habits, and local and national infection uted to Enterococcus faecium, and their adaptation to prevention and control (IPC) guidelines for multidrug- the hospital environment have been of concern since the resistant microorganisms (MDRO) [25–27]. All these 1970s [1, 2]. aspects taken together may be the cause for the differ - Enterococci can acquire antibiotic resistance by spo- ences in VRE rates encountered in these two neighboring radic chromosomal mutations or exogenous gene countries [25, 27–29]. exchange, besides being intrinsically resistant to many Despite the available evidence for the difference in antibiotics such as cephalosporins, trimethoprim-sul- the prevalence of VRE in the Netherlands and Germany, famethoxazole, and lincosamides . High-level resist- there are no nationwide comparative studies detail- ance to aminoglycosides and resistance to ampicillin ing this situation to date. Therefore, this review aims to and glycopeptides are well-known examples of acquired describe the epidemiology of vancomycin-resistant Ente- antibiotic resistance in enterococci [3, 4]. The first case rococcus spp. by presenting the outbreaks, VRE coloniza- of vancomycin-resistant enterococci (VRE) was reported tion prevalence, and VRE proportions in clinical isolates in France in 1986; since then, it has emerged as a major in hospitals in Germany and the Netherlands based on cause of nosocomial infections worldwide [5–7]. Vanco- the literature and national and European surveillance mycin resistance has been attributed to the acquisition data. of gene clusters that alter the nature of peptidoglycan precursors; and to date, nine different gene clusters have Methods been identified : vanA, vanB, vanC, vanD, vanE, vanG, We performed a scoping review using PubMed to search vanL, vanM, vanN. However, vanA and vanB are the for publications in English, Dutch, and German provid- major circulating gene clusters in human VRE coloniza- ing data on VRE colonization and infection prevalence, tion and infections, both in Europe and worldwide [5, 9]. incidence, surveillance, and outbreaks in hospital set- Given the fact that VRE are resistant to first-line anti - tings in the Netherlands and Germany. The review was biotics in hospital settings, there are a limited number performed following the recommendations of PRISMA- of therapeutic options, such as linezolid, tigecycline, and ScR . We performed a peer-reviewed search strategy, daptomycin . However, increasing resistance to these executed on December 30, 2022. The search term (Addi - last-resort antibiotics has been reported [10–14]. There - tional file 1) was externally reviewed by a research librar- fore, prevention of VRE infections is crucial to avoid ian from the University of Groningen. The authors (CC treatment challenges . and MSB) independently searched and extracted data Over the past two decades, studies have provided infor- using a peer-reviewed search strategy to avoid missing mation on the burden of VRE infections in hospitals [5, any relevant studies. No inconsistencies were encoun- 16–20]. Compared to vancomycin-susceptible entero- tered with this strategy. The dataset is available in Addi - cocci (VSE) infections, VRE infections are associated tional file 2, and those who are interested can reach out with higher morbidity, cost of care, longer length of hos- to the corresponding author for any further inquiries. pital stay, and mortality [19, 21, 22]. Unsurprisingly, the The relevance of the publications was assessed and World Health Organization (WHO) included VRE as a included following a defined flowchart (Fig. 1). First, high-priority pathogen in its global list of important anti- inclusion was based on title and abstract reading. biotic-resistant bacteria in 2017 . Data from the Euro- Selected articles were then accessed in full text to deter- pean Antimicrobial Resistance Surveillance Network mine eligibility and extract the data. The reference lists (EARS-Net) justified the WHO’s decision by showing of eligible publications were screened for additional that the prevalence of VRE across Europe doubled from articles. The scientific publications had to meet all the 2015 to 2019 . According to this report, an increase following criteria for inclusion: reported data had to in vancomycin resistance was reported across Europe include the number of VRE isolates and/or cases, and due to the increasing prevalence of vancomycin-resistant studies had to be conducted in a hospital. The following E. faecium (VREfm) . Interestingly, two neighbor- data were extracted from the selected publications: the ing countries, Germany and the Netherlands, are at both first author’s name, country of origin, province of where ends of the scale of the proportion of VREfm in all inva- the study was conducted, time frame for conducting the sive E. faecium isolates according to EARS-Net (< 1% in study, study methodology (outbreak report, surveillance the Netherlands and 22.3% in Germany). The underlying report, prevalence/incidence study), hospital type, ward/ reasons for this difference are not yet fully understood C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 3 of 20 database established by the Robert Koch-Institute (RKI) in Germany and for both countries from EARS-Net data [31–33]. Results Study inclusion and characteristics The initial search yielded 156 potentially relevant pub - lications, 80 of which were excluded based on title and abstract reading (Fig. 1). A further 32 publications were excluded after full-text evaluation. The reference lists of the eligible studies were screened, and four additional studies were included. Ultimately, 46 publications were included (Figs. 1, 2). Of the selected publications, 12 were conducted in the Netherlands, and 32 in Germany. Two further studies were cross-border studies that included data from both countries. In total, there were one eco- logical, one pre-post study, one longitudinal study, four cohort studies, 14 outbreak reports, and 25 cross-sec- tional studies. Outbreaks due to vancomycin‑resistant E. faecium (VREfm) Of the 12 studies conducted in the Netherlands, eight Fig. 1 Summary of the literature search and selection process were outbreak reports (Table 1) [34–41]. Of the 32 Ger- man publications, six were outbreak reports (Table 2) [42–47]. All outbreaks in both countries were caused by ICU type, number of cases/samples involved in the study, VREfm. In three of eight outbreaks observed in Dutch the number and prevalence, incidence or proportion of hospitals and in four of six outbreaks observed in Ger- VRE, and presence of resistance genes when available. man hospitals, VREfm infections were reported along- In addition, the national surveillance data from side patients colonized with VREfm [34, 37, 40, 42, the two countries were reviewed by extracting infor- 45–47]. One common factor observed in these reports mation from NethMap in the Netherlands and the was that colonization played a pivotal role in the occur- National Antimicrobial Resistance Surveillance (ARS) rence of outbreaks in both countries. Year of Publication The Netherlands GermanyCross-border region Fig. 2 Publication dates of the included articles Number of articles 2022 Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 4 of 20 Table 1 Summary of the studies on VRE carried out in Dutch hospitals (1991–2021) Study Design Year Setting Patient Sample site Clinical Species Sample size Outcome Resistance gene population relevance (%) Outbreak Reports Timmers et al. Outbreak report 1999 1 university Hematology Anal, BSI Infection, coloni- E. faecium 287 isolates VRE isolates: 76 vanA (100%)  hospital ward zation patients: 24 (2 infections) preva- lence: 26.4% Van der Steen Outbreak report 2000 1 non-university Nephrology Rectal, fecal, Colonization E. faecium 91 patients Patients:8 preva- ND et al.  hospital ward urine lence: 19.8% Mascini et al.  Outbreak report 2000–2003 1 university ICU, wards Rectal Colonization E. faecium 183 patients Patients:27 ND hospital prevalence: 14.8% Frakking et al. Outbreak report 2012–2014 1 teaching ICU, wards Rectal, BSI Infection, coloni- E. faecium ND Patients: 242 (22 vanA (76%), vanB  hospital zation infections) preva- (13%) lence: 4.3% Zhou et al.  Outbreak report 2014 1 university Wards Rectal, fecal, Colonization E. faecium ND VRE isolates: 36 vanB (94%), hospital sputum, bile patients: 34 vanA + vanB (4%) Weterings et al. Outbreak report 2014–2017 1 general hos- ND Rectal Colonization E. faecium 158 patients Patients: 13 ND  pital prevalence: 8% Lisotto et al.  Outbreak report 2014, 2017 1 university Wards Rectal, fecal, bile, Infection, coloni- E. faecium ND VRE isolates: 39 vanB (100%) hospital pus, BSI zation (3 infections) Gast et al.  Outbreak report 2018 1 teaching ICU, oncology Rectal, urine Colonization E. faecium ND Patients: 19 vanB (100%) hospital ward Studies reporting on the prevalence of VRE colonization Guiot et al.  Cross-sectional 1991 1 university Hematology Fecal Colonization E. faecium, E. 70 patients Patients: 9 preva- ND hospital ward faecalis lence: 12.9% Van den Braak Cross-sectional 1995–1998 5 university, 4 ICU, hematol- Rectal, fecal Colonization E. faecium, E. 1112 patients Patients: 15 (E ND et al.  regional teach- ogy-oncology faecalis faecium, 11, E. ing hospitals ward faecalis, 4) preva- lence: 1.3% Nys et al.  Cohort 1999–2002 3 university Surgical wards Fecal Colonization E. faecalis 261 patients Patients: 3 preva- ND hospital lence: 1.1% Studies reporting the frequency of VRE among all clinical and screening cultures Aardema et al. Cross-sectional 2009–2010 1 university ICU ND Infection, coloni- ND 962 patients Patients: 3 preva- ND  hospital zation lence: 0.3% VRE isolates: number of detected isolates of VRE, patients: number of patients colonized/infected with VRE ICU: intensive care unit, ND: not determined, VRE: vancomycin-resistant enterococci C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 5 of 20 Table 2 Summary of the studies on VRE carried out in German hospitals and hospitals in the Dutch-German cross-border region (1999–2022) Study Design Year Setting Patient Sample site Clinical Species Sample size Outcome Resistance gene population relevance (%) Outbreak Reports Elsner et al.  Outbreak report 1993–1997 1 university Pediatric ICU/ ND Infection, colo- E. faecium ND Patients: 32 (5 vanA (100%) hospital wards nization infections) Knoll et al.  Outbreak report 1999–2001 1 university Hematology Urine, fecal, Colonization E. faecium 1124 patients Patients: 44 vanA (100%) hospital axilla prevalence: 3.9% Borgmann et al. Outbreak report 2001 1 university NICU Fecal Colonization E. faecium ND Patients: 24 vanA (100%)  hospital Borgmann et al. Outbreak report 2004–2005 1 university ICU, wards Rectal, fecal, Infection, colo- E. faecium ND Patients: 248 (94 vanA (90%)  hospital wound, organ nization infections) swabs Liese et al.  Outbreak report 2010–2016 1 university All hospital Rectal, fecal, Infection, colo- E. faecium ND VRE isolates*: vanB (78.5%), vanA hospital intraoperative nization 773 patients: 796 (21.5%) samples, ascites, (159 infections) aspirates, BSI Bender et al.  Outbreak report 2015–2019 2 hospitals ND Rectal, clinical Infection, colo- E. faecium ND Patients: 2905 vanB (98%), vanA specimen nization (127 infections) (2%) Studies reporting on the prevalence of VRE colonization Wendt et al.  Cross-sectional 1995 1 university, ICU, surgical- Rectal Colonization E. faecium, E. 552 isolates Prevalence: vanA (80%), vanB 1 community medical wards faecalis 8.63% (university (20%) hospital h), 1.77% (com- munity h) Gruber et al.  Cross-sectional 2006–2007 1 non-university Geriatric clinic Rectal Colonization E. faecium 46 patients Patients: 7 preva- ND hospital lence: 15.2% Liss et al.  Cross-sectional 2008–2009 1 university Hematology- Fecal Colonization ND 513 patients Patients: 51 ND hospital oncology prevalence: 9.9% Messler et al.  Pre-post 2012–2013 1 university Surgical ICU Rectal, clinical Colonization E. faecium 2485 patients Patients: 86. vanA (61%), vanB hospital specimen prevalence: 3.6% (39%) Neumann et al. Cohort 2014–2015 1 tertiary care Hematology- Rectal Colonization E. faecium 1606 patients Patients: 111 vanB (91%), vanA  hospital oncology prevalence: (9%) 23.8% Bui et al.  Cross-sectional 2014–2015 1 university Wards (exc. ICU) Rectal Colonization E. faecium 4013 patients Patients: 48. ND hospital prevalence: 1.2% Xanthopoulou Cross-sectional 2014–2018 6 university Wards (exc. ICU) Rectal Colonization E. faecium 16,350 patients Patients: 263; vanB (78.5%), et al.  hospitals prevalence: vanA (20.2%), 2014, 0.8%; 2015, vanA + vanB (1.2%) 1.2%; 2016, 1.3%; 2017, 1.5%; 2018, 2.6% Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 6 of 20 Table 2 (continued) Study Design Year Setting Patient Sample site Clinical Species Sample size Outcome Resistance gene population relevance (%) Biehl et al.  Cohort 2016 4 university Hematology- Rectal, fecal Colonization E. faecium, E. 2928 patients Patients: 176 (E. vanB (77.8%), vanA hospitals oncology wards faecalis faecium, 173; (22%) vanA + vanB E faecalis, 3). (0.2%) prevalence: 6% Sommer et al. Cross-sectional 2017–2018 25 hospitals All hospital Rectal, wound Colonization E. faecium 629 patients Prevalence: 5.7% ND  Heininger et al. Cross-sectional 2018 1 university High risk Rectal Colonization E. faecium 2572 patients Patients: 712 ND  hospital patients prevalence: at admission 27.7% Chhatwal et al. Cross-sectional 2018–2019 1 university Hematology, Rectal, anal, Colonization E. faecium 555 patients Patients: 132 vanB (93%), vanA  hospital oncology wards fecal prevalence: (7%) 23.8% Trautmanns- Cross-sectional 2019–2020 1 university chil- NICU, PICU, Rectal Colonization E. faecium 693 patients Patients: 33 vanB (54.5%), vanA berger et al.  dren’s hospital surgical-medical prevalence: 4.8% (45.5%) wards Studies reporting the proportion of VRE in nosocomial infections and the incidence of VREfm in BSIs Gastmeier et al. Cross-sectional 2007–2012 ICU-KISS, OP- ICU, surgical Rectal, BSI, SSI Infection, colo- E. faecium E. ND Nosocomial VRE ND  KISS, Pathogen- wards UTI nization faecalis infections: 2007– KISS 08, 79; 2009–10, 106; 2011–12, 14 proportion of VRE from 2007 to 2012: in SSI, 0.87% to 4.58%; in BSI, 4.91% to 12.99%; in UTI, 2.23% to 6.19% C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 7 of 20 Table 2 (continued) Study Design Year Setting Patient Sample site Clinical Species Sample size Outcome Resistance gene population relevance (%) Remschmidt Cross-sectional 2007–2016 ICU-KISS, OP-KISS ICU (857), surgi- BSI, SSI, UTI Infection E. faecium, E. ND VRE infec- ND et al.  cal wards (1119) faecalis tions: 2007–08, 79; 2009–10, 106; 2011–12, 143; 2013–14, 187; 2014–15, 318 propor- tion of VRE from 2007/2008 to 2015/2016: overall, 1.4% to 10%; in BSI, 5.9% to 16.7%; in UTI, 2.9% to 9.9%; in SSI, 0.9% to 5% Correa-Martinez, Longitudinal 2016–2019 31 microbiology ND BSI Infection E. faecium ND VRE isolates: 2016, vanA et al. laboratories 755 incidence (64.5%); 2017, per 100,000 vanB (68.8%); inhabitants: 2018, vanB 2016, 0.48; 2019, (83.1%); 2019, 1.48 vanB (74.7) Brinkwirth et al. Cross-sectional 2015–2020 ARS ND BSI Infection E. faecium ND VRE isolates: ND  3417 incidence per 100,000 inhabitants: 2015, 1.4%; 2020, 29% Studies reporting the frequency of VRE among all clinical and screening cultures Jones et al.  Cross-sectional 2000–2002 169 hospitals ICU ND Infection, colo- E. faecium E. 621,636 isolates Proportion of E. ND (surveillance) nization faecalis faecium, 4.8; proportion of E. faecalis, 0.3 Remschmidt Cohort 2001–2015 SARI (44 hospi- ICU (77) ND Infection, colo- E. faecium, E. 263,639 isolates ND ND et al.  tals) nization faecalis Kohlenberg et al. Cross-sectional 2005–2006 MDR-KISS ICU ICU (176) Rectal, clinical Infection, colo- E. faecium, E. 284,142 patients Patients: 301 ND  specimen nization faecalis incidence per 1000 patient days: 0.1 Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 8 of 20 Table 2 (continued) Study Design Year Setting Patient Sample site Clinical Species Sample size Outcome Resistance gene population relevance (%) Scharlach et al. Cross-sectional 2006–2010 ARMIN—9 labo- ND ND Infection, colo- E. faecium 6,672,431 VRE isolates: ND  ratories in Lower nization isolates 2006, 667; 2010, Saxony 2431 proportion of VRE: 2006, 13.6; 2010, 5.6% Meyer et al.  Cross-sectional 2007–2009 4 university All hospital ND Infection, colo- E. faecium 896,822 patients Patients: 2007, ND hospitals nization 159; 2008, 277; 2009, 423 incidence per 10.000 patients: 2007, 5; 2008, 9; 2009,14) Kramer et al.  Cross-sectional 2010 5 tertiary, 4 ICU, surgical- ND Infection, colo- E. faecium, E. 3411 patients Patients: 12 ND (point preva- secondary care medical wards nization faecalis prevalence: lence survey) hospitals 0.49% Huebner et al. Cross-sectional 2012 37 acute-care ICU, surgical- ND Infection, colo- E. faecium 7154 patients Prevalence: ND  (point preva- hospitals medical wards nization 0.38% lence survey) Wegner et al. Cross-sectional 2012 10 tertiary, 20 ICU, surgical- ND Infection, colo- E. faecium, E. 12,968 patients Prevalence: ND  (point preva- secondary, 26 medical wards nization faecalis 0.27% lence survey) primary care hospitals Huebner et al. Cross-sectional 2014 45 tertiary, 76 ICU, surgical- ND Infection, colo- E. faecium, E. 73,938 patients/ VRE isolates: ND  (point preva- secondary, 208 medical wards nization faecalis isolates 207 prevalence, lence survey) primary care 0.25% hospitals Remschmidt Ecologic 2014–2015 1 university ICU, surgical- Rectal, clinical Infection, colo- E. faecium, E. 204,054 patients Patients (n): 1430 ND et al.  hospital medical specimen nization faecalis prevalence: 0.7% and hematol- ogy-oncology wards VRE isolates: number of detected isolates of VRE, patients: number of patients diagnosed with VRE. *available ARMIN: Antimicrobial Resistance Monitoring in Lower Saxony, BSI: blood-stream infection, ICU: intensive care unit, KISS: Krankenhaus-Infektions-Surveillance System (German national nosocomial surveillance system), ND: not determined, NICU: neonatal intensive care unit, OP-KISS: data on surgical site infections, PICU: pediatric intensive care unit, SARI: the surveillance of antibiotic use and resistance in intensive care units, UTI: urinary tract infection, SSI: surgical site infection, VRE: vancomycin-resistant enterococci C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 9 of 20 Table 3 Summary of the studies on VRE carried out in hospitals in the Dutch-German cross-border region (2012–2018) Study Design Year Setting Patient population Sample site Clinical relevance Species Sample size Outcome Resistance gene (%) Studies reporting on the prevalence of VRE colonization Zhou et al.  Cross-sectional 2012–2013 2 university hospitals ICU, wards Rectal Colonization ND NL: 445, DE: 102 VRE isolates: NL, 6; NL: vanB isolates DE, 4 prevalence: (100%), DE: NL, 1.3%; DE, 3.9% vanB (75%) Glasner et al.  Cross-sectional 2017–2018 8 Dutch, 15 German ICU Rectal Colonization E. faecium NL: 1110, DE: 2035 VRE isolates: NL, 1; ND hospitals isolates DE, 55 prevalence: NL, 0.1%; DE, 2.7% VRE isolates: number of detected isolates of VRE, patients: number of patients diagnosed with VRE ICU: intensive care unit, ND: not determined, DE: Germany, NL: the Netherlands Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 10 of 20 Summary on the epidemiology of VRE between 2012 and 2013, the prevalence of VRE colo- Thirty-two studies reported prevalence or incidence of nization in the German hospital (3.9%) was three times VRE among inpatients: 17 studies reported the preva- higher than in the Dutch hospital (1.3%) . The differ - lence of VRE colonization, three studies reported the ence was even more significant in the study carried out in proportion of VRE in nosocomial infections, 11 studies 23 hospitals’ ICUs (8 Dutch and 15 German) in the cross- reported the frequency of VRE among all clinical and border region between 2017 and 2018: VRE colonization screening cultures, and one study reported both the prevalence was almost 30 times higher in the German proportion of VRE in nosocomial infections and the fre- hospitals (2.7%) than in the Dutch hospitals (0.1%) . quency of VRE among clinical and screening cultures. Table 1, Table 2 and Table 3, which provide detailed epi- Studies reporting the proportion of VRE in nosocomial demiological data, indicate whether the numbers pre- infections and the incidence of VREfm in bloodstream sented correspond to VRE isolates or to the total number infections (BSIs) of patients diagnosed with VRE. The studies that reported the proportion of nosoco - mial, invasive VRE were all conducted in German hos- Studies reporting on the prevalence of VRE colonization pitals and presented an increase in VRE infections in Of the 17 studies that reported on the prevalence of VRE Germany over the years (Table 2) [65–68]. Two studies colonization, three were from Dutch hospitals and 14 analyzed data from the German National Nosocomial were from German hospitals. One cohort study and two Surveillance System (KISS, Krankenhaus-Infektions-Sur- cross-sectional studies investigated VRE colonization in veillance-System, https:// www. nrz- hygie ne. de/ kiss/ kiss- different patient groups in Dutch hospitals (Table 1). In module) and reported the proportion of VRE (E. faecium the cohort study, the prevalence of vancomycin-resistant and E. faecalis) in nosocomial infections. The first study E. faecalis colonization was 1.1% in surgical patients from analyzed the proportion of VRE in nosocomial infections three university hospitals . In the cross-sectional in ICUs and surgical departments between 2007 and studies, the prevalence of VRE colonization (E. faeca- 2012 . This study found not only an increasing trend lis and E. faecium) was 12.9% in the study conducted in of VRE (from 2007 to 2012: in SSI, 0.87% to 4.58%; in BSI, hematology patients of the university hospital in Leiden 4.91% to 12.99%; in UTI, 2.23% to 6.19%) in Germany in 1991  and 1.3% in the study involving intensive in general, but also a diversity between federal states care and hematology-oncology patients from nine differ - including a “VRE belt” in the middle of the country, rang- ent hospitals between 1995 and 1998 . ing from the West (North Rhine-Westphalia) to East The prevalence of VRE colonization in different patient (Saxony) . The second study described a continuous groups was investigated in nine cross-sectional stud- increase in nosocomial infections caused by VRE in Ger- ies, two cohort studies and one pre-post study in Ger- man ICUs and surgical wards from 1.4% in 2007 to 10% man hospitals. The prevalence ranged between 1.2% and in 2016 . 27.7% (Table 2) [51–62]. All studies reported the preva- The remaining two studies reported the incidence den - lence of VREfm colonization, except for three studies, sity of VREfm in bloodstream infections (BSI). The first one that did not specify the species and the other two study was a prospective longitudinal study in 31 labora- that reported both E. faecalis and E. faecium [51–62]. tories in North Rhine-Westphalia, Germany . This The highest prevalence was reported in studies among study found an increase in the incidence density (per hematology-oncology patients (23.8%), geriatric patients 100,000 inhabitants) of VREfm BSI from 0.52 in 2016 to (15.2%), and patients at high risk (27.7%) for VREfm col- 1.48 in 2019 . The second study analyzed the ARS onization [52, 54, 58, 59]. The lowest VREfm colonization surveillance system, which reported an increasing esti- (1.2% and 1.6%) prevalence was reported in two hospital- mated incidence density (per 100,000 inhabitants) of wide studies, which did not include intensive care unit VREfm BSI from 1.4 in 2015 to 2.9 in 2020 across the (ICU) patients [55, 56]. One of these studies was carried country . out in six university hospitals throughout Germany and found an increase in VREfm colonization prevalence Studies reporting the frequency of VRE among all clinical (0.8% in 2014, 1.2% in 2015, 1.3% in 2016, 1.5% in 2017, and screening cultures 2.6% in 2018) in inpatients over the years between 2014 All 12 studies (one conducted in a Dutch hospital and 11 to 2018 . in German hospitals) analyzed microbiology data with- Two cross-border studies compared the prevalence of out distinguishing between VRE infection or VRE colo- VRE colonization among hospitalized patients (Table 3). nization. Unless otherwise stated, the reported numbers In one of the studies conducted at two university hospi- represent the combined rate of VRE in both E. faecium tals in the Northern Dutch-German cross-border region and E. faecalis isolates. The study conducted at the Dutch C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 11 of 20 hospital (University Hospital Groningen) was a cross- In the Netherlands, of the eight reported outbreaks, six sectional study, reporting a prevalence of 0.3% VRE in reported the vanA/B status of isolates. In an outbreak in ICU patients . 1999 at the university hospital in Amsterdam, all VREfm Of the 11 German studies, nine were cross-sectional isolates were vanA-positive , and in another outbreak studies, one was a cohort study, and one was an ecologic at a non-university hospital in Utrecht between 2012 and study (investigating the impact of antibiotic use on VRE 2014, the majority of the VREfm isolates were vanA-posi- prevalence). An international surveillance study, includ- tive . In contrast, two outbreaks at the university hos- ing data from 169 German hospitals between 2000 and pital in Groningen in 2014 and 2017 were predominantly 2002, reported a VRE prevalence of 4.8% for E. faecium caused by vanB-VREfm [39, 40]. Similarly, in an outbreak and 0.3% for E. faecalis  and a study that analyzed at a tertiary hospital in Tilburg in 2018, all VREfm iso- MDR-KISS data between 2005 and 2006 reported a VRE lates were vanB-positive . prevalence of 0.1% in ICU patients . The ecologic In Germany, all reported VREfm outbreaks provided study that was conducted at the university hospital Ber- molecular data. The outbreaks at the university pediatric lin in 2012 reported a VRE prevalence of 0.7% ; in a hospital in Hamburg (1993–1997), at the university hos- point prevalence study conducted in 37 acute-care hospi- pital in Halle (1999–2001), and at the university hospital tals in Munich in 2012 a VREfm prevalence of 0.38% was in Tübingen (2001) were all caused solely by vanA VRE recorded in inpatients, including ICU patients . [42–44]. In another outbreak at the university hospital Three of the cross-sectional studies reported an in Tübingen in 2004, most VREfm isolates were vanA- increasing incidence of VRE over several years. In one positive . In a hospital-wide outbreak at a university of the studies that was conducted at four university hos- hospital in south-west Germany in 2015  and in a pitals across different regions in Germany (East, North, VREfm outbreak in two regional hospitals in southern Southwest, Southeast), an increase in the incidence (with Germany between 2015 and 2019, vanB was most fre- rates rising from 5 to 9 to 14 per 10,000 patients) of quently detected . VREfm was observed between 2007 and 2009 . Two Apart from the above-mentioned outbreak reports, no studies that analyzed the data from KISS and the Surveil- other studies from the Netherlands reported molecular lance of Antibiotic use and Resistance in ICUs (SARI) data of VRE. However, a shift from vanA to vanB over project also recorded an increase in VRE in German time was also observed in German non-outbreak stud- hospitals [67, 75]. The incidence of VRE cases (per 100 ies (Table 2). In a cross-sectional study at two hospitals admitted patients) in ICUs rose from 0.11 in 2007 to 0.31 in Berlin in 1995  and another at the university hos- in 2012 , whereas the resistance density of VRE in pital in Cologne between 2012 and 2013, most isolates German ICUs increased from 0.1 in 2001 to 1.1 per 1000 were vanA-positive . In contrast, most studies after patient days in 2015 in the other study, which included 2013 reported a predominance of vanB, including a study the SARI cohort . In contrast, three nationwide one- at a tertiary care hospital in southern Germany (2014– day point prevalence studies conducted in 2010, 2012, 2015) , a cohort study at the university hospitals in and 2014 using the same study protocol but with differ - Cologne, Freiburg, Hamburg, and Tübingen (2016) , ent numbers of participating hospitals did not show an and a cross-sectional study at six university hospitals increase in VRE colonization or infection among hos- throughout Germany (2014–2018) . In a longitudinal pitalized patients [76–78]. In addition to these national study in 31 microbiology laboratories in North Rhine- studies, a regional study was conducted to identify Westphalia, vanA was predominant in 2016, while vanB regional trends of AMR in Lower Saxony. In this study, was most prevalent in 2017–2019 in VRE BSIs . Simi- the data of the Antimicrobial Resistance Monitoring larly, in a study in 2018–2019 at the university hospital in in Lower Saxony (ARMIN) project in the period 2006– Hannover  and another study in 2019 in Munich , 2010 were analyzed, and strikingly, this study reported a vanB was more frequent than vanA. decreasing proportion of VREfm cases within those years in Lower Saxony from 13.6% in 2006 to 5.6% in 2010 . VRE surveillance data reports on the national level Both countries have their own national antibiotic resist- ance surveillance systems, including VREfm, and both Molecular epidemiology of VRE over time submit their results to EARS-Net. Data from outbreaks in both Dutch and German hospi- tals revealed that the molecular epidemiology of VREfm The Netherlands causing outbreaks has changed from a predominance Microbiological data of all isolates from medical micro- of vanA towards vanB over the years (Table 1–2) [34, 37, biology laboratories in the Netherlands are collected in 39–47]. Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 12 of 20 the Infectious Diseases Surveillance Information System potential decrease in reporting due to the burden of the for Antimicrobial Resistance (ISIS-AR) . Based on pandemic, as reporting is voluntary. these data and in collaboration with the Dutch Work- There is currently no nationwide surveillance of the ing Group on Antibiotic Policy of the Dutch Society of molecular epidemiology of VRE in the Netherlands. Medical Microbiology, a SWAB/RIVM report (NethMap) Centrally collected national data on VREfm molecular has been published annually to monitor AMR since 2003 typing were available only between 2012 and 2018, and . Data regarding VRE from clinical isolates have been vanA was always more frequent than vanB during this available since 2003 in NethMap reports (Fig. 3). period . According to the NethMap reports, there was a signifi - cant increase (from 0.1–0.8% to 1.5%) in the proportion of vanB-positive VREfm in hospitals between 2008 and Germany 2011. This increase was attributed to VREfm outbreaks, Microbiological data of all isolates from participat- particularly occurring in hospitals in the northern region ing medical microbiology laboratories and hospitals in of the country . As Fig. 3 shows, numerous VREfm Germany are collected in the ARS database established outbreaks have been reported in the Netherlands over by the RKI since 2008 . Pre-2008 national data are the years. However, the proportion of VREfm in clini- available in so-called Epidemiology Bulletins, which cal isolates of E. faecium in hospitals remained below have been periodically published by the RKI. Accord- 1% and has not changed in the last decade. To manage ing to these reports, there was an increase in the num- and prevent large-scale outbreaks of AMR in healthcare ber of VREfm isolates observed in 2003 and 2004 (both facilities and contain its spread to other institutions at an screening and clinical samples) compared to the previ- early stage, the Early Warning and Intervention Meet- ous years . Following a short decrease in the follow- ing for Nosocomial Infections and Antimicrobial Resist- ing two years, numbers increased again in 2007 . ance (SO-ZI/AMR), was established in the Netherlands The ARS database, available since 2008, provides data in 2012 . Participating hospitals have voluntarily regarding the proportion (%) of VREfm in all E. faecium committed to the SO-ZI/AMR system, which includes isolates obtained from inpatient blood cultures (Fig. 4). reporting obligations and regular updates until the out- Since 2009 an overall increasing trend of the VREfm break is resolved. Of all VREfm outbreaks in the last dec- proportion could be observed. ade, the lowest numbers were recorded in 2020 and 2021. A National Reference Center (NRC) for staphylo- This decrease could potentially be influenced by multiple cocci and enterococci was assigned by RKI in 2012 . factors such as the implementation of enhanced infection According to the NRC, significantly more vanB-VREfm control measures during the COVID-19 pandemic or a than vanA-VREfm isolates were sent to the NRC for the 1999-2003 2012 2013-15 2015-17 2017 2018-20 2020 2021 vanA- vanB- 9 VREfm 23 VREfm 26 VREfm 13 VREfm 34 VREfm 5 VREfm 8 VREfm VREfm VREfm outbreaks outbreaks outbreaks outbreaks outbreaks outbreaks outbreaks outbreaks outbreaks 2004, 2011 2012 2008-2010 2015 2016 2017 2013-2015 2018-2020 2020 2021 VREfm: VREfm: VREfm: VREfm: VREfm: VREfm: VREfm: VREfm: VREfm: VREfm: sporadic 0.1-0.8% 1.5% <0.5% <1% <0.5% 1% 0.6% <1% VREF cases 0.9% 0.8% Fig. 3 Summary of the number of VREfm outbreaks (blue boxes) and VREfm proportion (orange boxes) in clinical isolates in Dutch hospitals between 2003 and 2021 (NethMap reports) . The data in the boxes represent the temporal distribution of VRE data over the years. (VREF: vancomycin resistant E. faecalis, VREfm: vancomycin- resistant E. faecium) C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 13 of 20 2008 2009 2010 2011 2012 2013 20142015201620172018201920202021 Year Fig. 4 VREfm as the proportion (%) of all E. faecium isolates from inpatients’ blood cultures between 2008 and 2021 in Germany (ARS-RKI Statistics) . ( VREfm: vancomycin- resistant E. faecium) first time in 2017, and the situation has remained the In this review, the studies from the two countries did same since then [87, 88]. not only differ in number but also in the type of design. While most of the studies in the Netherlands were out- EARS‑net break reports, cross-sectional prevalence studies were The national AMR data represented in EARS-Net are predominant in Germany. The larger number of cross- obtained from the RIVM and RKI in the Netherlands sectional prevalence studies in German hospitals may and Germany, respectively . In 2021, the popula- indicate that VRE is a more pertinent problem in Ger- tion coverage in the EARS-Net surveillance data was man than in Dutch hospitals. 68% for the Netherlands and 35% for Germany . Analysis of outbreak reports revealed that all out- Throughout the years, the coverage percentages have breaks in both countries were caused by VREfm. This remained relatively stable, with the Netherlands con- is not surprising because of the high tenacity of E. sistently having higher coverage compared to Germany faecium to survive in the hospital environment . . The Netherlands is among 13 out of 30 countries Although the rate of infections differed within and that have maintained a VRE rate below 5% in clinical between countries, colonization was a common cause E. faecium isolates over the course of several years. In of VREfm outbreaks in both countries. Studies on contrast, in Germany, the percentage increased con- prevalence or incidence of VRE varied considerably tinuously between 2016 (11.9%) and 2019 (26.3%) and depending on the patient population and time. Gener- surpassed the European average since 2017 (Fig. 5) . ally, high VRE prevalences were reported in high-risk Interestingly, this percentage (22.3%) decreased in 2020 wards such as haemato-oncology and geriatric wards in for the first time since 2014 . both countries [49, 52–54, 59]. This finding is consist - ent with previous studies, which have identified age and Discussion haemato-oncological malignancies as risk factors for Given the limited treatment options and increasing both VRE colonization and infection [94–96]. prevalence of VRE in Europe, VRE remains a severe The most prominent difference between the two problem in healthcare [5, 24]. Despite this overall countries was that the German studies showed an increase, large variations have been reported between increasing trend of VRE prevalence in German hospi- countries . To the best of our knowledge, we pro- tals, yet such a trend was not observed in the Dutch vide the first comparative overview of the epidemiology studies. It is important to acknowledge that the smaller of VRE in hospital settings in the Netherlands and Ger- number of Dutch studies restricts the ability to draw many, covering 102 million EU inhabitants, by review- conclusive observations regarding this matter. Cross- ing the literature and national surveillance data. border studies have also demonstrated this difference Resistant isolates, proportion (%) Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 14 of 20 Year Germany The Netherlands EU/EAA average Fig. 5 The percentage of VREfm in clinical (invasive) E. faecium isolates in the Netherlands and Germany between 2001 and 2021. EU/EAA average was only reported between 2013 and 2020. Data from the ECDC Surveillance Atlas  when applying the same screening strategy for hospital- in Dutch hospitals [28, 98]. Secondly, despite the high ized patients [63, 64]. This observation is supported by number of hospitalizations and longer hospital stays, the national data of both countries and EARS-Net data. German hospitals suffer more compared to Dutch hospi - EARS-Net data shows that the proportion of VREfm tals from a shortage of HCPs, resulting in understaffing, in clinical E. faecium isolates from patients with inva- particularly in nursing care . The interaction between sive infections has remained stable, with slight fluctua - patients and HCPs has a crucial role in VRE transmis- tions below 1% in the Netherlands over the past decade, sion, which may be one of the factors contributing to the while in Germany, it has risen to over 25% with an high VRE prevalence in German hospitals, due to the low increasing trend [24, 65]. nurse-to-patient ratio . In the following paragraphs, we will elaborate on some points that may explain the difference in epidemiology of VRE between these two neighboring countries. Infection control guidelines In addition to the differences in healthcare structure, Healthcare system there are also variations in the national German and The inherent differences in healthcare structures could Dutch IPC guidelines for the prevention of VRE in hos- serve as a primary explanation for this difference [25, 28]. pitals . The frequency of MDROs in hospitals could Both Germany and the Netherlands have well-established serve as an indicator of the effectiveness of IPC meas - healthcare systems, however, they differ in important ures. In Germany, the Commission for Hospital Hygiene aspects . Firstly, the density of inpatient care (num- and Infection Prevention (KRINKO, Kommission für ber of cases), the average length of hospital stay, and bed Krankenhaushygiene und Infektionsprävention), and occupancy rate were found to be significantly higher in in the Netherlands the Infection Prevention Working Germany-all factors that could increase the risk of VRE Group (WIP, Werkgroep Infectie Preventie, Samen- transmission through increased patient-to patient and werkingsverband Richtlijnen Infectiepreventie), issue patient-to-healthcare professional (HCP) contact . these national IPC guidelines [98, 100, 101]. In general, As the hospital environment is one of the key factors for while the application of IPC rules in the German guide- VRE transmission via surfaces, a high occupancy rate in line varies according to the epidemiological situation of hospitals would also facilitate the spread of VRE . In the hospital and region, there is no such exception in the addition, high bed occupancy rates result in fewer sin- Dutch guideline. The KRINKO guidelines primarily focus gle rooms available to isolate patients with VRE, making on prevention of infections requiring antibiotic therapy, it challenging to implement adequate IPC rules in Ger- classifying patient groups according to their risk of evolv- man hospitals . In contrast, even pre-emptive isola- ing VRE infection, whereas the WIP guidelines recom- tion is implemented for at risk patients upon admission mend a search and detect strategy. For instance, in the Resistant isolates, percentage (%) C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 15 of 20 WIP guidelines, there is no distinction between high-risk contributing to variations in the reported number of VRE wards and normal-care wards in VRE screening, whereas cases between the two countries. the KRINKO guidelines recommend VRE screening only on patients in high-risk wards. The management of VRE Commonalities carriers also differs in the two guidelines; the WIP guide - Even though the general development in VRE epide- lines recommend contact isolation without exception, miology in the Netherlands and Germany differed sub - but the KRINKO guidelines leaves the decision to clini- stantially in the last decades, two common trends have cians, based on the patient’s risk assessment. Thus, the emerged. The first trend is the potential impact of the stricter infection control rules applied in Dutch hospitals COVID-19 pandemic on VRE epidemiology. Data from could contribute to the lower prevalence of VRE. EARS-Net reports for 2020 and 2021 indicate that the number of VRE outbreaks and the proportion of VRE among all E. faecium isolates from clinical isolates have Antibiotic consumption decreased in both countries compared to the previous In addition to well-established IPC measures and the year . This decline could be due to an increased level of compliance with these measures, appropriate awareness of IPC measures among healthcare profes- use of antibiotics plays a significant role in preventing sionals and the disruption of healthcare services due to colonization with VRE and, hence, infection . For the COVID-19 pandemic. However, it is also possible instance, the use of broad-spectrum cephalosporins has that deprioritization of AMR surveillance in hospitals been linked to an increased VRE prevalence, both by and less engagement to national surveillance systems facilitating the acquisition of VRE and by exerting high may have led to an underestimation of actual situation. selective pressure on the gastrointestinal flora [103–106]. The second trend is the change in the molecular epi - Data from the European Surveillance of Antimicrobial demiology of VRE over time. In Germany, molecular Consumption Network (ESAC-Net) from 1997 to 2020 typing analyses have been performed on all entero- indicate that the use of broad-spectrum cephalosporins cocci submitted to the NRC, while in the Netherlands, in the community in Germany was higher than in the such analyses were only available for centrally collected Netherlands . Given this difference in the use of this enterococci between 2012 and 2018. Apart from the particular antibiotic group between the two countries, it national surveillance data, identified publications illus - is possible that this will also have an impact on the differ - trated that vanB began to be reported as the leading ence in VRE prevalence observed between them. cluster both in the Netherlands and in Germany, since 2014 [39–41, 54, 56, 59]. This shift in molecular epide - miology has led to debate about whether this change Diagnostics is a result of an actual rise in the circulation of vanB Apart from the aforementioned differences that have strains or limitations in the detection of vanB-VRE in been outlined between the Netherlands and Germany, the laboratory . Comparative studies have revealed it is important to consider that variations in the diag- that gradient strip assays and automated antibiotic sus- nostic laboratory protocols, guidelines, and availabil- ceptibility testing methods commonly used in the rou- ity of resources for detecting VRE may also play a role tine laboratory setting fail to detect vanB-mediated in influencing the reported VRE cases in each country vancomycin resistance [112, 113]. EUCAST has also . Variations in diagnostic protocols, including sam- acknowledged these issues and revised recommenda- ple collection, culturing techniques, and antimicrobial tions to reduce the error rate in detecting vanB-VRE susceptibility testing, can impact VRE detection. For . example, variances in media and selective agents used for VRE isolation affect sensitivity and specificity . Differences in the adoption and implementation of sur - Limitations veillance guidelines can also affect VRE detection and There are limitations to this study. Firstly, a meta-analysis reporting, particularly in screening frequency and extent was not possible due to the heterogeneity in study design, for VRE colonization in specific patient populations [98, patient populations, timeframes, and outcome definitions 100]. Additionally, the availability of resources (financial, across the publications. Secondly, comparing the national technological, and human) plays a significant role in a surveillance data might cause biases owing to the chang- laboratory’s capacity to detect VRE, with advanced tech- ing number of participating hospitals and laboratories nologies like PCR assays improving sensitivity and speed and different data collection compliance in the two coun - . These factors can potentially impact the accuracy tries. Thirdly, a comprehensive comparison of implemen - and thoroughness of VRE detection and reporting, thus tation and compliance to the national IPC guidelines at Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 16 of 20 Acknowledgements the hospital level was beyond the scope of the current We gratefully acknowledge the support and cooperation with the CHARE- study, disallowing us to compare the real-life records of GD (Comparison of healthcare structures, processes and outcomes in the hospital practice. Northern German and Dutch cross-border region) Study Group. This study was conducted in partnership with the CrossBorder Institute of Healthcare Systems and Prevention (CBI), Groningen/Oldenburg. Conclusion In conclusion, this review has provided an overview of the Author contributions CC, AH and CG designed the study. CC and MSB performed literature epidemiology of VRE in the hospital setting in the Nether- screening independently, study selection and data extraction. CC wrote the lands and Germany, highlighting the potential causes for manuscript, which was critically reviewed and revised by MSB, AH, CG, EB, ML, the difference in VRE prevalence between these neighbor - AV, and AWF. All authors approved the final version. ing countries. Given the increasing prevalence of VRE in Funding Europe, we demonstrate that VRE remains a serious prob- This project is funded by the Ministry of Science and Culture of Lower Saxony lem in healthcare and call for further research to under- (MWK) as part of the Niedersachsen ‘Vorab’ Program. (Grant Agreement No. ZN3831). stand the underlying factors driving the difference in VRE prevalence between countries to develop effective strate - Availability of data and materials gies to control the spread of VRE. Not applicable. Declarations Abbreviations AMR Antimicrobial resistance Ethics approval and consent to participate BSI Blood-stream infection Not applicable. ARMIN Antimicrobial Resistance Monitoring in Lower Saxony ARS National Antimicrobial Resistance Surveillance Consent for Publication CHARE-GD Comparison of healthcare structures, processes and outcomes in Not applicable. the Northern German and Dutch cross-border region EARS-Net E uropean Antimicrobial Resistance Surveillance Network Competing interests ESAC-Net E uropean Surveillance of Antimicrobial Consumption Network The authors declare that they have no competing interests. HCP Healthcare professional ICU Intensive care unit Author details IPC Infection prevention and control Institute for Medical Microbiology and Virology, University of Oldenburg, ISIS-AR I nfectious Diseases Surveillance Information System for Antimicro- Oldenburg, Germany. Department of Medical Microbiology and Infection bial Resistance Prevention, University of Groningen, University Medical Center Groningen, MDRO Multidrug-resistant microorganism Groningen, The Netherlands. Department of Medical Epidemiology, Certe NICU Neonatal intensive care unit Medical Diagnostics and Advice Foundation, Groningen, The Netherlands. KISS Krankenhaus-Infektions-Surveillance-System (Hospital Infection University Hospital Muenster, University of Muenster, Muenster, Germany. Surveillance System from Germany) KRINKO Kommission für Krankenhaushygiene und Infektionsprävention Received: 12 May 2023 Accepted: 19 July 2023 (Commission for Hospital Hygiene and Infection Prevention in Germany) PICU Pediatric intensive care unit RIVM Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment in the Netherlands) References RKI Robert Koch Institute 1. Cattoir V. The multifaceted lifestyle of enterococci: genetic diversity, SARI Antibiotic use and Resistance in ICUs ecology and risks for public health. Curr Opin Microbiol. 2021;65:73–80. SSI Surgical site infection https:// doi. org/ 10. 1016/j. mib. 2021. 10. 013. SO-ZI/AMR Sig naleringsoverleg Zorginstellingen en Antimicrobiële Resisten- 2. Gilmore MS, Lebreton F, van Schaik W. Genomic transition of tie ( The Early Warning and Intervention Meeting for Nosocomial enterococci from gut commensals to leading causes of multidrug- Infections and Antimicrobial Resistance in the Netherlands) resistant hospital infection in the antibiotic era. Curr Opin Microbiol. UTI Urinary tract infection 2013;16(1):10–6. https:// doi. org/ 10. 1016/j. mib. 2013. 01. 006. VRE Vancomycin-resistant enterococci 3. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in VREfm Vancomycin-resistant E. faecium enterococcus. Virulence. 2012;3(5):421–33. https:// doi. org/ 10. 4161/ viru. VSE Vancomycin-susceptible enterococci WIP Werkgroep Infectie Preventie (Infection Prevention Working Group 4. Faron ML, Ledeboer NA, Buchan BW. Resistance mechanisms, epidemi- in the Netherlands) ology, and approaches to screening for vancomycin-resistant entero- WHO World Health Organization coccus in the health care setting. J Clin Microbiol. 2016;54(10):2436–47. https:// doi. org/ 10. 1128/ jcm. 00211- 16. 5. Werner G, Coque TM, Hammerum AM, Hope R, Hryniewicz W, Johnson Supplementary Information A, et al. Emergence and spread of vancomycin resistance among ente- The online version contains supplementary material available at https:// doi. rococci in Europe. Euro Surveill. 2008;13(47):52. org/ 10. 1186/ s13756- 023- 01278-0. 6. Uttley AH, Collins CH, Naidoo J, George RC. Vancomycin-resistant enterococci. Lancet. 1988;1(8575–6):57–8. https:// doi. org/ 10. 1016/ Additional file 1. The final applied search term. s0140- 6736(88) 91037-9. 7. Leclercq R, Derlot E, Duval J, Courvalin P. Plasmid-mediated resistance Additional file 2. Dataset presenting the extracted data. to vancomycin and teicoplanin in Enterococcus faecium. N Engl J Med. 1988;319(3):157–61. https:// doi. org/ 10. 1056/ nejm1 98807 21319 0307. C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 17 of 20 8. Arthur M, Courvalin P. Genetics and mechanisms of glycopeptide resist- 26. Müller J, Voss A, Köck R, Sinha B, Rossen JW, Kaase M, et al. Cross-border ance in enterococci. Antimicrob Agents Chemother. 1993;37(8):1563– comparison of the Dutch and German guidelines on multidrug-resist- 71. https:// doi. org/ 10. 1128/ aac. 37.8. 1563. ant Gram-negative microorganisms. Antimicrob Resist Infect Control. 9. García-Solache M, Rice LB. The Enterococcus: a model of adaptability to 2015;4:7. https:// doi. org/ 10. 1186/ s13756- 015- 0047-6. its environment. Clin Microbiol Rev. 2019;32(2):522. https:// doi. org/ 10. 27. Dik JW, Sinha B, Friedrich AW, Lo-Ten-Foe JR, Hendrix R, Köck R, et al. 1128/ cmr. 00058- 18. Cross-border comparison of antibiotic prescriptions among children 10. Bender JK, Cattoir V, Hegstad K, Sadowy E, Coque TM, Westh H, et al. and adolescents between the north of the Netherlands and the north- Update on prevalence and mechanisms of resistance to linezolid, tige- west of Germany. Antimicrob Resist Infect Control. 2016;5:14. https:// cycline and daptomycin in enterococci in Europe: towards a common doi. org/ 10. 1186/ s13756- 016- 0113-8. nomenclature. Drug Resist Updat. 2018;40:25–39. https:// doi. org/ 10. 28. Köck R, Becker K, Idelevich EA, Jurke A, Glasner C, Hendrix R, et al. Pre- 1016/j. drup. 2018. 10. 002. vention and control of multidrug-resistant bacteria in The Netherlands 11. Klare I, Fleige C, Geringer U, Thürmer A, Bender J, Mutters NT, et al. and Germany-the impact of healthcare structures. Int J Environ Res Increased frequency of linezolid resistance among clinical Enterococ- Public Health. 2020;17(7):522. https:// doi. org/ 10. 3390/ ijerp h1707 2337. cus faecium isolates from German hospital patients. J Glob Antimicrob 29. Keizer J, Braakman-Jansen LMA, Kampmeier S, Köck R, Al Naiemi N, Te Resist. 2015;3(2):128–31. https:// doi. org/ 10. 1016/j. jgar. 2015. 02. 007. Riet-Warning R, et al. Cross-border comparison of antimicrobial resist- 12. Schulte B, Heininger A, Autenrieth IB, Wolz C. Emergence of increas- ance (AMR) and AMR prevention measures: the healthcare workers’ ing linezolid-resistance in enterococci in a post-outbreak situation perspective. Antimicrob Resist Infect Control. 2019;8:123. https:// doi. with vancomycin-resistant Enterococcus faecium. Epidemiol Infect. org/ 10. 1186/ s13756- 019- 0577-4. 2008;136(8):1131–3. https:// doi. org/ 10. 1017/ s0950 26880 70095 08. 30. Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. 13. Krull M, Klare I, Ross B, Trenschel R, Beelen DW, Todt D, et al. Emergence PRISMA extension for scoping reviews (PRISMA-ScR): checklist and of linezolid- and vancomycin-resistant Enterococcus faecium in a depart- explanation. Ann Intern Med. 2018;169(7):467–73. https:// doi. org/ 10. ment for hematologic stem cell transplantation. Antimicrob Resist 7326/ m18- 0850. Infect Control. 2016;5:31. https:// doi. org/ 10. 1186/ s13756- 016- 0131-6. 31. NethMap: Report about consumption of antimicrobial agents and 14. Werner G, Gfrörer S, Fleige C, Witte W, Klare I. Tigecycline-resistant antimicrobial resistance among medically important bacteria in the Enterococcus faecalis strain isolated from a German intensive care unit Netherlands. patient. J Antimicrob Chemother. 2008;61(5):1182–3. https:// doi. org/ 10. 32. Epidemiologisches Bulletin. Aktuelle Daten und Informationen zu 1093/ jac/ dkn065. Infektionskrankheiten und Public Health. Robert Koch Institute. 15. Monteserin N, Larson E. Temporal trends and risk factors for healthcare- 33. ARS. Antibiotika-Resistenz-Surveillance in Deutschland. Available from: associated vancomycin-resistant enterococci in adults. J Hosp Infect. https:// ars. rki. de/. 2016;94(3):236–41. https:// doi. org/ 10. 1016/j. jhin. 2016. 07. 023. 34. Timmers GJ, van der Zwet WC, Simoons-Smit IM, Savelkoul PH, Meester 16. Top J, Willems R, Bonten M. Emergence of CC17 Enterococcus faecium: HH, Vandenbroucke-Grauls CM, et al. Outbreak of vancomycin-resistant from commensal to hospital-adapted pathogen. FEMS Immunol Med Enterococcus faecium in a haematology unit: risk factor assessment and Microbiol. 2008;52(3):297–308. https:// doi. org/ 10. 1111/j. 1574- 695X. successful control of the epidemic. Br J Haematol. 2002;116(4):826–33. 2008. 00383.x.https:// doi. org/ 10. 1046/j. 0007- 1048. 2002. 03339.x. 17. Ford CD, Gazdik MA, Lopansri BK, Webb B, Mitchell B, Coombs J, et al. 35. van der Steen LF, Bonten MJ, van Kregten E, Harssema-Poot JJ, Willems Vancomycin-resistant enterococcus colonization and bacteremia and R, Gaillard CA. Vancomycin-resistant Enterococcus faecium outbreak in a hematopoietic stem cell transplantation outcomes. Biol Blood Marrow nephrology ward. Ned Tijdschr Geneeskd. 2000;144(53):2568–72. Transpl. 2017;23(2):340–6. https:// doi. org/ 10. 1016/j. bbmt. 2016. 11. 017. 36. Mascini EM, Troelstra A, Beitsma M, Blok HE, Jalink KP, Hopmans TE, et al. 18. Bonten MJ, Willems R, Weinstein RA. Vancomycin-resistant enterococci: Genotyping and preemptive isolation to control an outbreak of vanco- why are they here, and where do they come from? Lancet Infect Dis. mycin-resistant Enterococcus faecium. Clin Infect Dis. 2006;42(6):739–46. 2001;1(5):314–25. https:// doi. org/ 10. 1016/ s1473- 3099(01) 00145-1. 37. Frakking FNJ, Bril WS, Sinnige JC, Klooster JEV, de Jong BAW, van Han- 19. DiazGranados CA, Zimmer SM, Klein M, Jernigan JA. Comparison of nen EJ, et al. Recommendations for the successful control of a large mortality associated with vancomycin-resistant and vancomycin- outbreak of vancomycin-resistant Enterococcus faecium in a non- susceptible enterococcal bloodstream infections: a meta-analysis. Clin endemic hospital setting. J Hosp Infect. 2018;100(4):e216–25. https:// Infect Dis. 2005;41(3):327–33.doi. org/ 10. 1016/j. jhin. 2018. 02. 016. 20. Kramer TS, Remschmidt C, Werner S, Behnke M, Schwab F, Werner 38. Weterings V, van Oosten A, Nieuwkoop E, Nelson J, Voss A, Winter- G, et al. The importance of adjusting for enterococcus species when mans B, et al. Management of a hospital-wide vancomycin-resistant assessing the burden of vancomycin resistance: a cohort study Enterococcus faecium outbreak in a Dutch general hospital, 2014–2017: including over 1000 cases of enterococcal bloodstream infections. successful control using a restrictive screening strategy. Antimi- Antimicrob Resist Infect Control. 2018;7:133. https:// doi. org/ 10. 1186/ crob Resist Infect Control. 2021;10(1):38. https:// doi. org/ 10. 1186/ s13756- 018- 0419-9.s13756- 021- 00906-x. 21. Salgado CD, Farr BM. Outcomes associated with vancomycin- 39. Zhou X, Chlebowicz MA, Bathoorn E, Rosema S, Couto N, Lokate M, resistant enterococci: a meta-analysis. Infect Control Hosp Epidemiol. et al. Elucidating vancomycin-resistant Enterococcus faecium outbreaks: 2003;24(9):690–8. the role of clonal spread and movement of mobile genetic elements. J 22. Carmeli Y, Eliopoulos G, Mozaffari E, Samore M. Health and economic Antimicrob Chemother. 2018;73(12):3259–67. https:// doi. org/ 10. 1093/ outcomes of vancomycin-resistant enterococci. Arch Intern Med. jac/ dky349. 2002;162(19):2223–8. 40. Lisotto P, Couto N, Rosema S, Lokate M, Zhou X, Bathoorn E, et al. 23. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet Molecular characterisation of vancomycin-resistant Enterococcus DL, et al. Discovery, research, and development of new antibiotics: the faecium isolates belonging to the lineage ST117/CT24 causing hospital WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet outbreaks. Front Microbiol. 2021;12(2741):52. https:// doi. org/ 10. 3389/ Infect Dis. 2018;18(3):318–27. https:// doi. org/ 10. 1016/ s1473- 3099(17) fmicb. 2021. 728356. 30753-3. 41. Gast KB, van Oudheusden AJG, Murk JL, Stohr J, Buiting AG, Verweij JJ. 24. European Centre for Disease Prevention and Control. Antimicrobial Successful containment of two vancomycin-resistant Enterococcus fae- resistance in the EU/EEA (EARS-Net)-Annual Epidemiological Report cium ( VRE) outbreaks in a Dutch teaching hospital using environmental 2019. Stockholm: ECDC; 2020 sampling and whole-genome sequencing. J Hosp Infect. 2021;5:63. 25. Gunnink LB, Arouri DJ, Jolink FEJ, Lokate M, de Jonge K, Kampmeier https:// doi. org/ 10. 1016/j. jhin. 2021. 02. 007. S, et al. Compliance to screening protocols for multidrug-resistant 42. Elsner HA, Sobottka I, Feucht HH, Harps E, Haun C, Mack D, et al. microorganisms at the emergency departments of two academic Nosocomial outbreak of vancomycin-resistant Enterococcus faecium hospitals in the Dutch-German cross-border region. Trop Med Infect at a German university pediatric hospital. Int J Hyg Environ Health. Dis. 2021;6(1):522. https:// doi. org/ 10. 3390/ tropi calme d6010 015. 2000;203(2):147–52. https:// doi. org/ 10. 1078/ s1438- 4639(04) 70020-6. Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 18 of 20 43. Knoll M, Daeschlein G, Okpara-Hofmann J, Klare I, Wilhelms D, Wolf HH, Enterococcus faecium from hospital admission screening in an endemic et al. Outbreak of vancomycin-resistant enterococci ( VRE) in a hemato- region in Germany. J Glob Antimicrob Resist. 2020;22:646–50. https:// logical oncology ward and hygienic preventive measures A long-term doi. org/ 10. 1016/j. jgar. 2020. 05. 003. study. Onkologie. 2005;28(4):187–92. https:// doi. org/ 10. 1159/ 00008 59. Chhatwal P, Ebadi E, Thol F, Koenecke C, Beutel G, Ziesing S, et al. 4061. Prospective infection surveillance and systematic screening for 44. Borgmann S, Niklas DM, Klare I, Zabel LT, Buchenau P, Autenrieth IB, vancomycin-resistant enterococci in hematologic and oncologic et al. Two episodes of vancomycin-resistant Enterococcus faecium patients-findings of a German tertiary care center. J Glob Antimicrob outbreaks caused by two genetically different clones in a newborn Resist. 2020;22:102–5. https:// doi. org/ 10. 1016/j. jgar. 2020. 02. 012. intensive care unit. Int J Hyg Environ Health. 2004;207(4):386–9. https:// 60. Trautmannsberger I, Kolberg L, Meyer-Buehn M, Huebner J, Werner G, doi. org/ 10. 1078/ 1438- 4639- 00304. Weber R, et al. Epidemiological and genetic characteristics of vanco- 45. Borgmann S, Schulte B, Wolz C, Gruber H, Werner G, Goerke C, et al. mycin-resistant Enterococcus faecium isolates in a University Children’s Discrimination between epidemic and non-epidemic glycopeptide- Hospital in Germany: 2019 to 2020. Antimicrob Resist Infect Control. resistant E. faecium in a post-outbreak situation. J Hosp Infect. 2022;11(1):48. https:// doi. org/ 10. 1186/ s13756- 022- 01081-3. 2007;67(1):49–55. https:// doi. org/ 10. 1016/j. jhin. 2007. 06. 002. 61. Messler S, Klare I, Wappler F, Werner G, Ligges U, Sakka SG, et al. 46. Liese J, Schüle L, Oberhettinger P, Tschörner L, Nguyen T, Dörfel D, Reduction of nosocomial bloodstream infections and nosocomial et al. Expansion of vancomycin-resistant Enterococcus faecium in an vancomycin-resistant Enterococcus faecium on an intensive care unit academic tertiary hospital in Southwest Germany: a large-scale whole- after introduction of antiseptic octenidine-based bathing. J Hosp Infect. genome-based outbreak investigation. Antimicrob Agents Chemother. 2019;101(3):264–71. https:// doi. org/ 10. 1016/j. jhin. 2018. 10. 023. 2019. https:// doi. org/ 10. 1128/ aac. 01978- 18. 62. Biehl LM, Higgins PG, Stemler J, Gilles M, Peter S, Dörfel D, et al. Impact 47. Bender JK, Hermes J, Zabel LT, Haller S, Mürter N, Blank HP, et al. Control- of single-room contact precautions on acquisition and transmission of ling an unprecedented outbreak with vancomycin-resistant Enterococ- vancomycin-resistant enterococci on haematological and oncological cus faecium in Germany, October 2015 to November 2019. Microorgan- wards, multicentre cohort-study, Germany, January-December 2016. isms. 2022;10(8):258. https:// doi. org/ 10. 3390/ micro organ isms1 00816 03. Euro Surveill. 2022;27(2):522. https:// doi. org/ 10. 2807/ 1560- 7917. Es. 48. Nys S, Bruinsma N, Filius PM, van den Bogaard AE, Hoffman L, Terporten 2022. 27.2. 20018 76. PH, et al. Eec ff t of hospitalization on the antibiotic resistance of fecal 63. Zhou X, García-Cobos S, Ruijs G, Kampinga GA, Arends JP, Borst DM, Enterococcus faecalis of surgical patients over time. Microb Drug Resist. et al. Epidemiology of extended-spectrum β-lactamase-producing E. 2005;11(2):154–8. https:// doi. org/ 10. 1089/ mdr. 2005. 11. 154. coli and vancomycin-resistant Enterococci in the northern Dutch- 49. Guiot HF, Peetermans WE, Sebens FW. Isolation of vancomycin-resistant German cross-border region. Front Microbiol. 2017;8:1914. https:// doi. enterococci in haematologic patients. Eur J Clin Microbiol Infect Dis. org/ 10. 3389/ fmicb. 2017. 01914. 1991;10(1):32–4. https:// doi. org/ 10. 1007/ bf019 67094. 64. Glasner C, Berends MS, Becker K, Esser J, Gieffers J, Jurke A, et al. A pro - 50. van den Braak N, Ott A, van Belkum A, Kluytmans JA, Koeleman JG, spective multicentre screening study on multidrug-resistant organisms Spanjaard L, et al. Prevalence and determinants of fecal colonization in intensive care units in the Dutch-German cross-border region, 2017 with vancomycin-resistant Enterococcus in hospitalized patients in The to 2018: the importance of healthcare structures. Euro Surveill. 2022. Netherlands. Infect Control Hosp Epidemiol. 2000;21(8):520–4. https:// https:// doi. org/ 10. 2807/ 1560- 7917. Es. 2022. 27.5. 20016 60. doi. org/ 10. 1086/ 501797. 65. Remschmidt C, Schröder C, Behnke M, Gastmeier P, Geffers C, Kramer 51. Wendt C, Krause C, Xander LU, Löffler D, Floss H. Prevalence of coloniza- TS. Continuous increase of vancomycin resistance in enterococci tion with vancomycin-resistant enterococci in various population causing nosocomial infections in Germany- 10 years of surveillance. groups in Berlin, Germany. J Hosp Infect. 1999;42(3):193–200. https:// Antimicrob Resist Infect Control. 2018;7:54. https:// doi. org/ 10. 1186/ doi. org/ 10. 1053/ jhin. 1999. 0597.s13756- 018- 0353-x. 52. Gruber I, Heudorf U, Werner G, Pfeifer Y, Imirzalioglu C, Ackermann H, 66. Correa-Martínez CL, Jurke A, Schmitz J, Schaumburg F, Kampmeier et al. Multidrug-resistant bacteria in geriatric clinics, nursing homes, S, Mellmann A. Molecular epidemiology of vancomycin-resistant and ambulant care–prevalence and risk factors. Int J Med Microbiol. Enterococci bloodstream infections in germany: a population-based 2013;303(8):405–9. https:// doi. org/ 10. 1016/j. ijmm. 2013. 05. 002. prospective longitudinal study. Microorganisms. 2022. https:// doi. org/ 53. Liss BJ, Vehreschild JJ, Cornely OA, Hallek M, Fätkenheuer G, Wispling-10. 3390/ micro organ isms1 00101 30. hoff H, et al. Intestinal colonisation and blood stream infections due to 67. Gastmeier P, Schröder C, Behnke M, Meyer E, Geffers C. Dramatic vancomycin-resistant enterococci ( VRE) and extended-spectrum beta- increase in vancomycin-resistant enterococci in Germany. J Antimicrob lactamase-producing Enterobacteriaceae (ESBLE) in patients with hae- Chemother. 2014;69(6):1660–4. https:// doi. org/ 10. 1093/ jac/ dku035. matological and oncological malignancies. Infection. 2012;40(6):613–9. 68. Brinkwirth S, Martins S, Ayobami O, Feig M, Noll I, Zacher B, et al. Germa- https:// doi. org/ 10. 1007/ s15010- 012- 0269-y. ny’s burden of disease of bloodstream infections due to vancomycin- 54. Neumann B, Bender JK, Maier BF, Wittig A, Fuchs S, Brockmann D, et al. resistant Enterococcus faecium between 2015–2020. Microorganisms. Comprehensive integrated NGS-based surveillance and contact-net- 2022. https:// doi. org/ 10. 3390/ micro organ isms1 01122 73. work modeling unravels transmission dynamics of vancomycin-resist- 69. Aardema H, Arends JP, de Smet AM, Zijlstra JG. Burden of highly ant enterococci in a high-risk population within a tertiary care hospital. resistant microorganisms in a Dutch intensive care unit. Neth J Med. PLoS One. 2020;15(6):e0235160. 2015;73(4):169–74. 55. Bui MT, Rohde AM, Schwab F, Märtin N, Kipnis M, Boldt AC, et al. 70. Jones ME, Draghi DC, Thornsberry C, Karlowsky JA, Sahm DF, Wenzel RP. Prevalence and risk factors of colonisation with vancomycin-resistant Emerging resistance among bacterial pathogens in the intensive care Enterococci faecium upon admission to Germany’s largest university unit-a European and North American Surveillance study (2000–2002). hospital. GMS Hyg Infect Control. 2021;16:52. https:// doi. org/ 10. 3205/ Ann Clin Microbiol Antimicrob. 2004;3:14. https:// doi. org/ 10. 1186/ dgkh0 00377.1476- 0711-3- 14. 56. Xanthopoulou K, Peter S, Tobys D, Behnke M, Dinkelacker AG, Eisenbeis 71. Kohlenberg A, Schwab F, Meyer E, Behnke M, Geffers C, Gastmeier P. S, et al. Vancomycin-resistant Enterococcus faecium colonizing patients Regional trends in multidrug-resistant infections in German intensive on hospital admission in Germany: prevalence and molecular epidemi- care units: a real-time model for epidemiological monitoring and analy- ology. J Antimicrob Chemother. 2020;75(10):2743–51. https:// doi. org/ sis. J Hosp Infect. 2009;73(3):239–45. https:// doi. org/ 10. 1016/j. jhin. 2009. 10. 1093/ jac/ dkaa2 71.07. 017. 57. Sommer L, Hackel T, Hofmann A, Hoffmann J, Hennebach E, Köpke 72. Remschmidt C, Behnke M, Kola A, Peña Diaz LA, Rohde AM, Gastmeier B, et al. Multi-resistant bacteria in patients in hospitals and medical P, et al. The effect of antibiotic use on prevalence of nosocomial practices as well as in residents of nursing homes in saxony-results of a vancomycin-resistant enterococci- an ecologic study. Antimicrob Resist prevalence study 2017/2018. Gesundheitswesen. 2020. https:// doi. org/ Infect Control. 2017;6:95. https:// doi. org/ 10. 1186/ s13756- 017- 0253-5. 10. 1055/a- 1138- 0489. 73. Hübner NO, Wegner C, Gleich S. Multidrug-resistant organisms 58. Heininger A, Zimmermann S, Bootsveld C, Boutin S, Nurjadi D. and C. difficile in Munich acute-care clinics: results from a point Low prevalence of combined linezolid- and vancomycin-resistant prevalence study of clinical routine data. Bundesgesundheitsblatt C imen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 19 of 20 Gesundheitsforschung Gesundheitsschutz. 2015;58(11–12):1306–13. 93. Werner G, Coque TM, Franz CM, Grohmann E, Hegstad K, Jensen L, https:// doi. org/ 10. 1007/ s00103- 015- 2248-9. et al. Antibiotic resistant enterococci-tales of a drug resistance gene 74. Meyer E, Ziegler R, Mattner F, Schwab F, Gastmeier P, Martin M. Increase trafficker. Int J Med Microbiol. 2013;303(6–7):360–79. https:// doi. org/ 10. of patients co-colonised or co-infected with methicillin-resistant 1016/j. ijmm. 2013. 03. 001. Staphylococcus aureus, vancomycin-resistant Enterococcus faecium or 94. Boeing C, Correa-Martinez CL, Schuler F, Mellmann A, Karch A, extended-spectrum β-lactamase-producing Enterobacteriaceae. Infec- Kampmeier S. Development and validation of a tool for the predic- tion. 2011;39(6):501–6. https:// doi. org/ 10. 1007/ s15010- 011- 0154-0. tion of vancomycin-resistant Enterococci colonization persistence-the 75. Remschmidt C, Schneider S, Meyer E, Schroeren-Boersch B, Gastmeier P, PREVENT score. Microbiol Spectr. 2021;9(2):e0035621. https:// doi. org/ Schwab F. Surveillance of antibiotic use and resistance in intensive care 10. 1128/ Spect rum. 00356- 21. units (SARI). Dtsch Arztebl Int. 2017;114(50):858–65. https:// doi. org/ 10. 95. Weinstock DM, Conlon M, Iovino C, Aubrey T, Gudiol C, Riedel E, et al. 3238/ arzte bl. 2017. 0858. Colonization, bloodstream infection, and mortality caused by vancomy- 76. Kramer A, Ryll S, Wegner C, Jatzwauk L, Popp W, Hübner NO. One-day cin-resistant enterococcus early after allogeneic hematopoietic stem point prevalence of emerging bacterial pathogens in four secondary cell transplant. Biol Blood Marrow Transplant. 2007;13(5):615–21. and five tertiary care German hospitals - results from a pilot study of the https:// doi. org/ 10. 1016/j. bbmt. 2007. 01. 078. German Society for Hospital Hygiene (Deutsche Gesellschaft für Krank- 96. Alevizakos M, Gaitanidis A, Nasioudis D, Tori K, Flokas ME, Mylonakis E. enhaushygiene, DGKH). GMS Krankenhhyg Interdiszip. 2011. https:// doi. Colonization with vancomycin-resistant enterococci and risk for blood- org/ 10. 3205/ dgkh0 00177. stream infection among patients with malignancy: a systematic review 77. Wegner C, Hübner NO, Gleich S, Thalmaier U, Krüger CM, Kramer and meta-analysis. Open Forum Infect Dis. 2017;4(1):ofw246. A. One-day point prevalence of emerging bacterial pathogens in a 97. Zhou X, Willems RJL, Friedrich AW, Rossen JWA, Bathoorn E. Enterococ- nationwide sample of 62 German hospitals in 2012 and comparison cus faecium: from microbiological insights to practical recommenda- with the results of the one-day point prevalence of 2010. GMS Hyg tions for infection control and diagnostics. Antimicrob Resist Infect Infect Control. 2013. https:// doi. org/ 10. 3205/ dgkh0 00212. Control. 2020;9(1):130. https:// doi. org/ 10. 1186/ s13756- 020- 00770-1. 78. Huebner NO, Dittmann K, Henck V, Wegner C, Kramer A. Epidemiology 98. Werkgroep Infectiepreventie. WIP-Richtlijn BRMO (Bijzonder Resistente of multidrug resistant bacterial organisms and Clostridium difficile in Micro-Organismen) [ZKH]; RIVM: Bilthoven, The Nether- lands, 2013. German hospitals in 2014: results from a nationwide one-day point 99. Jackson SS, Harris AD, Magder LS, Stafford KA, Johnson JK, Miller LG, prevalence of 329 German hospitals. BMC Infect Dis. 2016;16(1):467. et al. Bacterial burden is associated with increased transmission to https:// doi. org/ 10. 1186/ s12879- 016- 1756-z. health care workers from patients colonized with vancomycin-resistant 79. Scharlach M, Wagner D, Dreesman J, Pulz M. Antimicrobial resistance Enterococcus. Am J Infect Control. 2019;47(1):13–7. https:// doi. org/ 10. monitoring in Lower Saxony (ARMIN): first trends for MRSA, ESBL-pro -1016/j. ajic. 2018. 07. 011. ducing Escherichia coli and VRE from 2006 to 2010. Gesundheitswesen. 100. Empfehlung der Kommission für Krankenhaushygiene und Infektionspr 2011;73(11):744–7. https:// doi. org/ 10. 1055/s- 0031- 12912 65. ̈avention (KRINKO) beim Robert Koch Institut. Hygienemaßnahmen zur 80. Infectious Diseases Surveillance Information System for Antimicrobial Prävention der Infektion durch Enterokokken mit speziellen Antibioti- Resistance (ISIS-AR) [October, 2021]. Available from: https:// www. rivm. karesistenzen. Bundesgesundheitsblatt Gesundheitsforschung Gesund- nl/ isis- ar. heitsschutz. (61):1310–61. https:// doi. org/ 10. 1007/ s00103- 018- 2811-2. 81. The Dutch Working Party on Antibiotic Policy (SWAB) [October, 2021]. 101. Samenwerkingsverband Richtlijnen Infectiepreventie (SRI) [May, Available from: https:// swab. nl/ en/ nethm ap- pvid3 69. 2022]. Available from: https:// www. sri- richt lijnen. nl/ nieuws/ 82. Signaleringsoverleg ziekenhuisinfecties en antimicrobiële resistentie kom- naar- kick- off- van- sri. (SO-ZI/AMR) [October, 2021]. Available from: https:// www. rivm. nl/ surve 102. Austin DJ, Bonten MJ, Weinstein RA, Slaughter S, Anderson RM. illan ce- van- infec tiezi ekten/ signa lering- infec tiezi ekten/ signa lerin gsove Vancomycin-resistant enterococci in intensive-care hospital settings: rleg- zi- amr. transmission dynamics, persistence, and the impact of infection control 83. Zum Auftreten und zur Verbreitung glycopeptidresistenter Enterokok- programs. Proc Natl Acad Sci U S A. 1999;96(12):6908–13. https:// doi. ken-Update 2003/2004. Epidemiologisches Bull. 2005(17): 149–155.org/ 10. 1073/ pnas. 96. 12. 6908. 84. Vancomycin-resistente Enterokokken in deutschen Krankenhäusern 103. McKinnell JA, Kunz DF, Chamot E, Patel M, Shirley RM, Moser SA, et al. 2006/2007. Epidemiologisches Bull. 2008(23): 179–188. Association between vancomycin-resistant Enterococci bacteremia and 85. ARS (Antibiotika-Resistenz-Surveillance in Deutschland), Datenbank: ceftriaxone usage. Infect Control Hosp Epidemiol. 2012;33(7):718–24. Resistenzübersicht E. faecium, E. faecalis; Blutkulturen bzw. ambulanter 104. Harbarth S, Cosgrove S, Carmeli Y. Eec ff ts of antibiotics on nosocomial Bereich, 2000–2020 (https:// ars. rki. de/). epidemiology of vancomycin-resistant enterococci. Antimicrob Agents 86. Nationales Referenzzentrum (NRZ) für Staphylokokken und Enterokok- Chemother. 2002;46(6):1619–28. https:// doi. org/ 10. 1128/ aac. 46.6. 1619- ken. Available from: https:// www. rki. de/ DE/ Conte nt/ Infekt/ NRZ/ Staph 1628. 2002. yloko kken/ staph ylo_ node. html; jsess ionid= 81576 F122A 8322F A38F6 105. Fridkin SK, Edwards JR, Courval JM, Hill H, Tenover FC, Lawton R, et al. 904EF EE588 CE. inter net062. The effect of vancomycin and third-generation cephalosporins on 87. Klare I, Bender JK, Werner G, Marktwart R, Reuss A, Sin MA, et al. prevalence of vancomycin-resistant enterococci in 126 U.S. adult inten- Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten sive care units. Ann Intern Med. 2001;135(3):175–83. https:// doi. org/ 10. Enterokokken in Deutschland. Epidemiologisches Bull. 2019;35:365–72.7326/ 0003- 4819- 135-3- 20010 8070- 00009. 88. Weber RE, Bender JK, Werner G, Noll I, Abu Sin M, Eckmanns T. Eigen- 106. Kritsotakis EI, Christidou A, Roumbelaki M, Tselentis Y, Gikas A. The schaften, Häufigkeit und Verbreitung von Vancomycin-resistenten dynamic relationship between antibiotic use and the incidence of Enterokokken ( VRE) in Deutschland-update 2019/2020. Epidemiologis- vancomycin-resistant Enterococcus: time-series modelling of 7-year ches Bulletin. 2021;27:32–42. surveillance data in a tertiary-care hospital. Clin Microbiol Infect. 89. European Centre for Disease Prevention and Control. Antimicrobial 2008;14(8):747–54. https:// doi. org/ 10. 1111/j. 1469- 0691. 2008. 02026.x. resistance in the EU/EEA (EARS-Net) - Annual Epidemiological Report 107. ECDC. European Surveillance of Antimicrobial Consumption Network 2021. Stockholm: ECDC; 2022. (ESAC- Net) - Distribution of antimicrobial consumption by antimicro- 90. European Centre for Disease Prevention and Control, Annual surveil- bial group. Available from: https:// www. ecdc. europa. eu/ en/ antim icrob lance reports on antimicrobial resistance. https:// www. ecdc. europa. eu/ ial- consu mption/ datab ase/ distr ibuti on- by- antim icrob ial- group. en/ antim icrob ial- resis tance/ surve illan ce- and- disea se- data/ report. 108. Boschert AL, Arndt F, Hamprecht A, Wolke M, Walker SV. Comparison of 91. European Centre for Disease Prevention and Control. Surveillance of five different selective agar for the detection of vancomycin-resistant antimicrobial resistance in Europe, 2020 data. Stockholm: 2021. Report Enterococcus faecium. Antibiotics (Basel). 2023;12(4):558. https:// doi. org/ No.10. 3390/ antib iotic s1204 0666. 92. European Centre for Disease Prevention and Control (ECDC). Surveil- 109. Seo JY, Kim PW, Lee JH, Song JH, Peck KR, Chung DR, et al. Evaluation of lance Atlas of Infectious Diseases. [March, 2023]. Available from: https:// PCR-based screening for vancomycin-resistant enterococci compared www. ecdc. europa. eu/ en/ antim icrob ial- resis tance/ surve illan ce- and- with a chromogenic agar-based culture method. J Med Microbiol. disea se- data/ data- ecdc. 2011;60:945–9. https:// doi. org/ 10. 1099/ jmm.0. 029777-0. Cimen et al. Antimicrobial Resistance & Infection Control (2023) 12:78 Page 20 of 20 110. European Centre for Disease Prevention and Control (ECDC). Surveil- lance of antimicrobial resistance in Europe, 2020 data [February, 2022]. Available from: https:// www. ecdc. europa. eu/ en/ publi catio ns- data/ surve illan ce- antim icrob ial- resis tance- europe- 2020. 111. Werner G, Neumann B, Weber RE, Kresken M, Wendt C, Bender JK. Thirty years of VRE in Germany-expect the unexpected: the view from the National Reference Centre for Staphylococci and Enterococci. Drug Resist Updat. 2020;53:100732. https:// doi. org/ 10. 1016/j. drup. 2020. 112. Klare I, Bender JK, Fleige C, Kriebel N, Hamprecht A, Gatermann S, et al. Comparison of VITEK 2, three different gradient strip tests and broth microdilution for detecting vanB-positive Enterococcus faecium isolates with low vancomycin MICs. J Antimicrob Chemother. 2019;74(10):2926–9. 113. Walker SV, Wolke M, Plum G, Weber RE, Werner G, Hamprecht A. Failure of Vitek2 to reliably detect vanB-mediated vancomycin resistance in Enterococcus faecium. J Antimicrob Chemother. 2021;76(7):1698–702. 114. EUCAST. Vancomycin susceptibility testing in Enterococcus faecalis and E. faecium using MIC gradient tests–a modified warning 21 May, 2019. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub- lished maps and institutional affiliations. Re Read ady y to to submit y submit your our re researc search h ? Choose BMC and benefit fr ? Choose BMC and benefit from om: : fast, convenient online submission thorough peer review by experienced researchers in your ﬁeld rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions
Antimicrobial Resistance and Infection Control – Springer Journals
Published: Aug 12, 2023
Keywords: Vancomycin-resistant enterococci; VRE; Antibiotic resistance; Epidemiology; Prevalence; Dutch-German cross-border region; Germany; The Netherlands
Access the full text.
Sign up today, get DeepDyve free for 14 days.