Increasing Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae (ESBL) and the Relation to Consumption of Broad-Spectrum Antimicrobial Agents 2003-2011 in a Large Area of Copenhagen, Denmark


Purpose: To investigate 1) the development in the incidence of ESBL-producing bacteria in hospitals and primary health care, 2) the contribution of primary health care to the incidence of ESBL-producing bacteria, and 3) the development in resistance patterns for all Escherichia coli and Klebsiella pneumoniae isolates in relation to antimicrobial consumption in hospitals and primary health care. Methods: ESBL-data were retrospectively collected from bacterial isolates from all specimens received at the Department of Clinical Microbiology from 2003 to 2011 together with the corresponding patient data. ESBL-production was detected in isolates from 1067 of 59,373 patients (1.8%) with an E. coli infection and in 263 of 8660 patients (3.0%) with a K. pneumoniae infection. Results: From 2003 to 2009, an increase in patients with an ESBL-producing isolate occurred in both hospitals and primary health care at the same time as an increased consumption of broad-spectrum antimicrobial agents was seen. Interventions to reduce prescription of cephalosporins and ciprofloxacin at the hospitals from 2010 resulted in a remarkable decrease in patients with ESBL-producing K. pneumoniae whereas a continuing increase was seen in patients with ESBL-producing E. coli both at hospitals and in primary health care. The proportion of patients with community-acquired ESBL-producing E. coli was stable with an increase of only 1.4% from 2007 to 2011. Conclusions: Reduction in prescription of broad-spectrum antimicrobial agents at the hospital level had an important impact on the incidence of ESBL-producing K. pneumoniae, but not on ESBL-producing E. coli.

Share and Cite:

Nielsen, L. , Kjerulf, A. and Arpi, M. (2015) Increasing Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae (ESBL) and the Relation to Consumption of Broad-Spectrum Antimicrobial Agents 2003-2011 in a Large Area of Copenhagen, Denmark. Open Journal of Medical Microbiology, 5, 28-42. doi: 10.4236/ojmm.2015.51005.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Nordmann, P., Naas, T. and Poirel, L. (2011) Global Spread of Carbapenemase-Producing Enterobacteriaceae. Emerging Infectious Diseases, 17, 1791-1798.
[2] Paterson, D.L. and Bonom,o R.A. (2005) Extended-Spectrum Beta-Lactamases: A Clinical Update. Clinical Microbiology Reviews, 18, 657-686.
[3] Pitout, J.D. and Laupland, K.B. (2008) Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae: An Emerging Public-Health Concern. The Lancet Infectious Diseases, 8, 159-166.
[4] Bradford, P.A. (2001) Extended-Spectrum Beta-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat. Clinical Microbiology Reviews, 14, 933-951.
[5] Bush, K. and Jacoby, G.A. (2010) Updated Functional Classification of Beta-Lactamases. Antimicrobial Agents and Chemotherapy, 54, 969-976.
[6] Canton, R. and Coque, T.M. (2006) The CTX-M Beta-Lactamase Pandemic. Current Opinion in Microbiology, 9, 466-475.
[7] Oteo, J., Perez-Vazquez, M. and Campos, J. (2010) Extended-Spectrum [Beta]-Lactamase Producing Escherichia coli: Changing Epidemiology and Clinical Impact. Current Opinion in Infectious Diseases, 23, 320-326.
[8] Lytsy, B., Sandegren, L., Tano, E., Torell, E., Andersson, D.I. and Melhus, A. (2008) The First Major Extended-Spectrum Beta-Lactamase Outbreak in Scandinavia Was Caused by Clonal Spread of a Multiresistant Klebsiella pneumoniae Producing CTX-M-15. APMIS: Acta Pathologica, Microbiologica, et immunologica Scandinavica, 116, 302-308.
[9] ESBL in Sweden.
[10] DANMAP (2011) Use of Antimicrobial Agents and Occurrence of Antimicrobial Resistance in Bacteria from Food Animals, Food and Humans in Denmark 2011.
[11] Hansen, D.S., Schumacher, H., Hansen, F., Stegger, M., Hertz, F.B., Schonning, K., et al. (2012) Extended-Spectrum Beta-Lactamase (ESBL) in Danish Clinical Isolates of Escherichia coli and Klebsiella pneumoniae: Prevalence, Beta-Lactamase Distribution, Phylogroups, and Co-Resistance. Scandinavian Journal of Infectious Diseases, 44, 174-181.
[12] NORM/NORM-VET (2011) Consumption of Antimicrobial Agents and Occurrence of Antimicrobial Resistance in Norway.
[13] Annual Epidemiological Report on Communicable Diseases in Europe 2011.
[14] (SRGA). TSRGfA.
[15] EUCAST (2013) TECoAST.
[16] Group M. ESBL and AmpC Detection Disc Sets.
[17] Hansen, D.S., Sirot, D. and Kolmos, H.J. (1998) Extended Spectrum Beta-Lactamases in Danish Klebsiella Isolates. Ugeskrift for Laeger, 160, 2261-2262.
[18] Kjerulf, A., Hansen, D.S., Sandvang, D., Hansen, F. and Frimodt-Moller, N. (2008) The Prevalence of ESBL-Producing E. coli and Klebsiella Strains in the Copenhagen Area of Denmark. APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica, 116, 118-124.
[19] Andersen, S.E. and Knudsen, J.D. (2013) A Managed Multidisciplinary Programme on Multi-Resistant Klebsiella pneumoniae in a Danish University Hospital. BMJ Quality & Safety, 22, 907-915.
[20] Aldeyab, M.A., Harbarth, S., Vernaz, N., Kearney, M.P., Scott, M.G., Darwish Elhajji, F.W., et al. (2012) The Impact of Antibiotic Use on the Incidence and Resistance Pattern of Extended-Spectrum Beta-Lactamase-Producing Bacteria in Primary and Secondary Healthcare Settings. British Journal of Clinical Pharmacology, 74, 171-179.
[21] Deege, M.P. and Paterson, D.L. (2011) Reducing the Development of Antibiotic Resistance in Critical Care Units. Current Pharmaceutical Biotechnology, 12, 2062-2069.
[22] Hanberger, H., Arman, D., Gill, H., Jindrak, V., Kalenic, S., Kurcz, A., et al. (2009) Surveillance of Microbial Resistance in European Intensive Care Units: A First Report from the Care-ICU Programme for Improved Infection Control. Intensive Care Medicine, 35, 91-100.
[23] Owens Jr., R.C. and Rice, L. (2006) Hospital-Based Strategies for Combating Resistance. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 42, S173-S181.
[24] Friedman, N.D., Kaye, K.S., Stout, J.E., McGarry, S.A., Trivette, S.L., Briggs, J.P., et al. (2002) Health Care—Associated Bloodstream Infections in Adults: A Reason to Change the Accepted Definition of Community-Acquired Infections. Annals of Internal Medicine, 137, 791-797.
[25] Ben-Ami, R., Schwaber, M.J., Navon-Venezia, S., Schwartz, D., Giladi, M., Chmelnitsky, I., et al. (2006) Influx of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae into the Hospital. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 42, 925-934.
[26] Birgand, G., Armand-Lefevre, L., Lolom, I., Ruppe, E., Andremont, A. and Lucet, J.C. (2013) Duration of Colonization by Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae after Hospital Discharge. American Journal of Infection Control, 41, 443-447.
[27] Kola, A., Holst, M., Chaberny, I.F., Ziesing, S., Suerbaum, S. and Gastmeier, P. (2007) Surveillance of Extended-Spectrum Beta-Lactamase-Producing Bacteria and Routine Use of Contact Isolation: Experience from a Three-Year Period. The Journal of Hospital Infection, 66, 46-51.
[28] Lohr, I.H., Rettedal, S., Natas, O.B., Naseer, U., Oymar, K. and Sundsfjord, A. (2013) Long-Term Faecal Carriage in Infants and Intra-Household Transmission of CTX-M-15-Producing Klebsiella pneumoniae Following a Nosocomial Outbreak. The Journal of Antimicrobial Chemotherapy, 68, 1043-1048.
[29] Tham, J., Walder, M., Melander, E. and Odenholt, I. (2012) Duration of Colonization with Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Patients with Travelers’ Diarrhoea. Scandinavian Journal of Infectious Diseases, 44, 573-577.
[30] Zahar, J.R., Lanternier, F., Mechai, F., Filley, F., Taieb, F., Mainot, E.L., et al. (2010) Duration of Colonisation by Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamase and Risk Factors for Persistent Faecal Carriage. The Journal of Hospital Infection, 75, 76-78.
[31] Strahilevitz, J., Jacoby, G.A., Hooper, D.C. and Robicsek, A. (2009) Plasmid-Mediated Quinolone Resistance: A Multifaceted Threat. Clinical Microbiology Reviews, 22, 664-689.
[32] Vetting, M.W., Park, C.H., Hegde, S.S., Jacoby, G.A., Hooper, D.C. and Blanchard, J.S. (2008) Mechanistic and Structural Analysis of Aminoglycoside N-Acetyltransferase AAC(6’)-Ib and Its Bifunctional, Fluoroquinolone-Active AAC(6’)-Ib-cr Variant. Biochemistry, 47, 9825-9835.
[33] van der Donk, C.F., Beisser, P.S., Hoogkamp-Korstanje, J.A., Bruggeman, C.A. and Stobberingh, E.E. (2011) A 12 Year (1998-2009) Antibiotic Resistance Surveillance of Klebsiella pneumoniae Collected from Intensive Care and Urology Patients in 14 Dutch Hospitals. The Journal of Antimicrobial Chemotherapy, 66, 855-858.
[34] Robberts, F.J., Kohner, P.C. and Patel, R. (2009) Unreliable Extended-Spectrum Beta-Lactamase Detection in the Presence of Plasmid-Mediated AmpC in Escherichia coli Clinical Isolates. Journal of Clinical Microbiology, 47, 358-361.
[35] Sundhedsstyrelsen (2012) Vejledning om ordination af antibiotika (Only in Danish).
[36] (2014) Folkh?lsomyndigheten ESBL-producerande tarmbakterier Kunskapsunderlag med förslag till handläggning för att begränsa spridningen av Enterobacteriaceae med ESBL.
[37] (WIP) TDWIP (2005) Measures to Prevent Transmission of Highly Resistant Microorganisms (HRMO).

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.