Skip to main content

Advertisement

Log in

Findings from an outbreak of carbapenem-resistant Klebsiella pneumoniae emphasize the role of antibiotic treatment for cross transmission

  • Original Paper
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

In January 2015, we noticed by rectal swab analyses that seven of 23 patients at an early rehabilitation ward had been colonized with carbapenem-resistant Klebsiella pneumoniae (CKP). Here, we describe risk factors for CKP acquisition.

Methods

In the present study, the outbreak is described and risk factors for CKP acquisition are examined, e.g., antibiotic treatment. Microbiological analyses including corresponding results were examined to study when colonization with CKP occurred and whether patients had suffered from diarrhea. To examine whether spread of bacteria was clonal, multi-locus sequence typing as well as Xbal macrorestriction and pulsed-field gel electrophoresis was performed. The presence of carbapenmase was examined by PCR analysis. Through univariate analysis of risk factors in the small study sample, the role of antibiotic consumption, isolation procedures, patient’s age, gender, and Barthel index on colonization was elucidated.

Results

Clonal spread of the novel sequence type (ST)2255 was identified. Additionally, one patient was colonized with Escherichia coli and Serratia marcescens, both resistant to carbapenems, while a further patient carried another carbapenem-resistant E. coli strain. In all isolates, carbapenemase gene bla OXA-48 was found to be located on a conjugative plasmid (60 kb), suggesting in vivo transmission from CKP to E. coli and S. marcescens. Univariate tests indicated that antibiotic treatment was the only risk factor showing a significant association with being colonized by CKP. In addition, the likelihood of diarrhea appeared to be higher in this group. Antibiotic treatment was associated with CKP colonization, whereas patients´ age, gender, Barthel index at admission, and residence with a CKP-colonized roommate were not. Diarrhea also seemed to support to distribution of CKP.

Conclusions

In this small outbreak, antibiotic treatment seemed to be the predominant risk factor for monoclonal transmission of bla OXA-48 positive CKP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Senda K, Arakawa Y, Ichiyama S, Nakashima K, Ito H, Ohsuka S, Shimokata K, Kato N, Ohta M. PCR detection of metallo-beta-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta-lactams. J Clin Microbiol. 2009;34:2909–13.

    Google Scholar 

  2. Bradford PA, Urban C, Mariano N, Projan SJ, Rahal JJ, Bush K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the loss of an outer membrane protein. Antimicrob Agents Chemother. 1997;41:563–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. MacKenzie FM, Forbes KJ, Dorai-John T, Amyes SG, Gould IM. Emergence of a carbapenem-resistant Klebsiella pneumoniae. Lancet. 1997;350:783.

    Article  CAS  PubMed  Google Scholar 

  4. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20:440–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;7:895. https://doi.org/10.3389/fmicb.2016.00895.

    PubMed  PubMed Central  Google Scholar 

  6. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53:5046–54. https://doi.org/10.1128/AAC.00774-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pfeifer Y, Schlatterer K, Engelmann E, Schiller RA, Frangenberg HR, Stiewe D, Holfelder M, Witte W, Nordmann P. Poirel L emergence of OXA-48-type carbapenemase-producing enterobacteriaceae in German hospitals. Antimicrob Agents Chemother. 2012;56:2125–8. https://doi.org/10.1128/AAC.05315-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kaase M, Schimanski S, Schiller R, Beyreiß B, Thürmer A, Steinmann J, Kempf VA, Hess C, Sobottka I, Fenner I, Ziesing S, Burckhardt I, von Müller L, Hamprecht A, Tammer I, Wantia N, Becker K, Holzmann T, Furitsch M, Volmer G, Gatermann SG. Multicentre investigation of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in German hospitals. Int J Med Microbiol. 2016;306:415–20. https://doi.org/10.1016/j.ijmm.2016.05.009.

    Article  CAS  PubMed  Google Scholar 

  9. Heudorf U, Büttner B, Hauri AM, Heinmüller P, Hunfeld KP, Kaase M, Kleinkauf N, Albert-Braun S, Tessmann R, Kempf VA. Carbapenem-resistant Gram-negative bacteria—analysis of the data obtained through a mandatory reporting system in the Rhine-Main region, Germany, 2012–2015. GMS Hyg Infect Control. 2016;11:Doc10. https://doi.org/10.3205/dgkh000270.

  10. Wendt C, Schütt S, Dalpke AH, Konrad M, Mieth M, Trierweiler-Hauke B, Weigand MA, Zimmermann S, Biehler K, Jonas D. First outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in Germany. Eur J Clin Microbiol Infect Dis. 2010;29:563–70. https://doi.org/10.1007/s10096-010-0896-0.

    Article  CAS  PubMed  Google Scholar 

  11. Lübbert C, Lippmann N, Busch T, Kaisers UX, Ducomble T, Eckmanns T, Rodloff AC. Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K. pneumoniae after a large single-center outbreak in Germany. Am J Infect Control. 2014;42:376–80. https://doi.org/10.1016/j.ajic.2013.12.001.

    Article  PubMed  Google Scholar 

  12. Kola A, Piening B, Pape UF, Veltzke-Schlieker W, Kaase M, Geffers C, Wiedenmann B, Gastmeier P. An outbreak of carbapenem-resistant OXA-48—producing Klebsiella pneumoniae associated to duodenoscopy. Antimicrob Resist Infect Control. 2015;4:8. https://doi.org/10.1186/s13756-015-0049-4.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Steger S, Demetz F, Schmidt C, Borgmann S. Low percentage of asylum seekers colonized with multi-resistant bacteria treated at a German hospital. Jacobs J Epidemiol Prev Med. 2016;2:021.

    Google Scholar 

  14. Empfehlungen zur Prävention und Kontrolle von Methicillinresistenten Staphylococcus aureus-Stämmen (MRSA) in medizinischen und pflegerischen Einrichtungen Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut. Bundesgesundheitsbl. 2014;57:696–732. https://doi.org/10.1007/s00103-014-1980-x.

  15. Mutters NT, Mersch-Sundermann V, Mutters R, Brandt C, Schneider-Brachert W, Frank U. Control of the spread of vancomycin-resistant enterococci in hospitals—epidemiology and clinical relevance. Dtsch Arztebl Int. 2013;110:725–31. https://doi.org/10.3238/arztebl.2013.0725.

    PubMed  PubMed Central  Google Scholar 

  16. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. Twenty-third Informational supplement, M100-S23. In: Wayne PA. Clinical and Laboratory Standards Institute; 2013. http://shop.clsi.org/site/Sample_pdf/M100S25_sample.pdf.

  17. Gröbner S, Linke D, Schütz W, Fladerer C, Madlung J, Autenrieth IB, Witte W, Pfeifer Y. Emergence of carbapenem-non-susceptible extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates at the university hospital of Tübingen, Germany. J Med Microbiol. 2009;58:912–22. https://doi.org/10.1099/jmm.0.005850-0.

    Article  PubMed  Google Scholar 

  18. Pfeifer Y, Matten J, Rabsch W. Salmonella enterica serovar Typhi with CTX-M beta-lactamase, Germany. Emerg Infect Dis. 2009;15:1533–5. https://doi.org/10.3201/eid1509.090567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pfeifer Y, Wilharm G, Zander E, Wichelhaus TA, Göttig S, Hunfeld KP, Seifert H, Witte W, Higgins PG. Molecular characterization of blaNDM-1 in an Acinetobacter baumannii strain isolated in Germany in 2007. J Antimicrob Chemother. 2011;66:1998–2001. https://doi.org/10.1093/jac/dkr256.

    Article  CAS  PubMed  Google Scholar 

  20. Aubert D, Naas T, Héritier C, Poirel L, Nordmann P. Functional characterization of IS1999, an IS4 family element involved in mobilization and expression of beta-lactam resistance genes. J Bacteriol. 2006;188:6506–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Carrër A, Poirel L, Yilmaz M, Akan OA, Feriha C, Cuzon G, Matar G, Honderlick P, Nordmann P. Spread of OXA-48-encoding plasmid in Turkey and beyond. Antimicrob Agents Chemother. 2010;54:1369–73. https://doi.org/10.1128/AAC.01312-09.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Doi Y, Arakawa Y. 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin Infect Dis. 2007;45:88–94.

    Article  CAS  PubMed  Google Scholar 

  23. Clowes RC, Rowley D. Some observations on linkage effects in genetic recombination in Escherichia coli K-12. J Gen Microbiol. 1954;11:2502–60.

    Google Scholar 

  24. Barton BM, Harding GP, Zuccarelli AJ. A general method for detecting and sizing large plasmids. Anal Biochem. 1995;226:235–40.

    Article  CAS  PubMed  Google Scholar 

  25. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Clermont O, Bonacorsi S, Bingen E. Rapid and simple determination of the Escherichia coli phylogenetic group. Appl Environ Microbiol. 2000;66:4555–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Diancourt L, Passet V, Verhoef J, Grimont PA, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol. 2005;43:4178–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brisse S, Passet V, Haugaard AB, Babosan A, Kassis-Chikhani N, Struve C, Decré D. wzi Gene sequencing, a rapid method for determination of capsular type for Klebsiella strains. J Clin Microbiol. 2013;51:4073–8. https://doi.org/10.1128/JCM.01924-13.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut (RKI) Hygienemaßnahmen bei Infektionen oder Besiedlung mit multiresistenten gramnegativen Stäbchen, KRINKO-Empfehlung, Bundesgesundheitsblatt 10/2012. Bundesgesundheitsblatt. 2012;55:1311–54.

  30. Cubero M, Cuervo G, Dominguez MÁ, Tubau F, Martí S, Sevillano E, Gallego L, Ayats J, Peña C, Pujol M, Liñares J, Ardanuy C. Carbapenem-resistant and carbapenem-susceptible isogenic isolates of Klebsiella pneumoniae ST101 causing infection in a tertiary hospital. BMC Microbiol. 2015;15:177. https://doi.org/10.1186/s12866-015-0510-9.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zarakolu P, Eser OK, Aladag E, Al-Zahrani IA, Day KM, Atmaca O, Boral B, Cakir B, Perry JD, Akova M. Epidemiology of carbapenem-resistant Klebsiella pneumoniae colonization: a surveillance study at a Turkish university hospital from 2009 to 2013. Diagn Microbiol Infect Dis. 2016;85:466–70. https://doi.org/10.1016/j.diagmicrobio.2016.05.012.

    Article  PubMed  Google Scholar 

  32. Robert Koch Institute. Plasmid-vermittelter Multispezies-Ausbruch mit Carbapenem-resistenten Enterobacteriaceae. Epidemiologisches Bulletin. 2014;47:455–9.

    Google Scholar 

  33. Gharbi M, Moore LS, Gilchrist M, Thomas CP, Bamford K, Brannigan ET, Holmes AH. Forecasting carbapenem resistance from antimicrobial consumption surveillance: lessons learnt from an OXA-48-producing Klebsiella pneumoniae outbreak in a West London renal unit. Int J Antimicrob Agents. 2015;46:150–6. https://doi.org/10.1016/j.ijantimicag.2015.03.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lippmann N, Lübbert C, Kaiser T, Kaisers UX, Rodloff AC. Clinical epidemiology of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2014;14:271–2. https://doi.org/10.1016/S1473-3099(14)70705-4.

    Article  PubMed  Google Scholar 

  35. Marcade G, Brisse S, Bialek S, Marcon E, Leflon-Guibout V, Passet V, Moreau R, Nicolas-Chanoine MH. The emergence of multidrug-resistant Klebsiella pneumoniae of international clones ST13, ST16, ST35, ST48 and ST101 in a teaching hospital in the Paris region. Epidemiol Infect. 2013;141:1705–12. https://doi.org/10.1017/S0950268812002099.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Sibylle Müller-Bertling, Kirstin Ganske and Christine Schmidt for excellent technical assistance and Carolyn Dumont Wack for language editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefan Borgmann.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The study has not been funded.

Ethical standards

The study does not contain clinical studies or patient data allowing conclusion to patients’ identity or individual clinical course. According to the ethics committee of the Bavarian medical association (Bayerische Landesärztekammer, http://www.blaek.de), having jurisdiction over medical matters in our state (Federal State Bavaria), ethics approval is not necessary.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 471 kb)

Supplementary material 2 (DOCX 85 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Borgmann, S., Pfeifer, Y., Becker, L. et al. Findings from an outbreak of carbapenem-resistant Klebsiella pneumoniae emphasize the role of antibiotic treatment for cross transmission. Infection 46, 103–112 (2018). https://doi.org/10.1007/s15010-017-1103-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-017-1103-3

Keywords

Navigation