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Carbapenem-Resistant Klebsiella pneumoniae Producing New Delhi Metallo-β-Lactamase at an Acute Care Hospital, Colorado, 2012

  • Erin E. Epson (a1) (a2), Larissa M. Pisney (a3), Joyanna M. Wendt (a1) (a4), Duncan R. MacCannell (a5), Sarah J. Janelle (a2), Brandon Kitchel (a4), J. Kamile Rasheed (a4), Brandi M. Limbago (a4), Carolyn V. Gould (a4), Alexander J. Kallen (a4), Michelle A. Barron (a3) and Wendy M. Bamberg (a2)...



To investigate an outbreak of New Delhi metallo-β-lactamase (NDM)–producing carbapenem-resistant Enterobacteriaceae (CRE) and determine interventions to interrupt transmission.

Design, Setting, and Patients.

Epidemiologic investigation of an outbreak of NDM-producing CRE among patients at a Colorado acute care hospital.


Case patients had NDM-producing CRE isolated from clinical or rectal surveillance cultures (SCs) collected during the period January 1, 2012, through October 20, 2012. Case patients were identified through microbiology records and 6 rounds of SCs in hospital units where they had resided. CRE isolates were tested by real-time polymerase chain reaction for bla NDM. Medical records were reviewed for epidemiologic links; relatedness of isolates was evaluated by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS). Infection control (IC) was assessed through staff interviews and direct observations.


Two patients were initially identified with NDM-producing CRE during July–August 2012. A third case patient, admitted in May, was identified through microbiology records review. SC identified 5 additional case patients. Patients had resided in 11 different units before identification. All isolates were highly related by PFGE. WGS suggested 3 clusters of CRE. Combining WGS with epidemiology identified 4 units as likely transmission sites. NDM-producing CRE positivity in certain patients was not explained by direct epidemiologic overlap, which suggests that undetected colonized patients were involved in transmission.


A 4-month outbreak of NDM-producing CRE occurred at a single hospital, highlighting the risk for spread of these organisms. Combined WGS and epidemiologic data suggested transmission primarily occurred on 4 units. Timely SC, combined with targeted IC measures, were likely responsible for controlling transmission.


Corresponding author

Epidemic Intelligence Service Officer, Colorado Department of Public Health and Environment, 4300 Cherry Creek Drive South, Denver CO 80246 (


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1. Johnson, AP, Woodford, N. Global spread of antibiotic resistance: the example of New Delhi metallo-beta-lactamase (NDM)-mediated carbapenem resistance. J Med Microbiol 2013;62:499513.
2. Yong, D, Toleman, MA, Giske, CG, et al. 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;53:50465054.
3. Nordmann, P, Naas, T, Poirel, L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17:17911798.
4. Wilson, ME, Chen, LH. NDM-1 and the role of travel in its dissemination. Curr Infect Dis Rep 2012;14:213226.
5. Centers for Disease Control and Prevention. Detection of Enterobacteriaceae isolates carrying metallo-beta-lactamase: United States, 2010. MMWR Morb Mortal Wkly Rep 2010;59:750.
6. Nordmann, P, Poirel, L, Walsh, TR, Livermore, DM. The emerging NDM carbapenemases. Trends Microbiol 2011;19:588595.
7. Centers for Disease Control and Prevention (CDC). Multiplex Real-Time PCR Detection of Klebsiella pneumoniae Carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM-1). Atlanta, Georgia: CDC, 2011. Accessed August 6, 2013.
8. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. Wayne, PA: CLSI, 2012. CLSI document M100-S22.
9. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement. Wayne, PA: CLSI, 2009. CLSI document M100-S19.
10. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically: Approved Standard. 9th ed. Wayne, PA: CLSI, 2012. CLSI document M07–M09.
11. Centers for Disease Control and Prevention (CDC). Laboratory Protocol for Detection of Carbapenem-Resistant or Carbapenemase-Producing Klebsiella spp. and E. coli from Rectal Swabs. Atlanta, Georgia: CDC, 2011. Accessed August 6, 2013.
12. Kitchel, B, Rasheed, JK, Patel, JB, et al. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob Agents Chemother 2009;53:33653370.
13. kSNP 2.0 ed. Livermore, California: Lawrence Livermore National Lab, 2013.
14. Gardner, SN, Hall, BG. When whole-genome alignments just won't work: kSNP v2 software for alignment-free SNP discovery and phylogenetics of hundreds of microbial genomes. PLOS ONE 2013;8(12):e81760.
15. Li, H, Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009;25:17541760.
16. Li, H, Handsaker, B, Wysoker, A, et al. The sequence alignment/map (SAM) format and SAMtools. Bioinformatics 2009;25:20782079.
17. Koboldt, D, Zhang, Q, Larson, D, et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 2012;22(3):568576.
18. Garrison, E, Marth, G. Haplotype-based variant detection from short-read sequencing, eprint arXiv: 12073907. 2012.
19. Tamura, K, Peterson, D, Peterson, N, Stecher, G, Nei, M, Kumar, S. MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011;28:27312739.
20. Centers for Disease Control and Prevention (CDC). New Carbapenem-Resistant Enterobacteriaceae Warrant Additional Action by Healthcare Providers. Atlanta, Georgia: CDC, 2013. Accessed August 6, 2013.
21. Borgia, S, Lastovetska, O, Richardson, D, et al. Outbreak of carbapenem-resistant Enterobacteriaceae containing blaNDM-1, Ontario, Canada. Clin Infect Dis 2012;55:e109e117.
22. Lowe, CF, Kus, JV, Salt, N, et al. Nosocomial transmission of New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae in Toronto, Canada. Infect Control Hosp Epidemiol 2013;34:4955.
23. Escobar Perez, JA, Olarte Escobar, NM, Castro-Cardozo, B, et al. Outbreak of NDM-1-producing Klebsiella pneumoniae in a neo-natal unit in Colombia. Antimicrob Agents Chemother 2013;57:19571960.
24. Centers for Disease Control and Prevention (CDC). 2012 CRE Toolkit: Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE). Atlanta, Georgia: CDC, 2012. Accessed August 6, 2013.
25. Snitkin, ES, Zelazny, AM, Thomas, PJ, et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 2012;4:148ra16.
26. Koser, CU, Holden, MT, Ellington, MJ, et al. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. New Engl J Med 2012;366:22672275.
27. Lewis, T, Loman, NJ, Bingle, L, et al. High-throughput whole-genome sequencing to dissect the epidemiology of Acinetobacter baumannii isolates from a hospital outbreak. J Hosp Infect 2010;75:3741.
28. Thurlow, CJ, Prabaker, K, Lin, MY, et al. Anatomic sites of patient colonization and environmental contamination with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae at long-term acute care hospitals. Infect Control Hosp Epidemiol 2013;34:5661.
29. Munoz-Price, LS, Quinn, JP. Deconstructing the infection control bundles for the containment of carbapenem-resistant Enterobacteriaceae. Curr Opin Infect Dis 2013;26:378387.
30. Charlson, ME, Pompei, P, Ales, KL, MacKenzie, CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373383.


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