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Volume 17, Number 2—February 2011

Letter

New Delhi Metallo-β-Lactamase, Ontario, Canada

Suggested citation for this article

To the Editor: The New Delhi metallo-β-lactamase (NDM-1) was first characterized in 2009 from Klebsiella pneumoniae and Escherichia coli isolated from a patient in Sweden who had received medical care in New Delhi, India (1). Further studies have shown broad dissemination of this β-lactamase gene (blaNDM-1) in India, Pakistan, Bangladesh, and the United Kingdom (2). Additional isolates have been detected in other countries, and many of the patients with NDM-1–producing Enterobacteriaceae reported receiving medical care in the Indian subcontinent (17). We describe detection and characterization of an NDM-1–producing K. pneumoniae isolated in Ontario, Canada.

In August 2010, a urinary tract infection was diagnosed in a 36-year-old woman in a hospital in Brampton, Ontario. An E. coli strain sensitive to multiple antibacterial drugs (including carbapenems) was isolated from a midstream urine sample; the patient was successfully treated with ciprofloxacin. One week after treatment, when the patient did not have a fever or other clinical signs, a urine culture was repeated, and a carbapenem-resistant K. pneumoniae isolate (GN529) was recovered. Travel history indicated that the patient had recently returned from India, where in mid-July she had had a miscarriage and had been hospitalized in Mumbai for 2 days. At that time, no antimicrobial drug treatment was prescribed.

Susceptibility profiles of K. pneumoniae GN529 and its E. coli transconjugant were obtained by using Etest (bioMérieux, Marcy l’Etoile, France) and the agar dilution method based on the Clinical and Laboratory Standards Institute guidelines (8). Multilocus sequence typing (MLST) of isolate GN529 was performed as described (9). The Pasteur Institute online database (www.pasteur.fr/recherche/genopole/PF8/mlst/Kpneumoniae.html) was used to assign the allelic numbers and sequence type (ST).

To screen for the most commonly known β-lactamase genes in enterobacteria, we performed multiplex PCRs (10). Primers were designed (NDM-F, 5′-AATGGAATTGCCCAATATTATGC-3′; NDM-R, 5′-CGAAAGTCAGGCTGTGTTG C-3′) for the specific detection of blaNDM-1 and included in 1 of the multiplex PCRs (multiplex V). Primers NDM-F and NDM-R2 (5′-TCAGCGCAGCTTGTCGGC-3′) were used to amplify and sequence the entire blaNDM-1 gene. The samples were screened for the presence of six 16S methylase genes (armA, rmtA–D, and npmA) by PCR. E. coli J53 transconjugants were selected on Luria-Bertani plates containing sodium azide and meropenem (100 µg/mL and 1 µg/mL, respectively). The plasmid harboring blaNDM-1 was identified by Southern blot analysis by using a specific digoxigenin-labeled blaNDM-1 probe (Roche Diagnostics, Indianapolis, IN, USA).

K. pneumoniae GN529 was highly resistant to all β-lactams, aminoglycosides, quinolones, tetracycline, nitrofurantoin, and co-trimoxazole. MICs of 0.5 µg/mL for colistin (European Committee on Antimicrobial Susceptibility Testing colistin breakpoint for Enterobacteriaceae: susceptibility <2 μg/mL) and 1 μg/mL for tigecycline (European Committee on Antimicrobial Susceptibility Testing and US Food and Drug Administration tigecycline breakpoint for Enterobacteriaceae: susceptibility <1 and <2 μg/mL, respectively) were also obtained (Table).

Considering the travel history of the patient and the high level resistance to all β-lactams, molecular screening of β-lactamases in strain GN529 was initiated to identify possible carbapenemases (e.g., blaNDM-1) in that isolate. Five β-lactamases genes (blaNDM, blaSHV, blaTEM, group 1 blaCTX-M , and blaOXA) and one 16S rRNA methylase (armA) were detected. By using primers for amplification of complete genes, we obtained sequences of blaNDM-1, 2 extended-spectrum β-lactamases (blaCTX-M-15 and blaSHV-12), 3 broad-spectrum β-lactamases (blaSHV-11, blaTEM-1 and blaOXA-1), and methyltransferase armA. No AmpC β-lactamases were linked to this isolate. Southern blotting identified a plasmid of ≈150 kb harboring blaNDM-1 (data not shown). A transconjugant E. coli positive for blaNDM-1 (E. coli J529, Table) was resistant to all β-lactams and aminoglycosides tested. In addition, blaSHV-12 and armA were detected in strain J529 (Table), indicating the potential for the horizontal spread of these resistance genes.

K. pneumoniae GN529 was typed by MLST as ST147, the same type as a clinical NDM-1–producing strain isolated in Australia (6) but distinct from ST14 and ST16 strains described (1,7). There are insufficient MLST data to confirm polyclonal dissemination of NDM-1, but previous pulsed-field gel electrophoresis results support that hypothesis (2).

K. pneumoniae GN529 was isolated from a patient who had recently received emergency medical care in India, suggesting importation of this clinical strain. In the United Kingdom, where Enterobacteriaceae containing blaNDM-1 are increasingly common, carriage of these organisms has been closely linked to receipt of medical care in the Indian subcontinent (2). Similar association as a risk factor was observed in other regions, including blaNDM-1-positive clinical strains isolated in North America, Australia, and Africa (36,10).

The NDM-1–producing enterobacteria described in this study previously had low MICs only for colistin and tigecycline (1,2,5,6). However, an NDM-1 isolate resistant to these antimicrobial drugs has also been described (2). Early detection and implementation of infection control interventions is essential for preventing the spread of multidrug-resistant organisms such as these. It may be prudent to consider medical exposure in the Indian subcontinent as a risk factor for possible infection, colonization, or both with multidrug-resistant, NDM-1–producing Enterobacteriaceae.

Nathalie Tijet, David C. Alexander, David Richardson, Olga Lastovetska, Donald E. Low, Samir N. Patel, and Roberto G. MelanoComments to Author 
Author affiliations: Author affiliations: Ontario Agency for Health Protection and Promotion, Toronto, Ontario, Canada (N. Tijet, D.C. Alexander, O. Lastovetska, D.E. Low, S.N. Patel, R.G. Melano); University of Toronto, Toronto (D.C. Alexander, O. Lastovetska, D.E. Low, S.N. Patel); William Osler Health Centre, Brampton Civic Hospital, Brampton, Ontario, Canada (D. Richardson); Mount Sinai Hospital, Toronto (D.E. Low, R.G. Melano)

Acknowledgment

We thank Prasad Rawte, Stephen Lo, Heather Siebert, Jennifer Ma, and Keisha Warren for technical support.

References

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  2. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Emergence of a new antibiotic resistance in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10:597602. DOIPubMed
  3. Centers for Disease Control and Prevention. Detection of Enterobacteriaceae isolates carrying metallo-β-lactamase—United States, 2010. MMWR Morb Mortal Wkly Rep. 2010;59:750.PubMed
  4. Poirel L, Lagrutta E, Taylor P, Pham J, Nordmann P. Emergence of metallo-β-lactamase NDM-1–producing multidrug resistant Escherichia coli in Australia. Antimicrob Agents Chemother. 2010;54:49146. DOIPubMed
  5. Poirel L, Revathi G, Bernabeu S, Nordmann P. Emergence of metallo-β-lactamase NDM-1 producing Klebsiella pneumoniae in Kenya. In: Abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; Boston; 2010 Sep 12–15; Abstract C1–1334. Washington: American Society of Microbiology; 2010.
  6. Sidjabat HE, Nimmo GR, Binotto E, Enbom R, George N, Paterson DL. A new threat from carbapenem resistant Klebsiella pneumoniae—the New Delhi metallo-β-lactamase (NDM-1). In: Abstracts of the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; Boston; 2010 Sep 12–15. Abstract C1–1332. Washington: American Society of Microbiology; 2010.
  7. Mulvey MR, Grant JM, Plewes K, Roscoe D, Boyd DA. New Delhi metallo-β-lactamase in Klebsiella pnemoniae and Escherichia coli, Canada. Emerg Infect Dis. 2011 Feb; [Epub ahead of print]. .DOI
  8. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 20th Informational supplement M100–S20. Wayne (PA): The Institute; 2010.
  9. Diancourt L, Passet V, Verhoef J, Grimont PAD, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol. 2005;43:417882. DOIPubMed
  10. Dallenne C, Da Costa A, Decre D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. J Antimicrob Chemother. 2010;65:4905. DOIPubMed

Table

Suggested citation for this article: Tijet N, Alexander DC, Richardson D, Lastovetska O, Low DE, Patel SN, et al. New Delhi metallo-β-lactamase, Ontario, Canada [letter]. Emerg Infect Dis [serial on the Internet]. 2011 Feb [date cited]. http://dx.doi.org/10.3201/eid1702.101561

DOI: 10.3201/eid1702.101561

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Table of Contents – Volume 17, Number 2—February 2011

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Roberto G. Melano, Ontario Agency for Health Protection and Promotion, Public Health Laboratory Branch, 81 Resources Rd, Toronto, Ontario M9P 3T1, Canada

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