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New Delhi metallo-?-lactamase-1: local acquisition in Ontario, Canada, and challenges in detection.

ABSTRACT: New Delhi metallo-?-lactamase-1 (NDM-1) is a recently identified metallo-?-lactamase that confers resistance to carbapenems and all other ?-lactam antibiotics, with the exception of aztreonam. NDM-1 is also associated with resistance to many other classes of antibiotics. The enzyme was first identified in organisms isolated from a patient in Sweden who had previously received medical treatment in India, but it is now recognized as endemic throughout India and Pakistan and has spread worldwide. The gene encoding NDM-1 has been found predominantly in Escherichia coli and Klebsiella pneumoniae. We describe the isolation NDM-1-producing organisms from two patients in Toronto, Ontario. To the best of our knowledge, this is the first report of an organism producing NDM-1 that was locally acquired in Canada. We also discuss the evidence that NDM-1 can affect bacterial species other than E. coli and K. pneumoniae, the limited options for treatment and the difficulty laboratories face in detecting organisms that produce NDM-1.

SUBMITTER: Kus JV

PROVIDER: S-EPMC3153514 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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New Delhi metallo-β-lactamase-1: local acquisition in Ontario, Canada, and challenges in detection.

Kus Julianne V JV Tadros Manal M Simor Andrew A Low Donald E DE McGeer Allison J AJ Willey Barbara M BM Larocque Cindy C Pike Karen K Edwards Iris-Ann IA Dedier Helen H Melano Roberto R Boyd David A DA Mulvey Michael R MR Louie Lisa L Okeahialam Christopher C Bayley Mark M Whitehead Cynthia C Richardson Denyse D Carr Lesley L Jinnah Fatema F Poutanen Susan M SM

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20110530 11

New Delhi metallo-β-lactamase-1 (NDM-1) is a recently identified metallo-β-lactamase that confers resistance to carbapenems and all other β-lactam antibiotics, with the exception of aztreonam. NDM-1 is also associated with resistance to many other classes of antibiotics. The enzyme was first identified in organisms isolated from a patient in Sweden who had previously received medical treatment in India, but it is now recognized as endemic throughout India and Pakistan and has spread worldwide. T ...[more]

PMID: 21624908

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Project description:BACKGROUND:New Delhi metallo-?-lactamase (bla NDM), a plasmid-borne carbapenemase gene associated with significant mortality and severely limited treatment options, is of global public health concern as it is found in extremely diverse Gram-negative bacterial strains. This study thus aims to genetically characterize local and global spread of bla NDM. METHODS:To investigate local transmission patterns in the context of a single hospital, whole genome sequencing data of the first 11 bla NDM-positive bacteria isolated in a local hospital were analyzed to: (1) identify and compare bla NDM-positive plasmids; and (2) study the phylogenetic relationship of the bacteria chromosomes. The global analysis was conducted by analyzing 2749 complete plasmid sequences (including 39 bla NDM-positive plasmids) in the NCBI database, where: (1) the plasmids were clustered based on their gene composition similarity; (2) phylogenetic study was conducted for each bla NDM-positive plasmid cluster to infer the phylogenetic relationship within each cluster; (3) gene transposition events introducing bla NDM into different plasmid backbones were identified; and (4) clustering pattern was correlated with the plasmids' incompatibility group and geographical distribution. RESULTS:Analysis of the first 11 bla NDM-positive isolates from a single hospital revealed very low bla NDM-positive plasmid diversity. Local transmission was characterized by clonal spread of a predominant plasmid with 2 sporadic instances of plasmid introduction. In contrast to the low diversity locally, global bla NDM spread involved marked plasmid diversity with no predominant bacterial clone. Thirty-nine (1.4 %) out of the 2749 complete plasmid sequences were bla NDM-positive, and could be resolved into 7 clusters, which were associated with plasmid incompatibility group and geographical distribution. The bla NDM gene module was witnessed to mobilize between different plasmid backbones on at least 6 independent occasions. CONCLUSIONS:Our analysis revealed the complex genetic pathways of bla NDM spread, with global dissemination characterized mainly by transposition of the bla NDM gene cassette into varied plasmids. Early local transmission following plasmid introduction is characterized by plasmid conjugation and bacterial spread. Our findings emphasize the importance of plasmid molecular epidemiology in understanding bla NDM spread.

Dataset Information

New Delhi metallo-?-lactamase-1: local acquisition in Ontario, Canada, and challenges in detection.

Publications

New Delhi metallo-β-lactamase-1: local acquisition in Ontario, Canada, and challenges in detection.

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