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Authors: Pecora, Nicole and Zhao, Xiaomin and Nudel, Kathleen and Hoffmann, Maria and Li, Ning and Onderdonk, Andrew B and Yokoe, Deborah and Brown, Eric and Allard, Marc and Bry, Lynn

New Delhi metallo-beta-lactamases (NDMs) are an uncommon but emerging cause of carbapenem resistance in the United States. Genomic factors promoting their domestic spread remain poorly characterized. A prospective genomic surveillance program among Boston-area hospitals identified multiple new occurrences of NDM carrying strains of E. coli and E. cloacae complex in inpatient and outpatient settings, representing the first occurrences of NDM-mediated resistance since initiating genomic surveillance in 2011. Cases included domestic patients with no international exposures. PacBio sequencing of isolates identified strain characteristics, resistance genes, and the complement of mobile vectors mediating spread. Analyses revealed a common 3114-bp region containing the blaNDM gene, with carriage of this conserved region among unique strains by diverse transposon and plasmid backbones. Functional studies revealed broad capacity for blaNDM transmission by conjugation, transposition, and complex inter-plasmid recombination events. NDMs represent a rapidly spreading form of drug resistance that can occur in inpatient and outpatient settings and in patients without international exposures. In contrast to Tn4401-based spread of Klebsiella pneumoniae carbapenemases (KPCs), diverse transposable elements mobilize NDM enzymes, commonly with other resistance genes, enabling naïve strains to acquire multi- and extensively-drug resistance profiles with single transposition or plasmid conjugation events. Genomic surveillance provides effective means to rapidly identify these gene-level drivers of resistance and mobilization, to inform clinical decisions to prevent further spread. Copyright © 2018 American Society for Microbiology.

Journal: Antimicrobial agents and chemotherapy
DOI: 10.1128/AAC.02040-18
Year: 2018

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