New Delhi Metallo-β-Lactamase–producing Enterobacteriaceae, United States

J. Kamile Rasheed

, Brandon Kitchel, Wenming Zhu, Karen F. Anderson, Nancye C. Clark, Mary Jane Ferraro, Patrice Savard, Romney M. Humphries, Alexander J. Kallen, and Brandi M. Limbago

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (J.K. Rasheed, B. Kitchel, W. Zhu, K.F. Anderson, N.C. Clark, A.J. Kallen, B.M. Limbago); Massachusetts General Hospital, Boston, Massachusetts, USA (M.J. Ferraro); Johns Hopkins University, Baltimore, Maryland, USA (P. Savard); Johns Hopkins Health System, Baltimore (P. Savard); University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA (R.M. Humphries)

Abstract

We characterized 9 New Delhi metallo-β-lactamase–producing Enterobacteriaceae (5 Klebsiella pneumoniae, 2 Escherichia coli, 1 Enterobacter cloacae, 1 Salmonella enterica serovar Senftenberg) isolates identified in the United States and cultured from 8 patients in 5 states during April 2009–March 2011. Isolates were resistant to β-lactams, fluoroquinolones, and aminoglycosides, demonstrated MICs ≤1 µg/mL of colistin and polymyxin, and yielded positive metallo-β-lactamase screening results. Eight isolates had bla_NDM-1, and 1 isolate had a novel allele (bla_NDM-6). All 8 patients had recently been in India or Pakistan, where 6 received inpatient health care. Plasmids carrying bla_NDM frequently carried AmpC or extended spectrum β-lactamase genes. Two K. pneumoniae isolates and a K. pneumoniae isolate from Sweden shared incompatibility group A/C plasmids with indistinguishable restriction patterns and a common bla_NDM fragment; all 3 were multilocus sequence type 14. Restriction profiles of the remaining New Delhi metallo-β-lactamase plasmids, including 2 from the same patient, were diverse.

During the past decade, there has been an emergence of carbapenem-resistant Enterobacteriaceae that produce carbapenemases, enzymes that efficiently hydrolyze carbapenems, as well as most β-lactam drugs (1). The most common carbapenemase among Enterobacteriaceae in the United States is the Ambler class A Klebsiella pneumoniae carbapenemase (KPC), an enzyme that is found throughout the United States and globally (2,3). The emergence of another group of carbapenemases, the Ambler class B metallo-β-lactamases (MBLs), is of great concern worldwide (4). Until recently, MBLs were rarely identified in the United States and were found exclusively in Pseudomonas aeruginosa (5). However, recent reports of producing IMP– and VIM-type MBLs K. pneumoniae (6,7) have increased concerns over additional transmissible carbapenem resistance mechanisms in Enterobacteriaceae.
Among the most recent carbapenemases to appear in the United States is the newly described New Delhi MBL (NDM) (8–12). First reported in 2009, NDM-1 was initially identified in K. pneumoniae and Escherichia coli clinical isolates obtained from a Swedish patient who had been hospitalized in India (13). Drug-resistant gram-negative bacteria that produce NDM have been found in community and health care settings in India and Pakistan in a wide range of gram-negative genera containing diverse bla_NDM-harboring plasmids, and have been reported in >15 countries worldwide (4,14,15). The widespread dissemination of NDM-producing isolates and the apparent ease of mobility of bla_NDM is a major threat to public health on a global scale.
To complement reports of individual cases (8,10,12), we performed extensive laboratory characterization of 9 clinical isolates of NDM-producing Enterobacteriaceae collected from patients in the United States during April 2009–March 2011. Strain typing and plasmid restriction analysis were performed to identify common lineages. We also describe a novel NDM-encoding allele, designated bla_NDM-6.