Trends in Microbiology
ReviewThe emerging NDM carbapenemases
Section snippets
Worldwide epidemiology and clinical impact
NDM-1 (New Delhi metallo-β-lactamase-1) is the most-recently discovered transferable molecular class B (zinc metallo-) β-lactamase. It was first described in Klebsiella pneumoniae and Escherichia coli isolated in Sweden in 2008 from an Indian patient transferred one day previously from a New Delhi hospital [1]. Similar to other class B β-lactamases (e.g. IMP and VIM) and unlike class A, C and D β-lactamases, NDM-1 has zinc ions at its active site, not a serine residue 2, 3, 4. Also similar to
Genetics of NDM-1
The original source of the blaNDM-1 gene remains unknown, but it must be postulated to have been captured from its original chromosomal location by mobile DNA from some unknown (and doubtless innocuous) environmental organism. Clinical E. coli and K. pneumoniae with NDM-1 belong to a diversity of ST types [48], although multiple producers belonging to E. coli ST101 have been recovered in the UK, Pakistan and Canada; this could indicate an association, or it might simply be that ST101 is a
Biochemistry of NDM-1
NDM-1 shares little sequence identity with other acquired metallo-β-lactamases 1, 3. The most similar (or less different) metallo-β-lactamases are VIM-1/VIM-2, with which NDM-1 shares only 32.4% amino acid identity [1]. Nevertheless, similar to IMP and VIM types, NDM-1 is a monomeric metalloenzyme with a molecular mass of 28 kDa that hydrolyzes all β-lactams except the monobactam aztreonam [1]. This activity is not inhibited by commercially available β-lactamase inhibitors such as clavulanic
Resistance patterns of bacteria with NDM-1 enzyme
Most Enterobacteriaceae and A. baumannii with NDM-1 are resistant to wide ranges of β-lactam and non-β-lactam antibiotics, carrying even wider batteries of resistance genes than do producers of other carbapenemases such as the KPC and VIM types 5, 6, 16, 58.
Most clinical bacteria with NDM-1 remain susceptible in vitro only to colistin and to either or both of tigecycline and fosfomycin; however, K. pneumoniae with NDM-1 often has intermediate resistance to tigecycline and fosfomycin, and this
Identification and detection
To stem the onslaught of bacteria with NDM-1 and other potent carbapenemases, early identification of cases and carriers is mandatory, but is far from easy. Many strains with NDM-1 and other carbapenemases are clearly resistant in vitro, but this is not true of all 16, 59, 60 and it is plausible that the least resistant are the most often missed and are therefore the least represented in evaluations of detection methodology, even with the new, lowered EUCAST and CLSI breakpoints ([61]; //www.eucast.org/
Concluding remarks
Although most of the bacteria with NDM-1 seen in the West have been in hospitalized patients, some with complicated histories, it is of clear and particular concern that blaNDM-1 genes, carried by E. coli, have penetrated into the wider environment in India and Pakistan, and have been recovered from community-acquired infections, fecal flora and surface water [47]. It seems certain that this circulation is promoted by promiscuous plasmids carrying the gene among strains, by wide usage of
Acknowledgments
We thank many collaborators worldwide, particularly Thierry Naas, Mark Toleman and Neil Woodford, who have contributed to gain significant knowledge in this field. This work was funded by a grant from INSERM Unité 914, Paris, France.
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