Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India

The growing prevalence of carbapenem resistance in Enterobacteriaceae worldwide is a major concern. New Delhi metallo-p-lactamase (NDM)-mediated carbapenem resistance has been identified in Enterobacteriaceae from numerous countries including those of the Indian subcontinent. Currently, seven NDM p-lactamase variants (NDM-1 to -7) have been identified. This study evaluated the detection and molecular characterisation of NDM variants in Enterobacteriaceae at a tertiary care hospital in India. A total of 464 isolates were tested; 57 (12.3%) were resistant or showed reduced susceptibility to imipenem and meropenem. All carbapenem-resistant isolates were bla(NDm)-positive by PCR, but 13 isolates bore variants that differed in sequence from bla(NDm-1). NDM-5, NDM-6 and NDM-7 were identified in two, eight and three isolates, respectively. bla(NDm) variants were located on plasmids of >100 kb with IncF, IncA/C and untypeable replicon types. Genes encoding the 16S rRNA methyltransferases RmtB, RmtC and ArmA as well as those for AmpC beta-lactamases were also located on the same plasmids as blaNDm in different combinations. The prevalence of NDM-5 to -7 variants was significantly higher in Escherichia coli (P=0.015) and they were more frequently isolated from the urology ward (P=0.037) than NDM-1. The mortality rate was comparable between patients infected with isolates positive for bla(NDm-1) and bla(NDm) variants [25% (11144) vs. 23% (31/3)]. Expression of blaNDm variants in E. coli using the same promoter showed that NDM-7 conferred higher resistance to imipenem. The diverse genotypic features of blaNDm indicate rapid evolution of NDM resulting from their wide spread in the Indian subcontinent. (C) 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.