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-β-lactamase (NDM)-mediated carbapenem resistance has been identified in Enterobacteriaceae from numerous countries including those of the Indian subcontinent. Currently, seven NDM β-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 blaNDM-positive by PCR, but 13 isolates bore variants that differed in sequence from blaNDM-1. NDM-5, NDM-6 and NDM-7 were identified in two, eight and three isolates, respectively. blaNDM variants were located on plasmids of >100kb with IncF, IncA/C and untypeable replicon types. Genes encoding the 16S rRNA methyltransferases RmtB, RmtC and ArmA as well as those for AmpC β-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 blaNDM-1 and blaNDM variants [25% (11/44) vs. 23% (3/13)]. 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.
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India; Department of Biosciences, Integral University, Lucknow, India.
Mohibur
M
Rahman
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India.
Sanket Kumar
SK
Shukla
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India. Electronic address: kashinprasad@gmail.com.
Kashi Nath
KN
Prasad
Department of Animal Health and VISAVET, Universidad Complutense de Madrid, Madrid, Spain.
Cristina M
CM
Ovejero
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India.
Binod Kumar
BK
Pati
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India.
Aparna
A
Tripathi
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India.
Avinash
A
Singh
Department of Biosciences, Integral University, Lucknow, India.
Ashwini K
AK
Srivastava
Department of Animal Health and VISAVET, Universidad Complutense de Madrid, Madrid, Spain.
Bruno
B
Gonzalez-Zorn
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007194:India; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D010957:Plasmids / Q000378:metabolism*; D016019:Survival Analysis; D062606:Tertiary Care Centers; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D047090:beta-Lactams; D008780:Methyltransferases; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1
ESBL; Enterobacteriaceae; Metallo-β-lactamase; Methylase; NDM variants; NDM-1