Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study.
BACKGROUND
Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-beta-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK.


METHODS
Enterobacteriaceae isolates were studied from two major centres in India--Chennai (south India), Haryana (north India)--and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla(NDM-1) was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan.


RESULTS
We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries.


CONCLUSIONS
The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.
Kumarasamy
Karthikeyan K
KK
Department of Microbiology, Dr ALM PG IBMS, University of Madras, Chennai, India.
Toleman
Mark A
MA
Walsh
Timothy R
TR
Bagaria
Jay
J
Butt
Fafhana
F
Balakrishnan
Ravikumar
R
Chaudhary
Uma
U
Doumith
Michel
M
Giske
Christian G
CG
Irfan
Seema
S
Krishnan
Padma
P
Kumar
Anil V
AV
Maharjan
Sunil
S
Mushtaq
Shazad
S
Noorie
Tabassum
T
Paterson
David L
DL
Pearson
Andrew
A
Perry
Claire
C
Pike
Rachel
R
Rao
Bhargavi
B
Ray
Ujjwayini
U
Sarma
Jayanta B
JB
Sharma
Madhu
M
Sheridan
Elizabeth
E
Thirunarayan
Mandayam A
MA
Turton
Jane
J
Upadhyay
Supriya
S
Warner
Marina
M
Welfare
William
W
Livermore
David M
DM
Woodford
Neil
N
D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics*; D004756:Enterobacteriaceae Infections / Q000453:epidemiology*; D006801:Humans; D007194:India / Q000453:epidemiology; D010154:Pakistan / Q000453:epidemiology; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D014195:Travel; D006113:United Kingdom / Q000453:epidemiology