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      Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Background

          Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-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.

          Findings

          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.

          Interpretation

          The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.

          Funding

          European Union, Wellcome Trust, and Wyeth.

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          Most cited references 22

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          The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria.

          From early this decade, Enterobacteriaceae that produce Klebsiella pneumoniae carbapenemases (KPC) were reported in the USA and subsequently worldwide. These KPC-producing bacteria are predominantly involved in nosocomial and systemic infections; although they are mostly Enterobacteriaceae, they can also be, rarely, Pseudomonas aeruginosa isolates. KPC beta lactamases (KPC-1 to KPC-7) confer decreased susceptibility or resistance to virtually all beta lactams. Carbapenems (imipenem, meropenem, and ertapenem) may thus become inefficient for treating enterobacterial infections with KPC-producing bacteria, which are, in addition, resistant to many other non-beta-lactam molecules, leaving few available therapeutic options. Detection of KPC-producing bacteria may be difficult based on routine antibiotic susceptibility testing. It is therefore crucial to implement efficient infection control measures to limit the spread of these pathogens.
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            Resistance plasmid families in Enterobacteriaceae.

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              CTX-M: changing the face of ESBLs in Europe.

              Since around 2000 - earlier in Poland and Spain and later in France and the UK - dramatic shifts have occurred in the prevalence and types of extended-spectrum beta-lactamases (ESBLs) in Europe. Before this watershed, most producers were nosocomial isolates, often Klebsiella spp. or Enterobacter spp. from specialist care units, and had mutant TEM or SHV ESBLs. Subsequently, CTX-M ESBLs have become dominant, with much greater penetration into Escherichia coli, and with many infections in 'complicated community' patients, usually with underlying disease, recent antibiotic usage, or healthcare contact. The degree of clonality among producers varies with the country, as does the enzyme type produced, with group 9 (CTX-M-9 and -14) enzymes dominant in Spain and group 1 enzymes (particularly CTX-M-3 and -15) dominant elsewhere. Irrespective of the particular enzyme, most producers are multiresistant. These changing patterns present major therapeutic and infection control challenges, with the public health intervention points unclear.
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                Author and article information

                Contributors
                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet Infectious Diseases
                Elsevier Science, The Lancet Pub. Group
                1473-3099
                1474-4457
                September 2010
                September 2010
                : 10
                : 9
                : 597-602
                Affiliations
                [a ]Department of Microbiology, Dr ALM PG IBMS, University of Madras, Chennai, India
                [b ]Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK
                [c ]Health Protection Agency Centre for Infections, London, UK
                [d ]Department of Microbiology, Shaukat Khanum Cancer Hospital, Lahore, Pakistan
                [e ]Department of Microbiology, Pandit B D Sharma PG Institute of Medical Sciences, Haryana, India
                [f ]Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
                [g ]Department of Pathology and Microbiology, The Aga Khan University, Karachi, Pakistan
                [h ]Department of Microbiology, Amrita Institute of Medical Sciences, Kerala, India
                [i ]University of Queensland Centre for Clinical Research, University of Brisbane, Herston, QLD, Australia
                [j ]Department of Microbiology, Apollo Gleneagles Hospital, Kolkata, India
                [k ]Department of Medical Microbiology, Northumbria Healthcare NHS Foundation Trust, Tyne and Wear, UK
                [l ]Department of Microbiology, Apollo Hospitals, Chennai, India
                [m ]Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
                Author notes
                [* ]Correspondence to: Prof Timothy R Walsh, Professor of Medical Microbiology and Antimicrobial Resistance, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK walshtr@ 123456cardiff.ac.uk
                Article
                LANINF70143
                10.1016/S1473-3099(10)70143-2
                2933358
                20705517
                © 2010 Elsevier Ltd. All rights reserved.

                This document may be redistributed and reused, subject to certain conditions.

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