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

PMID: 20705517 Related Articles

Authors: Kumarasamy, Karthikeyan K, Toleman, Mark A, Walsh, Timothy R, Bagaria, Jay, Butt, Fafhana, Balakrishnan, Ravikumar, Chaudhary, Uma, Doumith, Michel, Giske, Christian G, Irfan, Seema, Krishnan, Padma, Kumar, Anil, Maharjan, Sunil, Mushtaq, Shazad, Noorie, Tabassum, Paterson, David L, Pearson, Andrew, Perry, Claire, Pike, Rachel, Rao, Bhargavi, Ray, Ujjwayini, Sarma, Jayanta B, Sharma, Madhu, Sheridan, Elizabeth, Thirunarayan, Mandayam A, Turton, Jane, Upadhyay, Supriya, Warner, Marina, Welfare, William, Livermore, David M, Woodford, Neil

Journal: The Lancet infectious diseases, 2010

Abstract: 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. 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.

Affiliation: Department of Microbiology, Dr ALM PG IBMS, University of Madras, Chennai, India.

Wikipedia: Anti-bacterial agents, Antibiotic Resistance, Antibiotics, Aspergillus nuclease S1, B-DNA, Carbapenem antibiotics, Carbapenems, Cistron, Client, Colistin, Colistin sulfate, Coly-mycin, Common Market, DAEC, DNA, Deoxyribonucleic Acid, Double-stranded DNA, EAEC, EEC, EIEC, E Coli, Electrophoresis, Electrophoresis, gel, pulsed-field, Enteric bacteria, Enterobacteria, Enterobacteriaceae, Enteroinvasive Escherichia coli, Epidemiological study, Episome, Escherichia, Escherichia Coli, Euratom, European Atomic Energy Community, European Coal and Steel Community, European Common Market, European Community, European Economic Community, European Union, Gene, Genetic material, Genome, Genomics, Hospital, Hospitalization, India, Inverse PCR, Inverse polymerase chain reaction, Isotachophoresis, Klebsiella, Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Laboratories, Laboratory, Nested PCR, Nested polymerase chain reaction, PCR, Pakistan, Patient, Plasmid, Pneumonia, Pneumonitis, Polymerase Chain Reaction, Polymyxin E, Prevalence, Public Health, Pulsed field gel electrophoresis, S1 nuclease, Trust

Proteins: beta-lactamase 1, 111, S1, 36

Title: Detection of Enterobacteriaceae isolates carrying metallo-beta-lactamase - United States, 2010.

PMID: 20577157 Related Articles

Authors: centers for disease control and prevention (cdc)

Journal: MMWR. Morbidity and mortality weekly report, Vol. 59 (24): 750, 2010

Abstract: During January-June 2010, three Enterobacteriaceae isolates carrying a newly described resistance mechanism, the New Delhi metallo-beta-lactamase (NDM-1), were identified from three U.S. states at the CDC antimicrobial susceptibility laboratory. This is the first report of NDM-1 in the United States, and the first report of metallo-beta-lactamase carriage among Enterobacteriaceae in the United States. These isolates, which include an Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, carry blaNDM-1, which confers resistance to all beta-lactam agents except aztreonam (a monobactam antimicrobial); all three isolates were aztreonam resistant, presumably by a different mechanism. In the United Kingdom, where these organisms are increasingly common, carriage of Enterobacteriaceae containing blaNDM-1 has been closely linked to receipt of medical care in India and Pakistan. All three U.S. isolates were from patients who received recent medical care in India.

Pubmed MeSH: Aged, Carbapenems, Drug Resistance, Bacterial, Humans, beta-Lactamases

Wikipedia: Azactam, Aztreonam, Beta-lactams, CDC, Center for Disease Control, Center for Disease Control and Prevention, Centers For Disease Control, Centers For Disease Control And Prevention, Client, Cloaca, DAEC, EAEC, EIEC, E Coli, Enteric bacteria, Enterobacter, Enterobacter cloacae, Enterobacteria, Enterobacteriaceae, Enteroinvasive Escherichia coli, Escherichia, Escherichia Coli, Great Britain, India, Isle of Man, Klebsiella, Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Laboratories, Laboratory, Monobactams, Pakistan, Patient, Pneumonia, Pneumonitis, UNited Kingdom, UNited States, United States Centers for Disease Control, United States Centers for Disease Control and Prevention

Protein: beta-lactamase

Title: Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India.

PMID: 19770275 Related Articles

Authors: Yong, D, Toleman, M A, Giske, C G, Cho, H S, Sundman, K, Lee, K, Walsh, T R

Journal: Antimicrobial agents and chemotherapy, Vol. 53 (12): 5046-54, 2009

Abstract: A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.

Affiliation: Yonsei University College of Medicine, Research Institute of Antimicrobial Resistance, Seoul, Republic of Korea.

Pubmed MeSH: Amino Acid Sequence, Carboxylic Ester Hydrolases, Drug Resistance, Multiple, Bacterial, Electrophoresis, Gel, Pulsed-Field, Humans, Kinetics, Klebsiella Infections, Microbial Sensitivity Tests, Sequence Analysis, DNA, Sequence Homology, Amino Acid, beta-Lactamases

Wikipedia: Active site, Anti-bacterial agents, Antibiotic Resistance, Antibiotics, Azactam, Aztreonam, B-DNA, Beta-lactams, Binding site, Carbapenem antibiotics, Carbapenems, Cefalotin, Cefotaxime, Cefotaxime sodium, Cefuroxime, Cephalosporins, Cephalothin, Cistron, Claforan, Client, Colistin, Colistin sulfate, Coly-mycin, DAEC, DNA, DNA library, Deoxyribonucleic Acid, Double-stranded DNA, EAEC, EIEC, E Coli, Enteroinvasive Escherichia coli, Episome, Erythromycin, Erythromycin A, Escherichia, Escherichia Coli, Esterases, Feces, Fluoroquinolones, Gene, Gene library, Genetic material, Genetic structure, Ilotycin, India, Integron, Keflin, Kendrick, Klebsiella, Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Patient, Penicillin, Plasmid, Pneumonia, Pneumonitis, Polymyxin E, Urinary Tract Infection, Urinary tract, Zinacef

Proteins: esterase, beta-lactamase, arr-2, MBL, IMP-1

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