Does broad-spectrum beta-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gram-negative bacteria?

The NDM-1 gene, first identified in Sweden in 2008 in Klebsiella pneumoniae from a patient hospitalized in New Delhi, encodes a metallo-β-lactamase that inactivates all β-lactams except aztreonam. This bla(NDM-1) gene has been identified in hospital-acquired bacterial species, such as K. pneumoniae, but also in the typical community-acquired species, Escherichia coli. This gene has been identified in strains that possess other resistance mechanisms contributing to their multidrug resistance patterns. It has been recently extensively reported from the UK, India and Pakistan and, albeit to a lesser extent, from a number of other countries worldwide. In most of the cases a link with the Indian subcontinent has also been established. To stem the onslaught of NDM producers, early identification of cases of NDM-related infections and prevention of their spread by implementing screening, hygiene measures and the isolation of carriers is needed.

[1]  Timothy R. Walsh,et al.  Metallo-β-Lactamases: the Quiet before the Storm? , 2005, Clinical Microbiology Reviews.

[2]  M. Chu,et al.  Carbapenemases in Enterobacteria, Hong Kong, China, 2009 , 2011, Emerging infectious diseases.

[3]  P. Nordmann,et al.  How To Detect NDM-1 Producers , 2010, Journal of Clinical Microbiology.

[4]  P. Nordmann,et al.  Detection of NDM-1-Producing Klebsiella pneumoniae in Kenya , 2010, Antimicrobial Agents and Chemotherapy.

[5]  F. Kapadia,et al.  New Delhi Metallo-beta lactamase (NDM-1) in Enterobacteriaceae: treatment options with carbapenems compromised. , 2010, The Journal of the Association of Physicians of India.

[6]  N. Woodford,et al.  Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study , 2010, The Lancet. Infectious diseases.

[7]  P. Nordmann,et al.  NDM-1-Producing Escherichia coli in Germany , 2010, Antimicrobial Agents and Chemotherapy.

[8]  P. Nordmann,et al.  Biochemical analysis of the ceftazidime-hydrolysing extended-spectrum beta-lactamase CTX-M-15 and of its structurally related beta-lactamase CTX-M-3. , 2002, The Journal of antimicrobial chemotherapy.

[9]  P. Krishnan,et al.  Coexistence of blaOXA-23 with blaNDM-1 and armA in clinical isolates of Acinetobacter baumannii from India. , 2010, The Journal of antimicrobial chemotherapy.

[10]  A. Fluit,et al.  Global spread of New Delhi metallo-β-lactamase 1. , 2010, The Lancet. Infectious diseases.

[11]  T. Wichelhaus,et al.  Global spread of New Delhi metallo-β-lactamase 1. , 2010, The Lancet. Infectious diseases.

[12]  P. Nordmann,et al.  NDM-1-producing Klebsiella pneumoniae isolated in the Sultanate of Oman. , 2011, The Journal of antimicrobial chemotherapy.

[13]  P. Nordmann,et al.  Extremely Drug-Resistant Citrobacter freundii Isolate Producing NDM-1 and Other Carbapenemases Identified in a Patient Returning from India , 2010, Antimicrobial Agents and Chemotherapy.

[14]  P. Nordmann,et al.  Addressing the challenge of extended-spectrum beta-lactamases. , 2009, Current opinion in investigational drugs.

[15]  E. Leitner,et al.  Emergence of New Delhi Metallo-β-Lactamase, Austria , 2011, Emerging infectious diseases.

[16]  P. Nordmann,et al.  Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. , 2001, FEMS microbiology letters.

[17]  P. Nordmann,et al.  Emergence of Metallo-β-Lactamase NDM-1-Producing Multidrug-Resistant Escherichia coli in Australia , 2010, Antimicrobial Agents and Chemotherapy.

[18]  Detection of Enterobacteriaceae isolates carrying metallo-beta-lactamase - United States, 2010. , 2010, MMWR. Morbidity and mortality weekly report.

[19]  P. Nordmann,et al.  International Transfer of NDM-1-Producing Klebsiella pneumoniae from Iraq to France , 2011, Antimicrobial Agents and Chemotherapy.

[20]  Timothy R. Walsh,et al.  Characterization of a New Metallo-β-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India , 2009, Antimicrobial Agents and Chemotherapy.

[21]  M. Mulvey,et al.  New Delhi Metallo-β-Lactamase in Klebsiella pneumoniae and Escherichia coli, Canada , 2011, Emerging infectious diseases.

[22]  A. Sundsfjord,et al.  Identification of NDM-1-producing Enterobacteriaceae in Norway. , 2011, The Journal of antimicrobial chemotherapy.

[23]  M. Toleman,et al.  Global spread of New Delhi metallo-β-lactamase 1. , 2010, The Lancet. Infectious diseases.

[24]  H. Leong,et al.  Global spread of New Delhi metallo-β-lactamase 1. , 2010, The Lancet. Infectious diseases.

[25]  Shou-Dong Lee,et al.  First identification of a patient colonized with Klebsiella pneumoniae carrying blaNDM-1 in Taiwan. , 2010, Journal of the Chinese Medical Association : JCMA.

[26]  D. Paterson,et al.  Emergence of High Levels of Extended-Spectrum-β-Lactamase-Producing Gram-Negative Bacilli in the Asia-Pacific Region: Data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) Program, 2007 , 2009, Antimicrobial Agents and Chemotherapy.

[27]  P. Nordmann,et al.  Global spread of New Delhi metallo-β-lactamase 1. , 2010, The Lancet. Infectious diseases.

[28]  T. Esemenli,et al.  Sweating: a formidable challenge in orthopaedic surgery. , 2010, The Journal of hospital infection.

[29]  A. Muir,et al.  New Delhi metallo-beta-lactamase: a cautionary tale. , 2010, The Journal of hospital infection.

[30]  P. Nordmann,et al.  Diversity, Epidemiology, and Genetics of Class D β-Lactamases , 2009, Antimicrobial Agents and Chemotherapy.

[31]  P. Nordmann,et al.  The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. , 2009, The Lancet. Infectious diseases.