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      Tackling the threat of antimicrobial resistance: from policy to sustainable action

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          Abstract

          Antibiotics underpin all of modern medicine, from routine major surgery through to caesarean sections and modern cancer therapies. These drugs have revolutionized how we practice medicine, but we are in a constant evolutionary battle to evade microbial resistance and this has become a major global public health problem. We have overused and misused these essential medicines both in the human and animal health sectors and this threatens the effectiveness of antimicrobials for future generations. We can only address the threat of antimicrobial resistance (AMR) through international collaboration across human and animal health sectors integrating social, economic and behavioural factors. Our global organizations are rising to the challenge with the recent World Health Assembly resolution on AMR and development of the Global Action plan but we must act now to avoid a return to a pre-antibiotic era.

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          Most cited references6

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          Challenges of antibacterial discovery.

          The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.
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            A new antibiotic kills pathogens without detectable resistance.

            Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.
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              Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing.

              The Gram-negative bacteria Klebsiella pneumoniae is a major cause of nosocomial infections, primarily among immunocompromised patients. The emergence of strains resistant to carbapenems has left few treatment options, making infection containment critical. In 2011, the U.S. National Institutes of Health Clinical Center experienced an outbreak of carbapenem-resistant K. pneumoniae that affected 18 patients, 11 of whom died. Whole-genome sequencing was performed on K. pneumoniae isolates to gain insight into why the outbreak progressed despite early implementation of infection control procedures. Integrated genomic and epidemiological analysis traced the outbreak to three independent transmissions from a single patient who was discharged 3 weeks before the next case became clinically apparent. Additional genomic comparisons provided evidence for unexpected transmission routes, with subsequent mining of epidemiological data pointing to possible explanations for these transmissions. Our analysis demonstrates that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission.
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                Author and article information

                Journal
                Philosophical Transactions of the Royal Society B: Biological Sciences
                Phil. Trans. R. Soc. B
                The Royal Society
                0962-8436
                1471-2970
                June 05 2015
                June 05 2015
                June 05 2015
                : 370
                : 1670
                : 20140082
                Affiliations
                [1 ]Department of Health, Office of the Chief Medical Officer, 79 Whitehall, London SW1A 2NS, UK
                [2 ]Research Department of Infection and Population Health, University College London, 222 Euston Road, London NW1 2DA, UK
                [3 ]North East Health Protection Team, Public Health England, Gallowgate, Newcastle-upon-Tyne NE1 4WH, UK
                [4 ]Genomics England, Queen Mary University of London, Dawson Hall, Charterhouse Square, London EC1M 6BQ, UK
                [5 ]Public Health, Epidemiology and Biostatistics, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
                Article
                10.1098/rstb.2014.0082
                25918440
                4bee0d4a-8f37-4d28-ac09-46d6d57edcd2
                © 2015

                https://royalsociety.org/journals/ethics-policies/data-sharing-mining/

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