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      A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future

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          Abstract

          This article gives a very brief overview of the antibiotic era, beginning from the discovery of first antibiotics until the present day situation, which is marred by the emergence of hard-to-treat multiple antibiotic-resistant infections. The ways of responding to the antibiotic resistance challenges such as the development of novel strategies in the search for new antimicrobials, designing more effective preventive measures and, importantly, better understanding the ecology of antibiotics and antibiotic resistance are discussed. The expansion of conceptual frameworks based on recent developments in the field of antimicrobials, antibiotic resistance, and chemotherapy is also discussed.

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          Most cited references 70

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          Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.

          Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
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            Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

            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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              Drugs for bad bugs: confronting the challenges of antibacterial discovery.

              The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
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                Author and article information

                Journal
                Front Microbiol
                Front. Microbio.
                Frontiers in Microbiology
                Frontiers Research Foundation
                1664-302X
                29 October 2010
                08 December 2010
                2010
                : 1
                Affiliations
                1simpleRowett Institute of Nutrition and Health, University of Aberdeen Aberdeen, UK
                Author notes

                Edited by: Jose L. Martinez, Centro Nacional de Biotecnología, Spain

                Reviewed by: Morten Otto Alexander Sommer, Technical University of Denmark, Denmark; Jose L. Martinez, Centro Nacional de Biotecnología, Spain

                *Correspondence: Rustam I. Aminov, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, UK. e-mail: r.aminov@ 123456abdn.ac.uk

                This article was submitted to Frontiers in Antimicrobials, Resistance and Chemotherapy, a specialty of Frontiers in Microbiology.

                Article
                10.3389/fmicb.2010.00134
                3109405
                21687759
                Copyright © 2010 Aminov.

                This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

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                Figures: 0, Tables: 0, Equations: 0, References: 77, Pages: 7, Words: 7327
                Categories
                Microbiology
                Review Article

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