Hughes, J. M. Preserving the lifesaving power of antimicrobial agents. JAMA 305, 1027-1028

Infectious Diseases Society of America, Arlington, Virginia, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 02/2011; 305(10):1027-8. DOI: 10.1001/jama.2011.279
Source: PubMed
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Available from: James M Hughes,
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    • "In Gram-negative bacteria like Salmonella enterica subspecies I, serovar Typhimurium drug susceptibility is associated with multidrug efflux systems and an outer membrane (OM) barrier [5]. Furthermore, the antibiotic pipeline has become extremely dry [6]. Therefore, development of novel effective antibacterial drugs targeting previously unexploited bacterial enzymes is essential to fight the drug-resistant bacteria in future [7]. "
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    ABSTRACT: The Mur enzymes of the peptidoglycan biosynthesis pathway constitute ideal targets for the design of new classes of antimicrobial inhibitors in Gram-negative bacteria. We built a homology model of MurD of S. Typhimurium LT2 using MODELLER (9v12) software. The homology model was subjected to energy minimization by Molecular Dynamics (MD) simulation study with GROMACS software for a simulation time of 20 ns in water environment. The model was subjected for virtual screening study from the Zinc Database using Dockblaster software. Inhibition assay for the best inhibitor, 3-(amino methyl)-n-(4-methoxyphenyl) aniline by flow cytometric analysis revealed the effective inhibition of peptidoglycan biosynthesis. Results from this study provide new insights for the molecular understanding and development of new antibacterial drugs against the pathogen. Copyright © 2015. Published by Elsevier Inc.
    Journal of pharmacological and toxicological methods 04/2015; 73. DOI:10.1016/j.vascn.2015.03.005 · 2.39 Impact Factor
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    • "Among the most important medicines ever discovered, antimicrobial agents have saved millions of lives and improved the outcomes for countless patients since these drugs were introduced in the early 1930s [1]. However, the emergence and spread of resistance in multiple microorganisms have rendered the management of many infectious diseases more difficult [2]. "
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    ABSTRACT: The World Health Organization (WHO) selected antimicrobial resistance (AMR) as the theme for World Health Day 2011. The slogan was "Combat Drug Resistance -- No action today, no cure tomorrow" A six-point policy package was launched as a core product for World Health Day. It aimed to stimulate extensive and coherent action to overcome the many challenges presented by antimicrobial resistance. As a preparation for World Health Day, interviews were conducted with a series of key informants, mainly senior government staff, to assess their awareness of the topic and the interventions proposed in the policy package. Since the key informant interview methodology was used with a small number of interviewees, it may be difficult to demonstrate the validity of the findings. Key informants from twelve out of fifteen countries responded, which included Fiji (n = 5), Kiribati (n = 1), Lao PDR (n = 2), Malaysia (n = 6), Micronesia (n = 3), Mongolia (n = 5), the Philippines (n = 5), Vietnam (n = 6), Vanuatu (n = 1), Solomon Islands (n = 3), Cambodia (n = 5) and Brunei (n = 1). There was a total of forty-three respondents (n = 43). AMR was widely recognized as a problem. Lack of a coherent, comprehensive and national plan or strategy was noted. Surveillance was often seen as weak and fragmented even where presented. Laboratory capacity was felt to be insufficient across all countries interviewed. The majority of respondents stressed the need for national and local plans to combat AMR including reliable estimates of the financial cost of combating and managing AMR, the need for legislation to control inappropriate use of antimicrobials in food animals and more serious efforts to promote Standard Treatment Guidelines (STGs) and Rational Prescription. Also, importance was highlighted of the need to include infection prevention and control (IPC) as a part of accreditation and registration of health institutions and programs to promote IPC to the general population. A coalition of interested parties at the local, national and international levels need to generate and sustain the political will to organize a more comprehensive, sustainable, and coherent approach to AMR.
    Globalization and Health 07/2013; 9(1):34. DOI:10.1186/1744-8603-9-34 · 2.25 Impact Factor
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    • "Second, the antibiotic-pipeline has become extremely dry in the last 10-15 years (Shriram et. al., 2008; Gootz, 2010; Hughes, 2011; Carlet et. al., 2012). "
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    ABSTRACT: This study was in continuation of our earlier efforts in identifying phyto-derived agents as potential source for curing plasmid-mediated antibiotic resistance. Aqueous and methanol extracts of Alpinia galanga rhizomes were tried against multiple drug resistant (MDR) clinical isolates of Enterococcus faecalis, Staphylococcus aureus, Salmonella typhi, Shigella sonnei, as well as reference plasmid-harboring strains of Escherichia coli (RP4) and Bacillus subtilis (pUB110). Methanol extract exhibited bactericidal activities against reference plasmid harboring strains E. coli, B. subtilis and clinical isolate S. sonnei at 1200, 800 and 1200 μg/ml, respectively. Aqueous extract could not inhibit the growth of any pathogenic strain up to 1200 μg/ml concentrations. However, both the extracts were highly effective in curing plasmid-encoded antibiotic resistance in bacterial strains of clinical origin. Methanol extract showed plasmid curing at a much lower (400 μg/ml) concentration as compared to the aqueous extract (1200 μg/ml) and against wider range of clinical isolates. Methanol extracts showed a very high (98%) plasmid curing efficiency against S. typhi, followed by 50, 42 and 22 percent curing efficiencies against E. faecalis, S. aureus and S. sonnei respectively. Aqueous extract also showed noticeable antibiotic resistance reversal activities against R-plasmid harboring strains of clinical origin- E. faecalis, S. aureus and S. typhi with curing efficiencies of 72%, 70% and 12% respectively. The elimination of R-plasmids reversed the multiple antibiotic resistances in cured derivatives making them sensitive to low concentrations of antibiotics. Both the extracts seem to be potential source for controlling the development and spread of plasmid-borne multiple antibiotic resistance.
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