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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
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    • "The perceived lack of return on investment in the field of antibacterial research has led industry to focus more on markets of chronic diseases, rather than acute infectious diseases. It seems that antibiotics are not perceived as being essential to health; however , they have saved millions of lives since these drugs were introduced in the early 1930s, permitting individuals to live for many years after infection [11]. As stated by Bush et al. [9], in the battle against antimicrobial resistance, natural products appear as a vast reservoir of bioactive compounds available in nature that merit to be exploited. "
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    ABSTRACT: Coated pellets and mini-tablets were prepared containing a new broad spectrum antibacterial agent: CIN-102, a well-defined, synergistic blend of trans-cinnamaldehyde, trans-2-methoxycinnamaldehyde, cinnamyl acetate, linalool, β-caryophyllene, cineol and benzyl benzoate. The aim was to provide a new treatment method for colitis, especially for Inflammatory Bowel Disease (IBD) patients. Since the simple oral gavage of CIN-102 was not able to reduce the pathogenic bacteria involved in colitis (rat model), the drug was incorporated into multiparticulates. The idea was to minimize undesired drug release in the upper gastro intestinal tract and to control CIN-102 release in the colon, in order to optimize the resulting antibiotic concentration at the site of action. A particular challenge was the fact that CIN-102 is a volatile hydrophobic liquid. Pellet cores were prepared by extrusion-spheronization and coated with polymer blends, which are sensitive to colonic bacterial enzymes. Mini-tablets were prepared by direct compression. The release of the main compound of CIN-102 (cinnamaldehyde, 86.7% w/w) was monitored in vitro. Optimized coated pellets and mini-tablets were also tested in vivo: in seven-week-old, male mice suffering from dextran sodium sulfate induced colitis. Importantly, both types of multiparticulates were able: (i)to significantly reduce the number of luminal and mucosal enterobacteria in the mice (the levels of which are increased in the disease state), and (ii)to improve the clinical course of the intestinal inflammation (decrease in the percentages of mice with bloody stools and diarrhea). Thus, the proposed coated pellets and matrix mini-tablets allowing for controlled CIN-102 release show a promising potential for new treatment methods of colitis. Copyright © 2015. Published by Elsevier B.V.
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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.
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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.
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