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      Antimicrobial Polymers: The Potential Replacement of Existing Antibiotics?

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          Abstract

          Antimicrobial resistance is now considered a major global challenge; compromising medical advancements and our ability to treat infectious disease. Increased antimicrobial resistance has resulted in increased morbidity and mortality due to infectious diseases worldwide. The lack of discovery of novel compounds from natural products or new classes of antimicrobials, encouraged us to recycle discontinued antimicrobials that were previously removed from routine use due to their toxicity, e.g., colistin. Since the discovery of new classes of compounds is extremely expensive and has very little success, one strategy to overcome this issue could be the application of synthetic compounds that possess antimicrobial activities. Polymers with innate antimicrobial properties or that have the ability to be conjugated with other antimicrobial compounds create the possibility for replacement of antimicrobials either for the direct application as medicine or implanted on medical devices to control infection. Here, we provide the latest update on research related to antimicrobial polymers in the context of ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. We summarise polymer subgroups: compounds containing natural peptides, halogens, phosphor and sulfo derivatives and phenol and benzoic derivatives, organometalic polymers, metal nanoparticles incorporated into polymeric carriers, dendrimers and polymer-based guanidine. We intend to enhance understanding in the field and promote further work on the development of polymer based antimicrobial compounds.

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          Most cited references156

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          Silver nanoparticles as a new generation of antimicrobials.

          Silver has been in use since time immemorial in the form of metallic silver, silver nitrate, silver sulfadiazine for the treatment of burns, wounds and several bacterial infections. But due to the emergence of several antibiotics the use of these silver compounds has been declined remarkably. Nanotechnology is gaining tremendous impetus in the present century due to its capability of modulating metals into their nanosize, which drastically changes the chemical, physical and optical properties of metals. Metallic silver in the form of silver nanoparticles has made a remarkable comeback as a potential antimicrobial agent. The use of silver nanoparticles is also important, as several pathogenic bacteria have developed resistance against various antibiotics. Hence, silver nanoparticles have emerged up with diverse medical applications ranging from silver based dressings, silver coated medicinal devices, such as nanogels, nanolotions, etc.
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            Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America.

            The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
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              Strain specificity in antimicrobial activity of silver and copper nanoparticles.

              The antimicrobial properties of silver and copper nanoparticles were investigated using Escherichia coli (four strains), Bacillus subtilis and Staphylococcus aureus (three strains). The average sizes of the silver and copper nanoparticles were 3 nm and 9 nm, respectively, as determined through transmission electron microscopy. Energy-dispersive X-ray spectra of silver and copper nanoparticles revealed that while silver was in its pure form, an oxide layer existed on the copper nanoparticles. The bactericidal effect of silver and copper nanoparticles were compared based on diameter of inhibition zone in disk diffusion tests and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of nanoparticles dispersed in batch cultures. Bacterial sensitivity to nanoparticles was found to vary depending on the microbial species. Disk diffusion studies with E. coli and S. aureus revealed greater effectiveness of the silver nanoparticles compared to the copper nanoparticles. B. subtilis depicted the highest sensitivity to nanoparticles compared to the other strains and was more adversely affected by the copper nanoparticles. Good correlation was observed between MIC and MBC (r2=0.98) measured in liquid cultures. For copper nanoparticles a good negative correlation was observed between the inhibition zone observed in disk diffusion test and MIC/MBC determined based on liquid cultures with the various strains (r2=-0.75). Although strain-specific variation in MIC/MBC was negligible for S. aureus, some strain-specific variation was observed for E. coli.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                04 June 2019
                June 2019
                : 20
                : 11
                : 2747
                Affiliations
                [1 ]Faculty of Veterinary Medicine, Locked bag 36, Universiti Malaysia Kelantan, Pengkalan Chepa 16100, Kelantan, Malaysia; li.peng@ 123456umk.edu.my (L.P.T.); ruhil@ 123456umk.ed.my (R.H.H.); shean.cs@ 123456umk.edu.my (S.S.C.)
                [2 ]School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia; wengkinwong@ 123456usm.my
                [3 ]Royal Veterinary College, Pathobiology and Population Sciences, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK; ajgibson@ 123456rvc.ac.uk
                [4 ]UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London NW3 2PF, UK; a.chivu.14@ 123456ucl.ac.uk
                [5 ]Medicines and Healthcare Regulatory Products Agency, 10 South Colonnade, Canary Wharf, London E14 4PU, UK; mfatimagpina@ 123456gmail.com
                Author notes
                Author information
                https://orcid.org/0000-0002-3092-1201
                https://orcid.org/0000-0003-1668-3224
                https://orcid.org/0000-0003-2189-638X
                Article
                ijms-20-02747
                10.3390/ijms20112747
                6600223
                31167476
                d9b34a4f-33c9-48ea-b23e-1606ef84ac9d
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 January 2019
                : 11 April 2019
                Categories
                Review

                Molecular biology
                antimicrobial resistance,antimicrobial polymers,eskape pathogens
                Molecular biology
                antimicrobial resistance, antimicrobial polymers, eskape pathogens

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