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      Using the Chinese herb Scutellaria barbata against extensively drug-resistant Acinetobacter baumannii infections: in vitro and in vivo studies

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          Abstract

          Background

          No animal model studies have been conducted in which the efficacy of herbal compounds has been tested against multidrug-resistant Acinetobacter baumannii infections. Very few antibiotics are available for the treatment of pulmonary infections caused by extensively drug-resistant Acinetobacter baumannii (XDRAB). To find alternative treatments, traditional Chinese herbs were screened for their antimicrobial potential.

          Methods

          The present study screened 30 herbs that are traditionally used in Taiwan and that are commonly prescribed for heat clearing and detoxification. The herbs with antibacterial activities were analysed by disc diffusion assays, time-kill assays and a murine lung infection model.

          Results

          Of the 30 herbs tested, only Scutellaria barbata demonstrated 100% in vitro activity against XDRAB. Furthermore, we compared the antibacterial effect of the S. barbata extract with that of colistin, and the S. barbata extract showed better antibacterial effect. In the XDRAB pneumonia murine model, we compared the antimicrobial effects of the orally administered S. barbata extract (200 mg/kg, every 24 h), the intratracheally administered colistin (75,000 U/kg, every 12 h), and the control group. The bacterial load in the lungs of the treatment group that received the oral S. barbata extract showed a significant decrease in comparison to that in the lungs of the control group. In addition, histopathological examinations also revealed better resolution of perivascular, peribronchial, and alveolar inflammation in the oral S. barbata extract-treated group.

          Conclusions

          Our in vitro and in vivo data from the animal model support the use of S. barbata as an alternate drug to treat XDRAB pulmonary infections. However, detailed animal studies and clinical trials are necessary to establish the clinical utility of S. barbata in treating XDRAB pulmonary infections.

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          Most cited references31

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          Bacteriophage host range and bacterial resistance.

          Host range describes the breadth of organisms a parasite is capable of infecting, with limits on host range stemming from parasite, host, or environmental characteristics. Parasites can adapt to overcome host or environmental limitations, while hosts can adapt to control the negative impact of parasites. We consider these adaptations as they occur among bacteriophages (phages) and their bacterial hosts, since they are significant to phage use as antibacterials (phage therapy) or to protection of industrial ferments from phage attack. Initially, we address how phage host range can (and should) be defined plus summarize claims of host ranges spanning multiple bacterial genera. Subsequently, we review bacterial mechanisms of phage resistance. These include adsorption resistance, which results in reduced interaction between phage and bacterium; what we describe as "restriction," where bacteria live but phages die; and abortive infections, where both phage and bacterium die. Adsorption resistance includes loss of phage receptor molecules on hosts as well as physical barriers hiding receptor molecules (e.g., capsules). Restriction mechanisms include phage-genome uptake blocks, superinfection immunity, restriction modification, and CRISPR, all of which function postphage adsorption but prior to terminal phage takeover of host metabolism. Standard laboratory selection methods, involving exposure of planktonic bacteria to high phage densities, tend to directly select for these prehost-takeover resistance mechanisms. Alternatively, resistance mechanisms that do not prevent bacterium death are less readily artificially selected. Contrasting especially bacteria mutation to adsorption resistance, these latter mechanisms likely are an underappreciated avenue of bacterial resistance to phage attack. Copyright 2010 Elsevier Inc. All rights reserved.
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            Current control and treatment of multidrug-resistant Acinetobacter baumannii infections.

            Institutional outbreaks caused by Acinetobacter baumannii strains that have acquired multiple mechanisms of antimicrobial drug resistance constitute a growing public-health problem. Because of complex epidemiology, infection control of these outbreaks is difficult to attain. Identification of potential common sources of an outbreak, through surveillance cultures and epidemiological typing studies, can aid in the implementation of specific control measures. Adherence to a series of infection control methods including strict environmental cleaning, effective sterilisation of reusable medical equipment, attention to proper hand hygiene practices, and use of contact precautions, together with appropriate administrative guidance and support, are required for the containment of an outbreak. Effective antibiotic treatment of A baumannii infections, such as ventilator-associated pneumonia and bloodstream infections, is also of paramount importance. Carbapenems have long been regarded as the agents of choice, but resistance rates have risen substantially in some areas. Sulbactam has been successfully used in the treatment of serious A baumannii infections; however, the activity of this agent against carbapenem-resistant isolates is decreasing. Polymyxins show reliable antimicrobial activity against A baumannii isolates. Available clinical reports, although consisting of small-sized studies, support their effectiveness and mitigate previous concerns for toxicity. Minocycline, and particularly its derivative, tigecycline, have shown high antimicrobial activity against A baumannii, though relevant clinical evidence is still scarce. Several issues regarding the optimum therapeutic choices for multidrug-resistant A baumannii infections need to be clarified by future research.
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              Immunomodulatory and antimicrobial effects of some traditional chinese medicinal herbs: a review.

              The current practice of ingesting phytochemicals to support the immune system or to fight infections is based on centuries-old tradition. We review reports on seven Chinese herbs, (Aloe vera Mill. (Aloaceae), Angelica species (Umbelliferae), Astragalus membranaceus Bunge. (Leguminosae), Ganoderma lucidum (Fr.) Karst. (Ganodermataceae), Panax ginseng C.A Mey. (Araliaceae), Scutellaria species (Lamiaceae) and Zingiber officinale Rosc. (Zingiberaceae) with emphasis to their immunomodulatory and antimicrobial activities. While some of these herbaceous plants have a direct inhibitory effect on microbial organisms, we observe that each plant has at least one compound that selectively modulates cells of the immune system. The successful derivation of pure bioactive compounds from Ganoderma lucidum, ginseng and Zingiber officinale supports the traditional practice of using these plants to stimulate the immune system. As many modern drugs are often patterned after phytochemicals, studying the influence of each compound on immune cells as well as microbes can provide useful insights to the development of potentially useful new pharmacological agents.
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                Author and article information

                Contributors
                chhung@isu.edu.tw
                886 6 2353535 , jiunlingwang@gmail.com
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                20 March 2018
                20 March 2018
                2018
                : 18
                : 96
                Affiliations
                [1 ]ISNI 0000 0004 0637 1806, GRID grid.411447.3, School of Chinese Medicine for Post-Baccalaureates, Chinese Medicine Department, , I-Shou University and E-DA Hospital, ; Kaoshiung, Taiwan
                [2 ]ISNI 0000 0004 0637 1806, GRID grid.411447.3, Department of Medical Research, , E-DA Hospital and School of Medicine, I-Shou University, ; Kaoshiung, Taiwan
                [3 ]Department of Pathology, Taipei Medical University Hospital and , School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan
                [4 ]ISNI 0000 0004 0637 1806, GRID grid.411447.3, Department of Chemical Engineering, and Institute of Biotechnology, , I-Shou University, ; Kaoshiung, Taiwan
                [5 ]ISNI 0000 0004 0532 3255, GRID grid.64523.36, Department of Internal Medicine, , National Cheng Kung University Hospital and College of Medicine,National Cheng Kung University, ; No. 138, Sheng Li Road, Tainan, 70403 Taiwan
                Author information
                http://orcid.org/0000-0002-9465-8692
                Article
                2151
                10.1186/s12906-018-2151-7
                5859712
                29554903
                7e42f368-97bf-48c8-9792-3d12d39e497c
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 July 2017
                : 1 March 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004663, Ministry of Science and Technology, Taiwan;
                Award ID: 103-2314-B-214-001
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004738, E-Da Hospital;
                Award ID: , EDAHP105009 EDAHP104050 EDAHP103016
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Complementary & Alternative medicine
                multidrug-resistant acinetobacter baumannii,scutellaria barbata,disc diffusion method,time-kill curve,animal model

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