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      Synthesis and evaluation of polymeric micelle containing piperacillin/tazobactam for enhanced antibacterial activity

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          Abstract

          Infections caused by multidrug-resistant bacteria such as P. aeruginosa are important therapeutic complications. Piperacillin/Tazobactam is considered a safe antimicrobial agent. But we should not ignore the prevalence of resistant strains to this drug. In this work, a new polymeric micelle composed of Piperacillin/Tazobactam-loaded Poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PLGA-PEG) was developed to improve the antimicrobial performance of P/T. The SEM and TEM studies of PLGA-PEG micelle showed, semi-spherical morphology with a mean diameter of below 30 nm. Zeta potential results indicated that the surface charge of PLGA-PEG micelle was −2.98 mV, while after encapsulation of P/T, the surface charge decreases to −4.13 mV. Clinical strains of P. aeruginosa were isolated and their resistance pattern against different antibiotics was evaluated. The MIC of free and P/T -Loaded PLGA-PEG micelles was determined. Also, the effect of free or P/T micelle against minimal biofilm eradication concentration and motility inhibition was evaluated. The bacterial isolates were resistant to most common antibiotics. The MIC of the free drug form and micelle form ranged from 4 to 512 µg/ml and 2 to 256 µg/ml, respectively. Generally, micelle showed more effective antibiofilm activities, inhibition of bacterial motility and reducing the MIC than that free drug form.

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          Quantification of biofilm in microtiter plates: overview of testing conditions and practical recommendations for assessment of biofilm production by staphylococci.

          The details of all steps involved in the quantification of biofilm formation in microtiter plates are described. The presented protocol incorporates information on assessment of biofilm production by staphylococci, gained both by direct experience as well as by analysis of methods for assaying biofilm production. The obtained results should simplify quantification of biofilm formation in microtiter plates, and make it more reliable and comparable among different laboratories.
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            How to manage Pseudomonas aeruginosa infections

            Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. Diverse strategies range from killing (new antibiotics) to disarming (antivirulence) the pathogen. In this review, selected aspects of P. aeruginosa antimicrobial resistance and infection management will be addressed. Many studies have been performed to evaluate the risk factors for resistance and the potential consequences on mortality and attributable mortality. The review also looks at the mechanisms associated with resistance – P. aeruginosa is a pathogen presenting a large genome, and it can develop a large number of factors associated with antibiotic resistance involving almost all classes of antibiotics. Clinical approaches to patients with bacteremia, ventilator-associated pneumonia, urinary tract infections and skin soft tissue infections are discussed. Antibiotic combinations are reviewed as well as an analysis of pharmacokinetic and pharmacodynamic parameters to optimize P. aeruginosa treatment. Limitations of current therapies, the potential for alternative drugs and new therapeutic options are also discussed.
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              The role of motility as a virulence factor in bacteria.

              Many bacteria that cause diseases of humans, animals and plants use flagella to move. This review summarises recent studies that have analysed the role of motility and chemotaxis in the host-parasite relationship of pathogenic bacteria. These studies have shown that for many pathogens, motility is essential in some phases of their life cycle and that virulence and motility are often intimately linked by complex regulatory networks. Possibilities to exploit bacterial motility as a specific therapeutic antibacterial target to cure or prevent disease are discussed.
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                Author and article information

                Journal
                Drug Deliv
                Drug Deliv
                IDRD
                idrd20
                Drug Delivery
                Taylor & Francis
                1071-7544
                1521-0464
                2019
                4 December 2019
                : 26
                : 1
                : 1292-1299
                Affiliations
                [a ]Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences , Tabriz, Iran;
                [b ]Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz, Iran;
                [c ]Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences , Tabriz, Iran
                Author notes

                Supplemental data for this article can be accessed here .

                Abolfazl Akbarzadeh a.akbarzadeh2020@ 123456gmail.com Faculty of Advanced Medical, Tabriz University of Medical Sciences , Tabriz, Iran
                Article
                1693708
                10.1080/10717544.2019.1693708
                6896493
                31797692
                505da646-75d5-41ac-ac02-a92f4792fe62
                © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 October 2019
                : 05 November 2019
                : 11 November 2019
                Page count
                Figures: 6, Tables: 2, Pages: 8, Words: 5215
                Funding
                Funded by: Iran National Science Foundation (INSF) 10.13039/501100003968
                The study was supported by a Grant (96003523) from the Iran National Science Foundation (INSF).
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                p. aeruginosa,piperacillin/tazobactam,polymeric micelle,antibiotic resistance

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