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      Considerations for Phage Therapy Against Mycobacterium abscessus

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          Abstract

          There is a global increasing number of Mycobacterium abscessus infections, especially pulmonary infections. Reduced therapeutic options exist against this opportunistic pathogen due to its high intrinsic and acquired levels of antibiotic resistance. Phage therapy is a promising afresh therapy, which uses viruses to lyse bacteria responsible for the infection. Bacteriophages have been recently administered under compassionate use to a 15-year-old patient infected with M. abscessus in combination with antibiotics with excellent results. This mini review highlights different recommendations for future phage administrations such as where to look for new phages, the use of cocktail of mycobacteriophages to broaden phage specificity and to tackle resistance and phage insensitivity due to temperate phages present in bacterial genomes, the combined use of phages and antibiotics to obtain a synergistic effect, the liposomal administration to reach a prolonged effect, intracellular delivery and protection against neutralizing antibodies, and the convenience of using this strategy in patients suffering from cystic fibrosis (CF) since phages are believed to promote immunomodulatory actions and eliminate biofilms.

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          Most cited references57

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          Engineered bacteriophages for treatment of a patient with a disseminated drug resistant Mycobacterium abscessus

          A 15-year-old cystic fibrosis patient with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.
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            Bacteriophage resistance mechanisms.

            Phages are now acknowledged as the most abundant microorganisms on the planet and are also possibly the most diversified. This diversity is mostly driven by their dynamic adaptation when facing selective pressure such as phage resistance mechanisms, which are widespread in bacterial hosts. When infecting bacterial cells, phages face a range of antiviral mechanisms, and they have evolved multiple tactics to avoid, circumvent or subvert these mechanisms in order to thrive in most environments. In this Review, we highlight the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems.
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              Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection.

              Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                18 January 2021
                2020
                : 11
                : 609017
                Affiliations
                Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz , Madrid, Spain
                Author notes

                Edited by: Wladimir Sougakoff, INSERM U1135 Centre d'Immunologie et de Maladies Infectieuses, France

                Reviewed by: Regis Tournebize, INSERM U1135 Centre d'Immunologie et de Maladies Infectieuses, France; Jean Louis Herrmann, Université de Versailles Saint-Quentin-en-Yvelines, France

                *Correspondence: Jaime Esteban, jestebanmoreno@ 123456gmail.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.609017
                7847891
                33537013
                acb41c97-87f9-4d61-9ea7-bc8db2595bf9
                Copyright © 2021 Senhaji-Kacha, Esteban and Garcia-Quintanilla.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 September 2020
                : 24 December 2020
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 59, Pages: 6, Words: 5164
                Funding
                Funded by: Ministerio de Ciencia e Innovación of Spain
                Categories
                Microbiology
                Mini Review

                Microbiology & Virology
                mycobacterium abscessus,non-tuberculous mycobacteria,phage therapy,alternative therapy,antibiotic resistance,bacteriophage

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