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      Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives

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          Abstract

          The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.

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          Most cited references120

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          European consensus conference on faecal microbiota transplantation in clinical practice

          Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
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            The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation.

            Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT. © 2014 by The American Society of Hematology.
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              The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs.

              There is an association between the development of antimicrobial resistance in Staphylococcus aureus, enterococci, and gram-negative bacilli and increases in mortality, morbidity, length of hospitalization, and cost of health care. For many patients, inadequate or delayed therapy and severe underlying disease are primarily responsible for the adverse outcomes of infections caused by antimicrobial-resistant organisms. Patients with infections due to antimicrobial-resistant organisms have higher costs (approximately 6,000-30,000 dollars) than do patients with infections due to antimicrobial-susceptible organisms; the difference in cost is even greater when patients infected with antimicrobial-resistant organisms are compared with patients without infection. Strategies to prevent nosocomial emergence and spread of antimicrobial-resistant organisms are essential.
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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
                25 July 2019
                2019
                : 10
                : 1704
                Affiliations
                [1] 1Division of Immunology and Infectious Diseases, University-Hospital Pediatric Department, Bambino Gesù Children’s Hospital , IRCSS, Rome, Italy
                [2] 2Human Microbiome Unit, Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy
                [3] 3Human Microbiome Unit and Parasitology Unit, Bambino Gesù Children’s Hospital , IRCCS, Rome, Italy
                Author notes

                Edited by: Peter Mullany, University College London, United Kingdom

                Reviewed by: Markus M. Heimesaat, Charité Medical University of Berlin, Germany; Srishti Saha, Mayo Clinic, United States

                *Correspondence: Lorenza Putignani, lorenza.putignani@ 123456opbg.net

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

                Article
                10.3389/fmicb.2019.01704
                6671974
                31402904
                ce00f9e9-1e8d-4803-ac3b-0e6a9f5b1034
                Copyright © 2019 Gargiullo, Del Chierico, D’Argenio and Putignani.

                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
                : 01 April 2019
                : 10 July 2019
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 144, Pages: 16, Words: 0
                Funding
                Funded by: Ministero della Salute 10.13039/501100003196
                Categories
                Microbiology
                Review

                Microbiology & Virology
                antimicrobial resistance,clinical and laboratory advanced stewardship,microbiota profiling,fecal microbiota transplantation (fmt),antimicrobial stewardship (ams),antimicrobial stewardship program (asp),multidrug resistance (mdr) bacteria,microbiota modulation strategies

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