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      Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence

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          Abstract

          Background: Shigella remains the primary cause of diarrhoea in paediatric patients worldwide and accounts for up to 40,000 deaths per year. Current guidelines for the treatment of shigellosis are based on data which are over a decade old. In an era of increasing antimicrobial resistance, an updated review of the appropriate empirical therapy for shigellosis in children is necessary, taking into account susceptibility patterns, cost and the risk of adverse events.

          Methods: A systematic review of the current published literature on the treatment of shigella dysentery was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

          Results: The initial search produced 131 results, of which nine studies met the inclusion criteria. The quality of the studies was assessed as per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. International guidelines were also reviewed. There is a lack of current research regarding the clinical treatment of shigellosis in paediatric and adult patients, despite rising antimicrobial resistance worldwide. In particular, there is a lack of studies assessing the non-susceptibility of community-acquired strains, with almost all published research pertaining to microbiological data from hospital-based settings.

          Discussion: Current WHO guidelines support the use of fluoroquinolones (first-line), β-lactams (second-line) and cephalosporins (second-line) which accords with currently available evidence and other international guidelines, and there is no strong evidence for changing this guidance. Azithromycin is appropriate as a second-line therapy in regions where the rate of non-susceptibility of ciprofloxacin is known to be high, and research suggests that, from a cardiac point of view, azithromycin is safer than other macrolide antibiotics. Cefixime is also a reasonable alternative, although its use must be weighed against the risk of dissemination of extended-spectrum β-lactamase-producing organisms.

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          Most cited references50

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          GRADE guidelines: 3. Rating the quality of evidence.

          This article introduces the approach of GRADE to rating quality of evidence. GRADE specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies. In the context of a systematic review, quality reflects our confidence that the estimates of the effect are correct. In the context of recommendations, quality reflects our confidence that the effect estimates are adequate to support a particular recommendation. Randomized trials begin as high-quality evidence, observational studies as low quality. "Quality" as used in GRADE means more than risk of bias and so may also be compromised by imprecision, inconsistency, indirectness of study results, and publication bias. In addition, several factors can increase our confidence in an estimate of effect. GRADE provides a systematic approach for considering and reporting each of these factors. GRADE separates the process of assessing quality of evidence from the process of making recommendations. Judgments about the strength of a recommendation depend on more than just the quality of evidence. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study.

            Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.
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              Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

              Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.
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                Author and article information

                Journal
                Paediatr Int Child Health
                Paediatr Int Child Health
                YPCH
                ypch20
                Paediatrics and International Child Health
                Taylor & Francis
                2046-9047
                2046-9055
                2018
                23 May 2018
                : 38
                : Suppl 1 , Antibiotics for bacterial infections in children
                : S50-S65
                Affiliations
                [a ] Nuffield Department of Clinical Medicine, The University of Oxford , Oxford, UK
                [b ] Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme , Kilifi, Kenya
                [c ] The Childhood Acute Illness and Nutrition Network (CHAIN) , Kilifi, Kenya
                [d ] Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, The University of Oxford , Oxford, UK
                Author notes
                [* ]Corresponding author. Email: phoebe.williams@ 123456univ.ox.ac.uk
                Author information
                http://orcid.org/0000-0003-2250-0594
                http://orcid.org/0000-0002-1236-849X
                Article
                1409454
                10.1080/20469047.2017.1409454
                6021764
                29790845
                06cd69d0-7b27-4c9c-8c9a-756edef33159
                © 2018 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
                : 15 September 2017
                : 04 November 2017
                Page count
                Figures: 1, Tables: 6, Equations: 0, References: 60, Pages: 16
                Funding
                Funded by: Childhood Acute Illness and Nutrition Network
                Award ID: BMGF
                Award ID: OPP1131320
                Funded by: FLACSAM
                Award ID: MRC/DfID/Wellcome Trust Joint Global Health Trials
                Award ID: MR/M007367/1
                Funded by: World Health Organization 10.13039/100004423
                Award ID: N/A
                Categories
                Reviews

                Pediatrics
                dysentery,shigellosis,shigella,antibiotics,antimicrobial resistance,treatment guidelines
                Pediatrics
                dysentery, shigellosis, shigella, antibiotics, antimicrobial resistance, treatment guidelines

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