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      The Short versus Long Antibiotic Course for Pleural Infection Management (SLIM) randomised controlled open-label trial

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          Abstract

          Introduction

          Based on expert opinion, the length of antibiotic treatment for pleural infection in adults is typically recommended to be a minimum of 4 weeks. This clinical trial aimed to assess whether shorter antibiotic courses lead to more treatment failures than standard longer courses.

          Methods

          In an open-label randomised controlled trial, adult patients with pleural infection who were medically treated and stabilised within 14 days of admission were randomised to either a short antibiotic course (total course 14–21 days) or a long antibiotic course (total course 28–42 days). Patients were excluded if their baseline RAPID score was >4 (high-risk category). The primary outcome was the incidence of treatment failure by 6 weeks post-admission. Secondary outcomes were total length of antibiotic treatment, proportion of patients who resumed normal activity levels within 6 weeks post-admission, time from discharge to resuming normal activity levels and incidence of antibiotic-related adverse reactions.

          Results

          Between September 2020 and October 2021, 50 patients (mean± sd age 46±13.7 years; 35 (70%) males) were recruited to the trial and randomly assigned to the short course group (n=25) or the long course group (n=25), with outcome data available for 24 patients in each study group. Treatment failure occurred in four (16.7%) patients in the short course group and three (12.5%) patients in the long course group. In the intention-to-treat analysis the OR for treatment failure in the long course group was 0.714 (95% CI 0.142–3.600; p=0.683). The median (interquartile range) duration of antibiotic treatment in the short course group was 20.5 (18–22.5) days compared with 34.5 (32–38) days in the long course group (p<0.001). There were no statistically significant differences in the other outcomes.

          Conclusions

          In medically treated adult patients with pleural infection a long course of antimicrobial therapy did not lead to fewer treatment failures compared with a shorter course. These findings need to be confirmed in a larger multicentre trial.

          Abstract

          In medically treated adult patients with pleural infection, a long course of antimicrobial therapy does not lead to fewer treatment failures compared with a shorter course https://bit.ly/3JJHvxn

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          Most cited references24

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          Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

          (2022)
          Summary Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
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            BTS guidelines for the management of community acquired pneumonia in adults: update 2009.

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              Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010.

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                Author and article information

                Journal
                ERJ Open Res
                ERJ Open Res
                ERJOR
                erjor
                ERJ Open Research
                European Respiratory Society
                2312-0541
                March 2023
                11 April 2023
                : 9
                : 2
                : 00635-2022
                Affiliations
                [1 ]Chest Diseases Department, Alexandria University Faculty of Medicine, Alexandria, Egypt
                [2 ]Alexandria University Students Hospitals, Alexandria University, Alexandria, Egypt
                [3 ]Department of Respiratory Medicine, University Hospitals, Plymouth, UK
                Author notes
                Corresponding author: Maged Hassan ( magedhmf@ 123456gmail.com )
                Author information
                https://orcid.org/0000-0002-8768-6548
                https://orcid.org/0000-0002-5235-9221
                Article
                00635-2022
                10.1183/23120541.00635-2022
                10086695
                37057085
                20eda503-39df-4fc0-b006-0d24a74777d1
                Copyright ©The authors 2023

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                : 19 November 2022
                : 31 January 2023
                Categories
                Original Research Articles
                Respiratory Infections
                4

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