The Short versus Long antibiotic course for pleural Infection Management (SLIM) randomised controlled open label trial

Abstract Background and objective: The optimal length of antibiotic treatment for pleural infection in adults is not known but a minimum of four weeks is typically recommended. 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 the incidence of antibiotic-related adverse reactions.Results: Between November 2020 and October 2021 50 patients (35 (70%) males, mean age 46+13.7 years), 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 4 (16.7%) patients in the short course group and 3 (12.5%) patients in the long course group. In the intention-to-treat analysis the odds ratio for treatment failure in the long course group was 0.714 (95% CI 0.142-3.600, p=0.683). The median duration of antibiotic treatment in the short course group was 20.5 [18-22.5] days compared to 34.5 [32-38] days in the long course group (p <0.001). There were no statistically significant differences in the other outcomes.Conclusion: In medically treated adult patients with pleural infection who are stabilised within 14 days of admission and who are not at high risk of mortality a long course of antimicrobial therapy is potentially not superior to a shorter course in terms of risk of treatment failure. These findings need confirmation in a larger multi-centre trial. Trial protocol registration: NCT04615286 (Clinicaltrials.gov), registration date 4th November 2020.