Preventive antibiotic therapy in acute stroke patients: A systematic review and meta-analysis of individual patient data of randomized controlled trials

Author:

Westendorp Willeke F1ORCID,Vermeij Jan-Dirk2,Smith Craig J34,Kishore Amit K34,Hodsoll John5,Kalra Lalit6,Meisel Andreas7,Chamorro Angel8,Chang Jason J9,Rezaei Yousef10,Amiri-Nikpour Mohammad R11,DeFalco Fabrizio A12,Switzer Jeffrey A13,Blacker David J14,Dijkgraaf Marcel GW15,Nederkoorn Paul J1,van de Beek Diederik1

Affiliation:

1. Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, The Netherlands

2. Department of Neurology, Sint Franciscusziekenhuis, Heusden-Zolder, Belgium

3. Manchester Centre for Clinical Neurosciences, Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, UK

4. Division of Cardiovascular Sciences, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK

5. Biostatistics Department, NIHR Biomedical Research Centre for Mental Health and Institute of Psychiatry, Psychology and Neurosciences, King’s College London, London, UK

6. Clinical Neurosciences, King’s College Hospital NHS Foundation Trust, London, UK

7. Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, NeuroCure Clinical Research Center, Center for Stroke Research Berlin, Berlin, Germany

8. Comprehensive Stroke Center, Department of Neuroscience, Hospital Clinic, University of Barcelona and August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain

9. Department of Critical Care Medicine, MedStar Washington Hospital Center, Washington, DC, USA

10. Heart Valve Disease Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Cardiology, Seyyed-al-Shohada Heart Center, Urmia University of Medical Science, West Azerbaijan, Iran

11. Department of Neurology, Urmia University of Medical Sciences, West Azerbaijan, Iran

12. Neurology Service, Villa dei Fiori Hospital – Acerra, Naples, Italy

13. Department of Neurology, Medical College of Georgia, Augusta, ME, USA

14. Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; School of Medicine and Pharmacology, University of Western Australia

15. Department of Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Abstract

Introduction Infection after stroke is associated with unfavorable outcome. Randomized controlled studies did not show benefit of preventive antibiotics in stroke but lacked power for subgroup analyses. Aim of this study is to assess whether preventive antibiotic therapy after stroke improves functional outcome for specific patient groups in an individual patient data meta-analysis. Patients and methods We searched MEDLINE (1946–7 May 2021), Embase (1947–7 May 2021), CENTRAL (17th September 2021), trial registries, cross-checked references and contacted researchers for randomized controlled trials of preventive antibiotic therapy versus placebo or standard care in ischemic or hemorrhagic stroke patients. Meta-analysis was performed by a one-step and two-step approach. Primary outcome was functional outcome adjusted for age and stroke severity. Secondary outcomes were infections and mortality. Results 4197 patients from nine trials were included. Preventive antibiotic therapy was not associated with a shift in functional outcome (mRS) at 3 months (OR1.13, 95%CI 0.98–1.31) or unfavorable functional outcome (mRS 3–6) (OR0.85, 95%CI 0.60–1.19). Preventive antibiotics did not improve functional outcome in pre-defined subgroups (age, stroke severity, timing and type of antibiotic therapy, pneumonia prediction scores, dysphagia, type of stroke, and type of trial). Preventive antibiotics reduced infections (276/2066 (13.4%) in the preventive antibiotic group vs. 417/2059 (20.3%) in the control group, OR 0.60, 95% CI 0.51–0.71, p < 0.001), but not pneumonia (191/2066 (9.2%) in the preventive antibiotic group vs. 205/2061 (9.9%) in the control group (OR 0.92 (0.75–1.14), p = 0.450). Discussion and conclusion Preventive antibiotic therapy did not benefit any subgroup of patients with acute stroke and currently cannot be recommended.

Funder

National Institute of Health Research

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Clinical Neurology

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