Steven K Korang1, Mathias Maagaard1,2, Joshua B Feinberg1, Anders Perner3,4, Christian Gluud1,5,6, Janus C Jakobsen1,6. 1. Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2. Department of Anaesthesiology, Centre for Anaesthesiological Research, Zealand University Hospital, The Zealand Region of Denmark, Koge, Denmark. 3. Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 4. Department of Clinical Medicine, The Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. 5. The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Abstract
BACKGROUND: Sepsis is common, deadly, and a major challenge to treat. Quinolones added to beta-lactam antibiotics are currently recommended as a second-line empiric regimen in sepsis, but the evidence regarding their benefits and harms is unclear. OBJECTIVE: To assess the benefits and harms of adding quinolones to standard care for sepsis. DATA SOURCES: We conducted a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis. We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, and BIOSIS. STUDY SELECTION: Randomized clinical trials assessing the effects of adding any quinolone to standard care for children and adults with sepsis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened studies and extracted data. The certainty of the evidence was assessed by GRADE. RESULTS: We included three trials randomizing 995 adults. All trials were at overall "high risk of bias." All trials compared a quinolone (moxifloxacin, levofloxacin, or ciprofloxacin) and a beta-lactam antibiotic versus the same beta-lactam antibiotic. We found no evidence of an effect of adding quinolones to beta-lactam antibiotics when assessing all-cause mortality (RR 1.07, 95% CI 0.86 to 1.33; 2 trials; 915 participants; very low certainty of evidence) and serious adverse events (RR 1.00, 95% CI 0.67 to 1.50; 977 participants; two trials; very low certainty of evidence). No trials reported on quality of life. CONCLUSIONS: The effects of adding quinolones to beta-lactam antibiotics for the treatment of sepsis were unclear for all outcomes. Additional trial data are warranted to support the recommendation of empirical use of quinolones for sepsis.
BACKGROUND:Sepsis is common, deadly, and a major challenge to treat. Quinolones added to beta-lactam antibiotics are currently recommended as a second-line empiric regimen in sepsis, but the evidence regarding their benefits and harms is unclear. OBJECTIVE: To assess the benefits and harms of adding quinolones to standard care for sepsis. DATA SOURCES: We conducted a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis. We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, and BIOSIS. STUDY SELECTION: Randomized clinical trials assessing the effects of adding any quinolone to standard care for children and adults with sepsis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened studies and extracted data. The certainty of the evidence was assessed by GRADE. RESULTS: We included three trials randomizing 995 adults. All trials were at overall "high risk of bias." All trials compared a quinolone (moxifloxacin, levofloxacin, or ciprofloxacin) and a beta-lactam antibiotic versus the same beta-lactam antibiotic. We found no evidence of an effect of adding quinolones to beta-lactam antibiotics when assessing all-cause mortality (RR 1.07, 95% CI 0.86 to 1.33; 2 trials; 915 participants; very low certainty of evidence) and serious adverse events (RR 1.00, 95% CI 0.67 to 1.50; 977 participants; two trials; very low certainty of evidence). No trials reported on quality of life. CONCLUSIONS: The effects of adding quinolones to beta-lactam antibiotics for the treatment of sepsis were unclear for all outcomes. Additional trial data are warranted to support the recommendation of empirical use of quinolones for sepsis.