Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis

  • Author Footnotes
    3 Authors M. Paul and Y. Dickstein contributed equally to the study.
    M. Paul
    Correspondence
    Corresponding author. M. Paul, Director, Infectious Diseases Institute, Rambam Health Care Campus, Haifa, 3109601, Israel.
    Footnotes
    3 Authors M. Paul and Y. Dickstein contributed equally to the study.
    Affiliations
    Infectious Diseases Institute, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
    Search for articles by this author
  • Author Footnotes
    3 Authors M. Paul and Y. Dickstein contributed equally to the study.
    Y. Dickstein
    Footnotes
    3 Authors M. Paul and Y. Dickstein contributed equally to the study.
    Affiliations
    Infectious Diseases Institute, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
    Search for articles by this author
  • A. Raz-Pasteur
    Affiliations
    Infectious Diseases Institute, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel

    Medicine A, Rambam Health Care Campus, Haifa, Israel
    Search for articles by this author
  • Author Footnotes
    3 Authors M. Paul and Y. Dickstein contributed equally to the study.

      Abstract

      Antibiotic de-escalation is an appealing strategy in antibiotic stewardship programmes. We aimed to assess its safety and effects using a systematic review and meta-analysis. We included randomized controlled trials (RCTs) and observational studies assessing adults with bacteraemia, microbiologically documented pneumonia or severe sepsis, comparing between antibiotic de-escalation and no de-escalation. De-escalation was defined as changing an initially covering antibiotic regimen to a narrower spectrum regimen based on antibiotic susceptibility testing results within 96 hours. The primary outcome was 30-day all-cause mortality. A search of published articles and conference proceedings was last updated in September 2015. Crude and adjusted ORs with 95% CI were pooled in random-effects meta-analyses. Sixteen observational studies and three RCTs were included. Risk of bias related to confounding was high in the observational studies. De-escalation was associated with fewer deaths in the unadjusted analysis (OR 0.53, 95% CI 0.39–0.73), 19 studies, moderate heterogeneity. In the adjusted analysis there was no significant difference in mortality (adjusted OR 0.83, 95% CI 0.59–1.16), 11 studies, moderate heterogeneity and the RCTs showed non-significant increased mortality with de-escalation (OR 1.73, 95% 0.97–3.06), three trials, no heterogeneity. There was a significant unadjusted association between de-escalation and survival in bacteraemia/severe sepsis (OR 0.45, 95% CI 0.30–0.67) and ventilator-associated pneumonia (OR 0.49, 95% CI 0.26–0.95), but not with other pneumonia (OR 0.97, 95% CI 0.45–2.12). Only two studies reported on the emergence of resistance with inconsistent findings. Observational studies suggest lower mortality with antibiotic susceptibility testing-based de-escalation for bacteraemia, severe sepsis and ventilator-associated pneumonia that was not demonstrated in RCTs.

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