Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis.
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.
Infectious Diseases Institute, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel. Electronic address: paulm@post.tau.ac.il.
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Paul
Infectious Diseases Institute, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
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Dickstein
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.
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Raz-Pasteur
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015982:Bias; D003141:Communicable Diseases / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D064887:Observational Studies as Topic; D053717:Pneumonia, Ventilator-Associated / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents
Antibiotic treatment; Bias; De-escalation; Empirical antibiotic treatment; Meta-analysis; Observational study; Randomized controlled trial; Susceptibility testing; Systematic review