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.
Keywords
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Article Info
Publication History
Published online: June 06, 2016
Accepted:
May 24,
2016
Received in revised form:
May 23,
2016
Received:
March 7,
2016
Identification
Copyright
© 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
