Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis.
Clin Microbiol Infect. 2016 Jun 6;
Authors: Paul M, Dickstein Y, Raz-Pasteur A
Abstract
BACKGROUND: Antibiotic de-escalation is an appealing strategy in antibiotic stewardship programs. We aimed to assess its safety and effects.
METHODS: Systematic review and meta-analysis. We included randomized controlled trials (RCTs) and observational studies assessing adults with bacteremia, microbiologically-documented pneumonia or severe sepsis, comparing between antibiotic de-escalation vs. no de-escalation. De-escalation was defined as changing an initially covering antibiotic regimen to a narrower spectrum regimen based on antibiotic susceptibility testing (AST) results within 96 hrs. 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 odds ratios (OR) with 95% confidence intervals were pooled in random-effects meta-analyses.
RESULTS: 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 (0.39-0.73), 19 studies, moderate heterogeneity. In the adjusted analysis there was no significant difference in mortality, adjusted OR 0.83 (0.59-1.16), 11 studies, moderate heterogeneity and the RCTs showed non-significant increased mortality with de-escalation, OR 1.73 (0.97-3.06), 3 trials, no heterogeneity. There was a significant unadjusted association between de-escalation and survival in bacteremia/ severe sepsis (OR 0.45, 0.30-0.67) and ventilator-associated pneumonia (VAP, OR 0.49, 0.26-0.95), but not with other pneumonia (OR 0.97, 0.45-2.12). Only two studies reported on emergence of resistance with inconsistent findings.
CONCLUSIONS: Observational studies suggest lower mortality with AST-based de-escalation for bacteremia, severe sepsis and VAP that was not demonstrated in RCTs.
PMID: 27283148 [PubMed - as supplied by publisher]