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

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.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…This benefit is uncertain, though, because another meta-analysis of randomized controlled studies of deescalation failed to demonstrate a similar survival advantage [219]. Meta-analyses also suggest that procalcitonin can also be used to assist in differentiating infectious and noninfectious conditions at presentation [211,214,216].…”

Rapid syndromic molecular testing in pneumonia: The current landscape and future potential

“…High quality data is lacking but observational data and limited interventional data suggests this is safe [52][53][54] . A systematic review by Paul et al 55 included studies with CAP, HAP, VAP and Blood stream infection. The reviewers found no association between de-escalation and survival with pneumonia (OR 0.97, 95% CI 0.45-2.12).…”

A Practical Approach to Clinical Antibiotic Stewardship in the ICU Patient with Severe Infection

“…95 Observational data have demonstrated the safety of de-escalation, even in severe infections such as bloodstream infections, VAP, or in patients with neutropenia or presenting with septic shock. 93,[96][97][98][99][100][101] A landmark prospective noninferiority trial could not confirm a worse outcome in patients with a de-escalated antibiotic therapy. 102 While no definitive conclusion about mortality could be made, a 2016 systematic review did associate de-escalation to a better patient outcome.…”