Non-inferiority of colistin compared with standard care for the treatment of ventilator-associated pneumonia

Abstract

This study examined the literature on the treatment of ventilator-associated pneumonia (VAP) using colistin or standard care (SC). Based on this clinical material, a meta-analysis was conducted and a non-inferiority test was performed. Studies were selected for inclusion based on the following criteria: (a) patients with VAP; (b) experimental arm based on intravenous or aerosolized colistin; and (c) control arm based on SC. The meta-analysis employed a fixed-effect model, and the endpoint was the rate of clinical response. No pre-specified non-inferiority threshold for the upper boundary of the 95% confidence interval was adopted; instead, the intention was to perform a retrospective evaluation of whether the threshold suggested by the results was acceptable on clinical grounds. In total, eight controlled studies were included. The pooled risk ratio was 1.019 for colistin compared with SC (95% confidence interval 0.895-1.16); this result corresponds to a non-significant 1.9% increase in cure rate with colistin compared with SC (range +16% to -10.5%). Heterogeneity was minimal (0%). The post-hoc non-inferiority threshold for colistin compared with SC was -10.5% in terms of relative cure rate (pooled risk ratio = 0.895). This margin was considered to be acceptable on clinical grounds. This analysis found that colistin can play a role in the treatment of VAP, particularly when given as a combination of aerosolized and intravenous drug.

Keywords: Aerosol; Colistin; Meta-analysis; Ventilator-associated pneumonia.