Colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia (Magic Bullet study): an investigator-driven, open-label, randomized, noninferiority controlled trial.

摘要: Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence carbapenem-resistant gram-negative bacilli (CR-GNB). However, efficacy and safety colistin are not well defined. A multicenter prospective randomized trial conducted 32 European centers compared (4.5 million unit loading dose followed by maintenance 3 units every 8 h) versus meropenem (2 g 8 h), both combination levofloxacin (500 mg 12 h) for 7–14 days patients late VAP. Between May 2012 October 2015, 232 were randomly assigned to 2 groups. The primary endpoint was mortality at 28 days after randomization microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical microbiological cure, renal function end treatment, serious adverse events. study interrupted interim analysis due excessive nephrotoxicity group; therefore, sample size achieved. total 157 (67.7%) mMITT population, 36 whom (22.9%) had VAP caused CR-GNB. In no significant difference between group (19/82, 23.2%) (19/75, 25.3%) observed, risk − 2.16 (− 15.59 11.26, p = 0.377); noninferiority demonstrated early termination limited number infected pathogens. plus increased incidence failure (40/120, 33.3%, 21/112, 18.8%; p = 0.012) replacement therapy (11/120, 9.1%, 2/112, 1.8%; p = 0.015). This did demonstrate meropenem, combined levofloxacin, terms but greater colistin. These findings do support use termination. ClinicalTrials.gov, NCT01292031. Registered 9 February 2011.