Predictors of polymyxin B treatment failure in Gram-negative healthcare-associated infections among critically ill patients

Abstract

Background: With increasing prevalence and spread of multidrug resistant Gram-negative infections, parenteral polymyxins resurged in clinical practice. The primary aim of the study was to determine the predictors of treatment failure and in-hospital mortality among critically ill patients treated with polymyxin B. Methods: Demographic data, underlying diseases, procedures and details on polymyxin B therapy were retrospectively analyzed in a cohort of 84 patients who received intravenous polymyxin B in an intensive care unit from 2010 to 2014. Results: Polymyxin B was used to treat bacteremia (46.4% of cases) and pneumonia (53.6%). Majority of the pathogens isolated were Acinetobacter spp. (96.4%). The mortality rate was 48.8%, of which 82.9% was attributed to polymyxin B treatment failure. The independent predictors of treatment failure were low doses of polymyxin B (p = 0.002), shorter duration of therapy (p = 0.009), not combining with cefoperazone/sulbactam (p = 0.030), female gender (p = 0.004), administered for treatment of bacteremia (p = 0.023) and renal impairment (p = 0.021). Low polymyxin B doses (p = 0.007), not combining with cefoperazone/sulbactam (p = 0.024), female gender (p = 0.048) and renal impairment (p = 0.022) were also significant predictors for in-hospital mortality. Conclusions: To the best of our knowledge, this is the first report on the association of inadequate dose of polymyxin B (<15,000 units/kg/day) with poor outcome in critically ill patients. Besides that, further clinical studies are warranted to evaluate the use of cefoperazone/sulbactam as second antibiotic in the combination therapy. Keywords: Polymyxin B, Critically ill patients, Acinetobacter spp., Treatment failure, Adequate dose, Cefoperazone/sulbactam