Efficacy of colistin/rifampin combination in experimental rat models of sepsis due to a multiresistant Pseudomonas aeruginosa strain*

Abstract

To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis. Prospective, randomized, controlled animal study. Research laboratory in a university hospital. Adult male Wistar rats. Adult male Wistar rats were given a) an intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysaccharide; b) 2 x 10(10) colony-forming units of P. aeruginosa ATCC 27853; and c) 2 x 10(10) colony-forming units of one clinically multiresistant strain of P. aeruginosa. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 10 mg/kg rifampin, 1 mg/kg colistin, and 10 mg/kg rifampin plus 1 mg/kg colistin. Lethality, bacterial growth in blood and peritoneum, and endotoxin and tumor necrosis factor-alpha concentrations in plasma were measured. Colistin exerted a strong antimicrobial activity and achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration compared with control and rifampin-treated groups. Rifampin exhibited no antimicrobial activity with no substantial impact on endotoxin and tumor necrosis factor-alpha plasma concentrations. The combination of colistin and rifampin resulted in a significant reduction in bacterial count compared with colistin monotherapy, whereas no significant difference was found in positive hem cultures and mortality rates between the two groups. Colistin and rifampin might have a role in the therapy of multiresistant P. aeruginosa infection.