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

Objective: To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis. Design: Prospective, randomized, controlled animal study. Setting: Research laboratory in a university hospital. Subjects: Adult male Wistar rats. Interventions: 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. Measurements and Main Results: 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. Conclusions: Colistin and rifampin might have a role in the therapy of multiresistant P. aeruginosa infection.