title: Efficacy of colistin/rifampin combination in experimental rat models of sepsis due to a multiresistant Pseudomonas aeruginosa strain.
abstract: OBJECTIVE
  To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis.
  
  
  METHODS
  Prospective, randomized, controlled animal study.
  
  
  METHODS
  Research laboratory in a university hospital.
  
  
  METHODS
  Adult male Wistar rats.
  
  
  METHODS
  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.
  
  
  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.
authors: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors: Oscar
authors: O
authors: Cirioni
authors: Roberto
authors: R
authors: Ghiselli
authors: Fiorenza
authors: F
authors: Orlando
authors: Carmela
authors: C
authors: Silvestri
authors: Federico
authors: F
authors: Mocchegiani
authors: Marco
authors: M
authors: Rocchi
authors: Leonardo
authors: L
authors: Chiodi
authors: Alessandra
authors: A
authors: Abbruzzetti
authors: Vittorio
authors: V
authors: Saba
authors: Giorgio
authors: G
authors: Scalise
authors: Andrea
authors: A
authors: Giacometti
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002478:Cells, Cultured; D003091:Colistin / Q000008:administration & dosage* / Q000494:pharmacology; D015169:Colony Count, Microbial; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage* / Q000494:pharmacology; D012772:Shock, Septic / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D012293:Rifampin; D003091:Colistin