title: Antibacterial efficacy of inhaled squalamine in a rat model of chronic Pseudomonas aeruginosa pneumonia.
abstract: OBJECTIVE
  Squalamine is a steroid extracted from sharks with proven in vitro antibacterial activity. We assessed its efficacy in reducing the lung bacterial load and histological lesions when given via inhalation in a rat model of chronic Pseudomonas aeruginosa pneumonia.
  
  
  METHODS
  Sprague-Dawley rats were inoculated by tracheal intubation with 150 μL of a solution containing 10(8) cfu/mL of agar bead-embedded P. aeruginosa strain PAO1. MICs of squalamine and colistin for this strain were 2-8 and 0.5-1 mg/L, respectively. Starting the day after infection, the animals were treated twice daily with aerosolized squalamine (3 mg), colistin (160 mg) or 0.9% saline for 6 days. The bacterial load and lung histological lesions were evaluated on the seventh day.
  
  
  RESULTS
  Aerosols of squalamine and colistin resulted in a significant reduction in median (IQR) pulmonary bacterial count compared with saline [10(3) (6 × 10(2)-2 × 10(3)), 10(3) (9 × 10(2)-6 × 10(3)) and 10(5) (9 × 10(4)-2 × 10(5)) cfu/lung, respectively; P < 0.001 for both treated groups versus saline]. The lung weight and the lung histological severity score were significantly lower in both treated groups.
  
  
  CONCLUSIONS
  In a model of chronic P. aeruginosa pneumonia, treatment twice daily with a squalamine aerosol for 6 days leads to a significant reduction in the pulmonary bacterial count and pneumonia lesions with an efficacy comparable to that of colistin.
authors: Aix-Marseille Univ, URMITE CNRS-UMR 6236, 13005 Marseille, France.
authors: Sami
authors: S
authors: Hraiech
authors: Fabienne
authors: F
authors: Brégeon
authors: Jean-Michel
authors: JM
authors: Brunel
authors: Jean-Marc
authors: JM
authors: Rolain
authors: Hubert
authors: H
authors: Lepidi
authors: Véronique
authors: V
authors: Andrieu
authors: Didier
authors: D
authors: Raoult
authors: Laurent
authors: L
authors: Papazian
authors: Antoine
authors: A
authors: Roch
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D058491:Bacterial Load; D002777:Cholestanols / Q000008:administration & dosage / Q000494:pharmacology; D002908:Chronic Disease; D003091:Colistin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D008168:Lung / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002777:Cholestanols; C079655:squalamine; D003091:Colistin