OBJECTIVES: 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.
OBJECTIVES: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: Urszula Wnorowska; Katarzyna Niemirowicz; Melissa Myint; Scott L Diamond; Marta Wróblewska; Paul B Savage; Paul A Janmey; Robert Bucki Journal: Antimicrob Agents Chemother Date: 2015-04-13 Impact factor: 5.191
Authors: Paul Zarogoulidis; Ioannis Kioumis; Konstantinos Porpodis; Dionysios Spyratos; Kosmas Tsakiridis; Haidong Huang; Qiang Li; J Francis Turner; Robert Browning; Wolfgang Hohenforst-Schmidt; Konstantinos Zarogoulidis Journal: Drug Des Devel Ther Date: 2013-10-02 Impact factor: 4.162
Authors: Sami Hraiech; Julien Hiblot; John Lafleur; Hubert Lepidi; Laurent Papazian; Jean-Marc Rolain; Didier Raoult; Mikael Elias; Mark W Silby; Janek Bzdrenga; Fabienne Bregeon; Eric Chabriere Journal: PLoS One Date: 2014-10-28 Impact factor: 3.240
Authors: David Collie; John Govan; Steven Wright; Elisabeth Thornton; Peter Tennant; Sionagh Smith; Catherine Doherty; Gerry McLachlan Journal: PLoS One Date: 2013-07-09 Impact factor: 3.240