Antibacterial efficacy of inhaled squalamine in a rat model of chronic Pseudomonas aeruginosa pneumonia

作者:Hraiech Sami; Bregeon Fabienne; Brunel Jean Michel; Rolain Jean Marc; Lepidi Hubert; Andrieu Veronique; Raoult Didier; Papazian Laurent; Roch Antoine*
来源:Journal of Antimicrobial Chemotherapy, 2012, 67(10): 2452-2458.
DOI:10.1093/jac/dks230

摘要

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. %26lt;br%26gt;Sprague-Dawley rats were inoculated by tracheal intubation with 150 L 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 28 and 0.51 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. %26lt;br%26gt;Aerosols of squalamine and colistin resulted in a significant reduction in median (IQR) pulmonary bacterial count compared with saline [10(3) (610(2)210(3)), 10(3) (910(2)610(3)) and 10(5) (910(4)210(5)) cfu/lung, respectively; P0.001 for both treated groups versus saline]. The lung weight and the lung histological severity score were significantly lower in both treated groups. %26lt;br%26gt;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.

  • 出版日期2012-10