Enhanced Activity of Liposomal Polymyxin B Against Pseudomonas aeruginosa in a Rat Model of Lung Infection

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Authors
  1. Omri, A.
  2. Suntres, Z.E.
  3. Shek, P.N.
Corporate Authors
Defence and Civil Inst of Environmental Medicine, Downsview ONT (CAN)
Abstract
The bactericidal effectiveness of liposomal polymyxin B against Pseudomonas aeruginosa was investigated in an animal model of pulmonary infection. Polymyxin B (PmB) was incorporated into liposomes composed of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (Chol) (2:1). Lung infection was induced in rats following intratracheal instillation of 107 CFU of P. aeruginosa (ATCC 27853). On day 3 post-infection, animals were treated daily, for 3 consecutive days, with saline, plain liposomes, free polymyxin B or liposomal polymyxin B (2 mg PmB/kg body weight) by intratracheal instillation; animals were killed 24 h after the third drug instillation. Treatment of infected animals with liposomal polymyxin B significantly reduced the pulmonary bacterial counts (3.7 ± 0.4 log CFU/paired lungs) as compared to that of free polymyxin B (5.1 ± 0.2 log CFU/paired lungs). Treatment of infected animals with plain liposomes gave similar pulmonary bacterial counts to those obtained from saline-treated group. Pulmonary infection with P. aeruginosa also resulted in lung injury as evidenced by increases in wet lung weight and decreases in angiotensin converting enzyme activity as well as increases in myeloperoxidase activity, an index of the inflammatory response. Treatment with free polymyxin B ameliorated the lung injuries induced by the microorganism and this protective effect was more pronounced in the liposomal polymyxin B-treated group. The levels of polymyxin B in lungs of i

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Keywords
Liposomes;Polymyxin B;Lung infection;Pseudomonas aeruginosa;Antibacterial drugs;Lung injuries;Lung injury
Report Number
DCIEM-SL-2001-051 — Scientific Literature
Date of publication
01 Jan 2002
Number of Pages
7
DSTKIM No
CA023178
CANDIS No
520380
Format(s):
Electronic Document(PDF);CD ROM

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