The bactericidal effectiveness of liposomal
polymyxin B against Pseudomonas aeruginosa was investigated in an animal model of pulmonary
infection.
Polymyxin B was incorporated into
liposomes composed of
1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and
cholesterol (Chol) (2:1). Lung
infection was induced in rats following intratracheal instillation of 10(7) colony-forming units (CFU) of P. aeruginosa (ATCC 27853) embedded in
agar beads. Starting on day 3 post-
infection, animals were treated daily, for 3 consecutive days, with saline, empty
liposomes, free
polymyxin B, or liposomal
polymyxin B (2mg
polymyxin B/kg
body weight) by intratracheal instillation; animals were killed 24hr after the third
drug instillation. Treatment of infected animals with liposomal
polymyxin B significantly reduced the pulmonary bacterial counts (3.7+/-0.4log CFU/paired lungs) as compared with that of free
polymyxin B (5.1+/-0.2log CFU/paired lungs). Treatment of infected animals with empty
liposomes gave pulmonary bacterial counts similar to those obtained from the 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, a protective effect that was more pronounced in the liposomal
polymyxin B-treated group. The levels of
polymyxin B in the lungs of the infected animals treated with the liposomal
suspension were significantly higher (42.8+/-6.2 microg/paired lungs) compared with those treated with the free
drug (8.2+/-0.4 microg/paired lungs). These data suggest that direct delivery of liposomal
polymyxin B to the lung can be effective in the treatment of pulmonary
infection with P. aeruginosa by enhancing retention of the
antibiotic in the lung.