Characterisation of a refined rat model of respiratory infection with Pseudomonas aeruginosa and the effect of ciprofloxacin

被引:17
作者
Growcott, E. J. [1 ]
Coulthard, A. [1 ]
Amison, R. [1 ]
Hardaker, E. L. [1 ]
Saxena, V. [2 ]
Malt, L. [2 ]
Jones, P. [1 ]
Grevot, A. [3 ]
Poll, C. [1 ]
Osborne, C. [2 ]
Banner, K. H. [1 ]
机构
[1] Novartis Inst Biomed Res, Horsham RH12 5AB, W Sussex, England
[2] Novartis Inst Biomed Res, Cambridge, MA 02139 USA
[3] Novartis Pharma AG, CH-4057 Basel, Switzerland
关键词
Pseudomonas aeruginosa; Agar beads; Ciprofloxacin; SUPPRESSES BACTERIAL PROLIFERATION; CYSTIC-FIBROSIS MICE; LUNG INFECTION; INFLAMMATION; PNEUMONIA; THERAPY;
D O I
10.1016/j.jcf.2010.12.007
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: We sought to characterise a refined rat model of respiratory infection with P. aeruginosa over an acute time course and test the antibiotic ciprofloxacin. Methods: Agar beads were prepared +/- SPAN (R) 80. Rats were inoculated with sterile agar beads or those containing 10(5) colony forming units (cfu) P. aeruginosa via intra-tracheal dosing. Bacterial load and inflammatory parameters were measured. Results: Differing concentrations of SPAN (R) 80 modified median agar bead diameter and reduced particle size distribution. Beads prepared with 0.01% v/v SPAN (R) 80 were evaluated in vivo. A stable lung infection up to 7 days post infection was achieved and induced BALF neutrophilia 2 and 5 days post infection. Ciprofloxacin (50 mg/kg) significantly attenuated infection without affecting the inflammatory parameters measured. Conclusion: SPAN (R) 80 can control the particle size and lung distribution of agar beads and P. aeruginosa-embedded beads prepared with 0.01%v/v SPAN (R) 80 can induce infection and inflammation over 7 days. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:166 / 174
页数:9
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