Aerosol Infection Model of Tuberculosis in Wistar RatsReport as inadecuate




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International Journal of MicrobiologyVolume 2010 2010, Article ID 426035, 6 pages

Research ArticleAstraZeneca India Pvt. Ltd., Bellary Road, Hebbal, Bangalore 560024, India

Received 13 August 2009; Revised 24 December 2009; Accepted 5 January 2010

Academic Editor: Joseph Falkinham

Copyright © 2010 Sheshagiri Gaonkar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We explored suitability of a rat tuberculosis aerosol infection model for investigating the pharmacodynamics of new antimycobacterial agents. Infection of rats via the aerosol route led to a reproducible course of M. tuberculosis infection in the lungs. The pulmonary bacterial load increased logarithmically during the first six weeks, thereafter, the infection stabilized for the next 12 weeks. We observed macroscopically visible granulomas in the lungs with demonstrable acid-fast bacilli and associated histopathology. Rifampicin RIF at a dose range of 30 to 270 mg-kg exhibited a sharp dose response while isoniazid INH at a dose range of 10 to 90 mg-kg and ethambutol EMB at 100 to 1000 mg-kg showed shallow dose responses. Pyrazinamide PZA had no dose response between 300 and 1000 mg-kg dose range. In a separate time kill study at fixed drug doses RIF 90 mg-kg, INH 30 mg-kg, EMB 300 mg-kg, and PZA 300 mg-kg the bactericidal effect of all the four drugs increased with longer duration of treatment from two weeks to four weeks. The observed infection profile and therapeutic outcomes in this rat model suggest that it can be used as an additional, pharmacologically relevant efficacy model to develop novel antitubercular compounds at the interface of discovery and development.





Author: Sheshagiri Gaonkar, Sowmya Bharath, Naveen Kumar, V. Balasubramanian, and Radha K. Shandil

Source: https://www.hindawi.com/



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