Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8738722 | International Journal of Antimicrobial Agents | 2018 | 5 Pages |
Abstract
Tuberculosis (TB) has been the scourge of the human race for many decades, claiming countless number of lives. This is further complicated by the ability of Mycobacterium tuberculosis to infect extrapulmonary sites, specifically the brain. These extrapulmonary forms of TB are difficult to treat owing to problems associated with drug delivery across the blood-brain barrier. Linezolid (LIN) and clofazimine (CFZ) are two of the more promising anti-TB drugs in recent times. In this study, BALB/c mice were aerosol-infected with M. tuberculosis H37Rv and were treated for 4 weeks with LIN [100âmg/kg body weight (BW)] or CFZ (100âmg/kg BW). Concurrently, it was investigated whether an aerosol TB infection would lead to dissemination of TB bacilli into the brain. Post-treatment brain and lung CFUs were determined together with serum, lung and brain drug concentrations. CFZ displayed a strong bactericidal effect in the lung, whilst LIN had a bacteriostatic effect. Mycobacterium tuberculosis appeared at 2 weeks post-infection in the untreated group (2.38â±â0.43 log10 CFU) and more surprisingly at 3 weeks post-infection in the LIN-treated group (1.14â±â0.99 log10 CFU). TB bacilli could not be detected in the brains of the CFZ-treated group. To the best of our knowledge, this is the first study showing the appearance of M. tuberculosis in the brain following a murine aerosol TB infection. This study may advocate the use of CFZ as prophylactic treatment to prevent the development of extrapulmonary TB of the central nervous system using a two-pronged approach.
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Authors
Sooraj Baijnath, Chivonne Moodley, Bongani Ngcobo, Sanil D. Singh, Hendrik G. Kruger, Per I. Arvidsson, Tricia Naicker, Alexander Pym, Thavendran Govender,