Clofazimine protects against Mycobacterium tuberculosis dissemination in the central nervous system following aerosol challenge in a murine model.
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Baijnath S, Moodley C, Ngcobo B, Singh SD, Kruger HG, Arvidsson PI, Naicker T, Pym A, Govender T
Int. J. Antimicrob. Agents 51 (1) 77-81 [2018-01-00; online 2017-08-24]
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 [100 mg/kg body weight (BW)] or CFZ (100 mg/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 (2.38 ± 0.43 log
PubMed 28843822
DOI 10.1016/j.ijantimicag.2017.08.020
Crossref 10.1016/j.ijantimicag.2017.08.020
pii: S0924-8579(17)30312-6