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Sterilizing activity of thioridazine in combination with the first-line regimen against acute murine tuberculosis
Noton K Dutta1, Michael L Pinn1, Petros C Karakousis2
1Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract:
We recently reported that in lung tissue, thioridazine accumulates at high concentrations relative to serum levels, displaying modest synergy with isoniazid and reducing the emergence of isoniazid-resistant mutants in mouse lungs. In this study, we sought to investigate the sterilizing activity of human-equivalent doses of thioridazine when given in combination with the "Denver regimen" against acute murine tuberculosis. We found a trend toward a positive impact of thioridazine on the bacterial clearance and lowering relapse rates of the combined standard TB chemotherapy.
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