title: Sterilizing activity of thioridazine in combination with the first-line regimen against acute murine tuberculosis.
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.
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Noton K
authors.initials: NK
authors.lastname: Dutta
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pinn
authors.affiliation: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA petros@jhmi.edu.
authors.forename: Petros C
authors.initials: PC
authors.lastname: Karakousis
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007538:Isoniazid / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013881:Thioridazine / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D013881:Thioridazine; D007538:Isoniazid; D012293:Rifampin