title: Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections.
abstract: Thioridazine (TDZ) in combination with antibiotics to which extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) is initially resistant yields a cure. This is due to the fact that TDZ enhances the killing of intracellular M. tuberculosis by non-killing macrophages, inhibits the genetic expression of efflux pumps of M. tuberculosis that extrude antibiotics prior to reaching their intended targets, and inhibits the activity of existing efflux pumps that contribute to the multidrug-resistant phenotype of M. tuberculosis. The combination of these effects of TDZ probably contributes to the successful recent cures of XDR-TB cases when the phenothiazine TDZ is used in combination with antibiotics to which the patient with XDR-TB was initially unresponsive.
authors.affiliation: Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 100, 1049-008 Lisbon, Portugal. lamaral@ihmt.unl.pt
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001693:Biological Transport, Active / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013881:Thioridazine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013881:Thioridazine