title: Mechanisms by which thioridazine in combination with antibiotics cures extensively drug-resistant infections of pulmonary tuberculosis.
abstract: Advances recently introduced into the Clinical Mycobacteriology Laboratory of the Institute of Hygiene and Tropical Medicine, such that a multi-drug resistant infection of pulmonary tuberculosis (MDR TB) can be identified within one day of receiving the sputum specimen, have greatly contributed to the reduction of the frequency of these infections. However, approximately 50% of reduced infections exhibit a phenotype that is consistent with that presented by an extensively drug-resistant (XDR) infection. More effective agents were required and hence attention was attributed to the possibility that the old neuroleptic phenothiazine thioridazine (TZ), previously shown to inhibit the growth of all encountered strains of Mycobacterium tuberculosis (Mtb) regardless of their antibiotic resistance profile, could be eventually used for therapy of problematic MDR/XDR TB infections. This mini-review discusses the mechanisms that render TZ an effective adjuvant to antibiotics to which the initial infective agent Mtb was resistant.
authors.affiliation: Travel Medicine of the Center de Malaria e Doencas Tropicais, Institute of Hygiene and Tropical Medicine,Universidade Nova de Lisboa, Lisbon, Portugal. lamaral@ihmt.unl.pt.
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology*; D013881:Thioridazine / Q000494:pharmacology* / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D013881:Thioridazine
keywords: Mycobacterium tuberculosis; Tuberculosis; efflux pumps; killing activity; lysosome; macrophages; phagolysosome; phagosome; phenothiazines; review; thioridazine