title: Clinical research in the treatment of tuberculosis: current status and future prospects.
abstract: To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease.
authors.affiliation: Tuberculosis and Chest Service, Department of Health, Hong Kong, China.
authors.forename: K-C
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: W-W
authors.initials: WW
authors.lastname: Yew
authors.affiliation: Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari, Italy; Research, Medical Education and Professional Development Unit, Azienda Ospedaliero Universitaria di Sassari, Sassari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sotgiu
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D035843:Biomedical Research / Q000639:trends*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones / Q000008:administration & dosage; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin