title: Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies.
abstract: WHO estimates that 9 million people developed active tuberculosis in 2013 and 1·5 million people died from it. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis continue to spread worldwide with an estimated 480,000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis are still low and development of new, more effective tuberculosis drugs and adjunct therapies to improve treatment outcomes are urgently needed. Although standard therapy for drug-sensitive tuberculosis is highly effective, shorter, more effective treatment regimens are needed to reduce the burden of infectious cases. We review the latest WHO guidelines and global recommendations for treatment and management of drug-sensitive and drug-resistant tuberculosis, and provide an update on new drug development, results of several phase 2 and phase 3 tuberculosis treatment trials, and other emerging adjunct therapeutic options for MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and gatifloxacin) regimens have failed to shorten duration of therapy, and the new tuberculosis drug pipeline is sparse. Scale-up of existing interventions with increased investments into tuberculosis health services, development of new antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary political leadership, are still our best chance to change the unacceptable status quo of the tuberculosis situation worldwide and the growing problem of drug-resistant tuberculosis.
authors.affiliation: Division of Infection and Immunity, University College London and National Institute for Health Research (NIHR) Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK; UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia. Electronic address: a.zumla@ucl.ac.uk.
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.affiliation: Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Chakaya
authors.affiliation: WHO Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione Salvatorie Maugeri, Care and Research Institute, Tradate, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Centis
authors.affiliation: WHO Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione Salvatorie Maugeri, Care and Research Institute, Tradate, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: D'Ambrosio
authors.affiliation: UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mwaba
authors.affiliation: UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bates
authors.affiliation: National Tuberculosis Programme, Ministry of Community Development, Ministry of Health, Lusaka, Zambia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Kapata
authors.affiliation: European Developing Countries Clinical Trials Partnership, Cape Town, South Africa.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyirenda
authors.affiliation: UNZA-UCLMS Research and Training Project, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chanda
authors.affiliation: National Institute for Medical Research, Muhumbili, Tanzania.
authors.forename: Sayoki
authors.initials: S
authors.lastname: Mfinanga
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, and German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: Therapeutic Immunology, Departments of Laboratory Medicine, Karolinska Institutet and Center for Allogeneic Stem Cell Transplantation, CAST, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
authors.affiliation: WHO Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione Salvatorie Maugeri, Care and Research Institute, Tradate, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Migliori
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D060085:Coinfection / Q000150:complications / Q000188:drug therapy; D055808:Drug Discovery; D004359:Drug Therapy, Combination; D014943:Global Health; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D009169:Mycobacterium tuberculosis; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications / Q000188:drug therapy*; D014944:World Health Organization
chemical_list: D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; D000995:Antitubercular Agents