6
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually every drug in use. Courses of therapy select for these mutants and drug-resistant organisms emerge. The development of drug-resistant organisms has reached the point that drug resistance now threatens to undermine global success against tuberculosis (TB). New drugs are needed. The last new class of drugs specifically developed for treatment of TB was the rifamycins over 40 years ago. New funding sources and the development of product development partnerships have energized the TB drug development effort. There are now more TB drugs in development than at any time in the past. The first of these drugs to be developed and marketed was bedaquiline. Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport. This raises the exciting possibility that bedaquiline may be active against less metabolically active organisms. Drug–drug interactions between rifamycins and the cytochrome P450-3A system will limit bedaquiline’s utility and create complexity in treatment regimens. In clinical trials, treatment with bedaquiline added to a background multidrug-resistant TB regimen was associated with earlier culture conversion and higher cure rates, but there were unexplained excess deaths in the bedaquiline arms of these trials. Food and Drug Administration approved bedaquiline for the treatment of multidrug-resistant TB when an effective treatment regimen cannot otherwise be provided. They required a black box warning about excess deaths and require that a phase III trial be completed. A planned Phase III trial is being reorganized. While bedaquiline is an exciting drug and marks a dramatic moment in the history of TB treatment, its ultimate place in the anti-TB drug armamentarium is unclear pending the Phase III trial and the development of other new drugs that are in the pipeline.

          Related collections

          Most cited references 38

          • Record: found
          • Abstract: not found
          • Article: not found

          American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic.

            This article describes the global epidemiology of tuberculosis and reviews recent estimates of tuberculosis incidence and mortality in the world. The highest prevalence of tuberculosis infection and estimated annual risk of tuberculosis infection are in sub-Saharan Africa and Southeast Asia. Overall, almost 3.8 million cases of tuberculosis were reported in the world in 1990, of which 49% were in Southeast Asia. From the period 1984 through 1986 to the period 1989 through 1991, notification rates increased in all World Health Organization regions, except the American and the European regions. In 1990, there were an estimated 7.5 million cases of tuberculosis and 2.5 million deaths worldwide. The human immunodeficiency virus epidemic is causing increases in the number of tuberculosis cases, particularly in Africa, although increases are also expected in Southeast Asia. In many industrialized countries, tuberculosis has recently failed to decline, and in eastern Europe and the former Soviet Union, cases and deaths are increasing. Drug resistance is a serious problem, especially in the United States. If worldwide control of tuberculosis does not improve, 90 million new cases and 30 million deaths are expected in the decade 1990 through 1999.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Global epidemiology of tuberculosis

                Bookmark

                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2014
                29 July 2014
                : 10
                : 597-602
                Affiliations
                Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, NY, USA
                Author notes
                Correspondence: Eric Leibert, New York University School of Medicine, 462 First Avenue, 7-N-24, New York, NY, USA 10016, Tel +1 212 263 6479, Fax +1 212 263 8442, Email eric.leibert@ 123456nyumc.org
                Article
                tcrm-10-597
                10.2147/TCRM.S37743
                4122575
                25114537
                © 2014 Leibert et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Medicine

                sirturo, multidrug-resistant tuberculosis, bedaquiline

                Comments

                Comment on this article