Inadequate dosing and incomplete treatment regimens, coupled with the ability of the tuberculosis bacilli to cause latent infections that are tolerant of currently used drugs, have fueled the rise of multidrug-resistant tuberculosis (MDR-TB). Treatment of MDR-TB infections is a major clinical challenge that has few viable or effective solutions; therefore patients face a poor prognosis and years of treatment. This review focuses on emerging drug classes that have the potential for treating MDR-TB and highlights their particular strengths as leads including their mode of action, in vivo efficacy, and key medicinal chemistry properties. Examples include the newly approved drugs bedaquiline and delaminid, and other agents in clinical and late preclinical development pipeline for the treatment of MDR-TB. Herein, we discuss the challenges to developing drugs to treat tuberculosis and how the field has adapted to these difficulties, with an emphasis on drug discovery approaches that might produce more effective agents and treatment regimens.
Tuberculosis; Antibiotic; Antituberculosis; Drug discovery
Citation: Daniel T. Hoagland, Jiuyu Liu, Robin B. Lee, Richard E. Lee New Agents For The Treatment Of Drug-resistant Mycobacterium Tuberculosis doi:10.1016/j.addr.2016.04.026.
Received: 19 January 2016, Revised: 20 April 2016, Accepted: 22 April 2016, Available online: 2 May 2016
Copyright: © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
This study was supported by U.S. National Institutes of Health (NIH) grants AI090810 and the American Lebanese Syrian Associated Charities, St. Jude Children's Research Hospital. We thank Dr. Angela McArthur for assistance in editing this article and Timothy Hammond for assistance in preparation of the color figures.