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      Profile of delamanid for the treatment of multidrug-resistant tuberculosis

      1 , 2 , 1

      Drug Design, Development and Therapy

      Dove Medical Press

      delamanid, OPC-67683, Deltyba, tuberculosis

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          Abstract

          New approaches to the treatment of multidrug-resistant and extensively drug-resistant tuberculosis (TB) are badly needed. Not only is the success rate of current treatment regimens suboptimal but existing regimens require multiple drugs and lengthy courses and may lead to significant toxicities. The treatment landscape is beginning to shift, however, with the recent approvals of the new TB drugs bedaquiline and delamanid. Delamanid, a dihydro-imidazooxazole, has been shown to have excellent activity against Mycobacterium tuberculosis in both in vitro and in murine TB models. It has also recently been reported to improve rates of sputum culture conversion in patients with multidrug-resistant TB when added to an optimized background regimen. Although generally well tolerated, delamanid has been associated with QT prolongation, which may be of particular clinical concern when paired with other TB drugs that may also have this effect, most notably the fluoroquinolones. Ongoing studies will help to clarify delamanid’s role in the treatment of drug-resistant TB.

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          Most cited references 17

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          Tuberculosis.

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            Antimicrobial-associated QT interval prolongation: pointes of interest.

            Until recently, cardiac toxicity manifesting in the form of arrhythmias related to QT interval prolongation was uncommonly appreciated within the antimicrobial class of drugs, but it was well described among antiarrhythmic agents. Antimicrobials that are associated with QT prolongation include the macrolides/ketolides, certain fluoroquinolones and antimalarials, pentamidine, and the azole antifungals. Although, in most cases, mild delays in ventricular repolarization caused by these drugs are clinically unnoticeable, they may serve to amplify the risk for torsades de pointes (TdP) when prescribed in the setting of other risk factors. Conditions or variables that influence proarrhythmic risk include sex, age, electrolyte derangements, structural heart disease, pharmacokinetic/pharmacodynamic interactions, and genetic predisposition. It is important that clinicians be knowledgeable about drugs with QT liability, as well as the risk factors that increase the probability of TdP. Additionally, because TdP remains a difficult-to-measure adverse event, we must rely upon multiple data sources to determine the risk versus the benefit for newly approved drugs.
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              Assessment of new sterilizing drugs for treating pulmonary tuberculosis by culture at 2 months.

               D A Mitchison (1993)
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                29 January 2015
                : 9
                : 677-682
                Affiliations
                [1 ]Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA
                [2 ]Division of AIDS Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA
                Author notes
                Correspondence: John B Lynch, Harborview Medical Center, 325 9th Avenue, Box 359778, Seattle, WA 98104, USA, Tel +1 206 744 5180, Fax +1 206 744 6564, Email jblynch@ 123456uw.edu
                Article
                dddt-9-677
                10.2147/DDDT.S60923
                4319680
                © 2015 Szumowski and Lynch. 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

                Pharmacology & Pharmaceutical medicine

                tuberculosis, deltyba, opc-67683, delamanid

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