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 Table of Contents    
Year : 2016  |  Volume : 48  |  Issue : 4  |  Page : 466

Bedaquiline versus placebo for management of multidrug-resistant tuberculosis: A systematic review

Department of Pharmacology, AIIMS, Jodhpur, Rajasthan, India

Date of Web Publication13-Jul-2016

Correspondence Address:
Pramod Kumar Sharma
Department of Pharmacology, AIIMS, Jodhpur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7613.186196

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How to cite this article:
Singh S, Sharma PK, Kaur R. Bedaquiline versus placebo for management of multidrug-resistant tuberculosis: A systematic review. Indian J Pharmacol 2016;48:466

How to cite this URL:
Singh S, Sharma PK, Kaur R. Bedaquiline versus placebo for management of multidrug-resistant tuberculosis: A systematic review. Indian J Pharmacol [serial online] 2016 [cited 2023 May 30];48:466. Available from: https://www.ijp-online.com/text.asp?2016/48/4/466/186196


Charan et al. compared time to conversion of positive sputum to negative and mortality between bedaquiline and placebo. In all the forest plots as heterogenicity, I2 = 0% or nonsignificant, they should have pooled data under fixed-effect model rather than using random effect model. We have certain observations that need clarifications. Authors' conclusion with regard to increased mortality associated with bedaquiline cannot be ascertained as the authors of the bedaquiline trial [1] stated that no causal pattern was evident to bedaquiline use. Moreover, mortality in a meta-analysis [2] involving 9153 patients with multidrug-resistant tuberculosis (MDR-TB) was 15% and in another open-label, phase II trial [3] of bedaquiline in 233 patients with newly diagnosed or previously treated MDR-TB was 7%. In a study by Diacon et al., there were significantly more number of HIV-positive patients in placebo group (P = 0.04). We expect that antiretroviral therapy would have resulted in reduced mortality in placebo group as compared to bedaquiline.[4],[5] Not only there was increased background resistance to second-line drugs in bedaquiline group, but also significantly more number of patients in the placebo group had at least one new antitubercular drug added to their background regimen (58% vs. 47%). Finally, comparing mortality in phase II trial of bedaquiline [1] would have resulted in an alpha error of 0.45, i.e., 45% as mortality was the ninth comparison (two analysis for sputum conversion, five subgroups, and one-drug resistance analysis). Thus, concluding falsely decreased Mortality in placebo and increased mortality in bedaquiline group in this meta-analysis by Charan et al. without considering the above-stated factors is not warranted. Considering 15% mortality in MDR-TB [2] from such a large patient pool it becomes difficult to explain 2% mortality in placebo groups of the studied selected for this meta-analysis. Thus, we assume that the authors' conclusion of bedaquiline associated increase in mortality was based on wrong interpretation of published literature.

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  References Top

Diacon AH, Pym A, Grobusch MP, de los Rios JM, Gotuzzo E, Vasilyeva I, et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med 2014;371:723-32.  Back to cited text no. 1
Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bauer M, Bayona JN, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: An individual patient data meta-analysis of 9,153 patients. PLoS Med 2012;9:e1001300.  Back to cited text no. 2
Pym A, Diacon A, Conradie F, Tang S, Bakare N, Haxaire-Theeuwes M, et al. Bedaquiline as part of a multi-drug resistant tuberculosis (MDR-TB) therapy regimen: Final results of a single-arm, phase II trial (C209). Int J Tuberc Lung Dis 2013;17 Suppl 2:S236.  Back to cited text no. 3
Worodria W, Massinga-Loembe M, Mazakpwe D, Luzinda K, Menten J, Van Leth F, et al. Incidence and predictors of mortality and the effect of tuberculosis immune reconstitution inflammatory syndrome in a cohort of TB/HIV patients commencing antiretroviral therapy. J Acquir Immune Defic Syndr 2011;58:32-7.  Back to cited text no. 4
Mycobacterium Tuberculosis Disease with HIV Coinfection | Adult and Adolescent ARV Guidelines. Available from: https://www.aidsinfo.nih.gov/. [Last cited on 2016 May 06].  Back to cited text no. 5


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