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Multidrug-resistant tuberculosis and culture conversion with bedaquiline.
N Engl J Med 2014; 371(8):723-32NEJM

Abstract

BACKGROUND

Bedaquiline (Sirturo, TMC207), a diarylquinoline that inhibits mycobacterial ATP synthase, has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis, when added to a preferred background regimen for 8 weeks.

METHODS

In this phase 2b trial, we randomly assigned 160 patients with newly diagnosed, smear-positive, multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks, followed by 200 mg three times a week for 22 weeks, or placebo, both in combination with a preferred background regimen. The primary efficacy end point was the time to sputum-culture conversion in liquid broth. Patients were followed for 120 weeks from baseline.

RESULTS

Bedaquiline reduced the median time to culture conversion, as compared with placebo, from 125 days to 83 days (hazard ratio in the bedaquiline group, 2.44; 95% confidence interval, 1.57 to 3.80; P<0.001 by Cox regression analysis) and increased the rate of culture conversion at 24 weeks (79% vs. 58%, P=0.008) and at 120 weeks (62% vs. 44%, P=0.04). On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis, cure rates at 120 weeks were 58% in the bedaquiline group and 32% in the placebo group (P=0.003). The overall incidence of adverse events was similar in the two groups. There were 10 deaths in the bedaquiline group and 2 in the placebo group, with no causal pattern evident.

CONCLUSIONS

The addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversions at 120 weeks, as compared with placebo. There were more deaths in the bedaquiline group than in the placebo group. (Funded by Janssen Pharmaceuticals; TMC207-C208 ClinicalTrials.gov number, NCT00449644.).

Authors+Show Affiliations

The authors' affiliations are provided in the Appendix.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25140958

Citation

Diacon, Andreas H., et al. "Multidrug-resistant Tuberculosis and Culture Conversion With Bedaquiline." The New England Journal of Medicine, vol. 371, no. 8, 2014, pp. 723-32.
Diacon AH, Pym A, Grobusch MP, et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014;371(8):723-32.
Diacon, A. H., Pym, A., Grobusch, M. P., de los Rios, J. M., Gotuzzo, E., Vasilyeva, I., ... Dannemann, B. (2014). Multidrug-resistant tuberculosis and culture conversion with bedaquiline. The New England Journal of Medicine, 371(8), pp. 723-32. doi:10.1056/NEJMoa1313865.
Diacon AH, et al. Multidrug-resistant Tuberculosis and Culture Conversion With Bedaquiline. N Engl J Med. 2014 Aug 21;371(8):723-32. PubMed PMID: 25140958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multidrug-resistant tuberculosis and culture conversion with bedaquiline. AU - Diacon,Andreas H, AU - Pym,Alexander, AU - Grobusch,Martin P, AU - de los Rios,Jorge M, AU - Gotuzzo,Eduardo, AU - Vasilyeva,Irina, AU - Leimane,Vaira, AU - Andries,Koen, AU - Bakare,Nyasha, AU - De Marez,Tine, AU - Haxaire-Theeuwes,Myriam, AU - Lounis,Nacer, AU - Meyvisch,Paul, AU - De Paepe,Els, AU - van Heeswijk,Rolf P G, AU - Dannemann,Brian, AU - ,, PY - 2014/8/21/entrez PY - 2014/8/21/pubmed PY - 2014/9/3/medline SP - 723 EP - 32 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 371 IS - 8 N2 - BACKGROUND: Bedaquiline (Sirturo, TMC207), a diarylquinoline that inhibits mycobacterial ATP synthase, has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis, when added to a preferred background regimen for 8 weeks. METHODS: In this phase 2b trial, we randomly assigned 160 patients with newly diagnosed, smear-positive, multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks, followed by 200 mg three times a week for 22 weeks, or placebo, both in combination with a preferred background regimen. The primary efficacy end point was the time to sputum-culture conversion in liquid broth. Patients were followed for 120 weeks from baseline. RESULTS: Bedaquiline reduced the median time to culture conversion, as compared with placebo, from 125 days to 83 days (hazard ratio in the bedaquiline group, 2.44; 95% confidence interval, 1.57 to 3.80; P<0.001 by Cox regression analysis) and increased the rate of culture conversion at 24 weeks (79% vs. 58%, P=0.008) and at 120 weeks (62% vs. 44%, P=0.04). On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis, cure rates at 120 weeks were 58% in the bedaquiline group and 32% in the placebo group (P=0.003). The overall incidence of adverse events was similar in the two groups. There were 10 deaths in the bedaquiline group and 2 in the placebo group, with no causal pattern evident. CONCLUSIONS: The addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversions at 120 weeks, as compared with placebo. There were more deaths in the bedaquiline group than in the placebo group. (Funded by Janssen Pharmaceuticals; TMC207-C208 ClinicalTrials.gov number, NCT00449644.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/25140958/Multidrug_resistant_tuberculosis_and_culture_conversion_with_bedaquiline_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa1313865?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -