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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The diarylquinoline TMC207 for multidrug-resistant tuberculosis
New England Journal of Medicine, Volume 360, No. 23, Year 2009
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Description
BACKGROUND: The diarylquinoline TMC207 offers a new mechanism of antituberculosis action by inhibiting mycobacterial ATP synthase. TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis. METHODS: In the first stage of a two-stage, phase 2, randomized, controlled trial, we randomly assigned 47 patients who had newly diagnosed multidrug-resistant pulmonary tuberculosis to receive either TMC207 (400 mg daily for 2 weeks, followed by 200 mg three times a week for 6 weeks) (23 patients) or placebo (24 patients) in combination with a standard five-drug, second-line antituberculosis regimen. The primary efficacy end point was the conversion of sputum cultures, in liquid broth, from positive to negative. RESULTS: The addition of TMC207 to standard therapy for multidrug-resistant tuberculosis reduced the time to conversion to a negative sputum culture, as compared with placebo (hazard ratio, 11.8; 95% confidence interval, 2.3 to 61.3; P = 0.003 by Cox regression analysis) and increased the proportion of patients with conversion of sputum culture (48% vs. 9%). The mean log10 count of colony-forming units in the sputum declined more rapidly in the TMC207 group than in the placebo group. No significant differences in average plasma TMC207 concentrations were noted between patients with and those without culture conversion. Most adverse events were mild to moderate, and only nausea occurred significantly more frequently among patients in the TMC207 group than among patients in the placebo group (26% vs. 4%, P = 0.04). CONCLUSIONS: The clinical activity of TMC207 validates ATP synthase as a viable target for the treatment of tuberculosis. (ClinicalTrials.gov number, NCT00449644.). Copyright © 2009 Massachusetts Medical Society.
Authors & Co-Authors
Diacon, Andreas Henri
South Africa, Stellenbosch
Stellenbosch University
Pym, Alexander S.
South Africa, Tygerberg
South African Medical Research Council
Grobusch, Martín Peter
South Africa, Johannesburg
University of the Witwatersrand Faculty of Health Sciences
Patientia, R. F.
South Africa, Stellenbosch
Stellenbosch University
Rustomjee, Roxana
South Africa, Tygerberg
South African Medical Research Council
Page-Shipp, Liesl Shirley
South Africa, Johannesburg
Right to Care
Pistorius, Christoffel
South Africa, Port Elizabeth
Jose Pearson Hospital
Krause, Rene
South Africa, George
Harry Comay Hospital
Bogoshi, Mampedi
South Africa, Johannesburg
The Aurum Institute
Churchyard, Gavin John
South Africa, Johannesburg
The Aurum Institute
Venter, Amour
South Africa, Stellenbosch
Stellenbosch University
Allen, Jenny
South Africa, Tygerberg
South African Medical Research Council
Palomino, Juan Carlos
Belgium, Antwerpen
Prins Leopold Instituut Voor Tropische Geneeskunde
De Marez, T.
United States, Philadelphia
Tibotec Inc.
van Heeswijk, Rolf P.G.
Belgium, Machelen
Tibotec Bvba
Lounis, Nacer
Belgium, Machelen
Tibotec Bvba
Meyvisch, Paul
Belgium, Machelen
Tibotec Bvba
Verbeeck, Johan
Belgium, Machelen
Tibotec Bvba
Parys, Wim
Belgium, Machelen
Tibotec Bvba
De Beule, K.
Belgium, Machelen
Tibotec Bvba
Andries, K.
Belgium, Machelen
Tibotec Bvba
Mc Neeley, David F.
United States, Philadelphia
Tibotec Inc.
Statistics
Citations: 752
Authors: 22
Affiliations: 10
Identifiers
Doi:
10.1056/NEJMoa0808427
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Environmental
Study Approach
Quantitative