| The diarylquinoline TMC207 for multidrug-resistant tuberculosis. | |
| | |
MedLine Citation:
|
PMID: 19494215 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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 log(10) 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.) |
| | |
Authors:
|
Andreas H Diacon; Alexander Pym; Martin Grobusch; Ramonde Patientia; Roxana Rustomjee; Liesl Page-Shipp; Christoffel Pistorius; Rene Krause; Mampedi Bogoshi; Gavin Churchyard; Amour Venter; Jenny Allen; Juan Carlos Palomino; Tine De Marez; Rolf P G van Heeswijk; Nacer Lounis; Paul Meyvisch; Johan Verbeeck; Wim Parys; Karel de Beule; Koen Andries; David F Mc Neeley |
Related Documents
:
|
23029435 - Mediating role of activity level in the depressive realism effect. 20368815 - Intermittent preventive treatment in infants for the prevention of malaria in rural wes... 12413615 - A randomized comparative study on mifepristone alone and in combination with tamoxifen ... 11126255 - Hemodynamic aspects and oxygenation variables in severe malaria of adults in africa. 23210025 - Cognitive function of korean neurosurgical patients: cross-sectional study using the ko... 12167135 - Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled,... |
Publication Detail:
|
Type: Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial |
Journal Detail:
|
Title: The New England journal of medicine Volume: 360 ISSN: 1533-4406 ISO Abbreviation: N. Engl. J. Med. Publication Date: 2009 Jun |
Date Detail:
|
Created Date: 2009-06-04 Completed Date: 2009-06-12 Revised Date: 2013-04-10 |
Medline Journal Info:
|
Nlm Unique ID: 0255562 Medline TA: N Engl J Med Country: United States |
Other Details:
|
Languages: eng Pagination: 2397-405 Citation Subset: AIM; IM |
Copyright Information:
|
2009 Massachusetts Medical Society |
Affiliation:
|
Centre for Clinical Tuberculosis Research, the Department of Science and Technology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, all in South Africa. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
ClinicalTrials.gov/NCT00449644 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Antitubercular Agents / adverse effects, pharmacokinetics, therapeutic use* Colony Count, Microbial Drug Therapy, Combination Female Humans Male Microbial Sensitivity Tests Middle Aged Mycobacterium tuberculosis / drug effects*, enzymology, growth & development Proton-Translocating ATPases / antagonists & inhibitors* Quinolines / adverse effects, pharmacokinetics, therapeutic use* Tuberculosis, Multidrug-Resistant / drug therapy* Young Adult |
| Chemical | |
Reg. No./Substance:
|
0/Antitubercular Agents; 0/Quinolines; 78846I289Y/Bedaquiline; EC 3.6.3.14/Proton-Translocating ATPases |
| Comments/Corrections | |
Comment In:
|
N Engl J Med. 2009 Jun 4;360(23):2466-7
[PMID:
19494223
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The relationship between retinal ganglion cell axon constituents and retinal nerve fiber layer biref...
Next Document: Overseas screening for tuberculosis in U.S.-bound immigrants and refugees.