dc.contributor.author |
Diacon, Andreas H. |
|
dc.contributor.author |
Pym, Alexander |
|
dc.contributor.author |
Grobusch, Martin P. |
|
dc.contributor.author |
De Los Rios, Jorge M. |
|
dc.contributor.author |
Gotuzzo Herencia, José Eduardo |
|
dc.contributor.author |
Vasilyeva, Irina |
|
dc.contributor.author |
Leimane, Vaira |
|
dc.contributor.author |
Andries, Koen |
|
dc.contributor.author |
Bakare, Nyasha |
|
dc.contributor.author |
De Marez, Tine |
|
dc.contributor.author |
Haxaire-Theeuwes, Myriam |
|
dc.contributor.author |
Lounis, Nacer |
|
dc.contributor.author |
Meyvisch, Paul |
|
dc.contributor.author |
De Paepe, Els |
|
dc.contributor.author |
Van Heeswijk, Rolf P.G. |
|
dc.contributor.author |
Dannemann, Brian |
|
dc.date.accessioned |
2020-06-10T18:12:14Z |
|
dc.date.available |
2020-06-10T18:12:14Z |
|
dc.date.issued |
2014 |
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dc.identifier.uri |
https://hdl.handle.net/20.500.12866/8066 |
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dc.description.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. |
en_US |
dc.language.iso |
eng |
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dc.publisher |
Massachusetts Medical Society |
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dc.relation.ispartofseries |
New England Journal of Medicine |
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dc.rights |
info:eu-repo/semantics/restrictedAccess |
|
dc.rights.uri |
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es |
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dc.subject |
Adolescent |
en_US |
dc.subject |
Adult |
en_US |
dc.subject |
Female |
en_US |
dc.subject |
Humans |
en_US |
dc.subject |
Male |
en_US |
dc.subject |
Young Adult |
en_US |
dc.subject |
Mycobacterium tuberculosis |
en_US |
dc.subject |
Sputum |
en_US |
dc.subject |
Middle Aged |
en_US |
dc.subject |
Drug Therapy, Combination |
en_US |
dc.subject |
pyrazinamide |
en_US |
dc.subject |
Tuberculosis, Multidrug-Resistant |
en_US |
dc.subject |
human |
en_US |
dc.subject |
adult |
en_US |
dc.subject |
aged |
en_US |
dc.subject |
female |
en_US |
dc.subject |
male |
en_US |
dc.subject |
incidence |
en_US |
dc.subject |
priority journal |
en_US |
dc.subject |
controlled study |
en_US |
dc.subject |
major clinical study |
en_US |
dc.subject |
article |
en_US |
dc.subject |
ethambutol |
en_US |
dc.subject |
drug efficacy |
en_US |
dc.subject |
headache |
en_US |
dc.subject |
disease severity |
en_US |
dc.subject |
kanamycin |
en_US |
dc.subject |
placebo |
en_US |
dc.subject |
Drug Administration Schedule |
en_US |
dc.subject |
Antitubercular Agents |
en_US |
dc.subject |
multicenter study |
en_US |
dc.subject |
minimum inhibitory concentration |
en_US |
dc.subject |
quinolone derivative |
en_US |
dc.subject |
isoniazid |
en_US |
dc.subject |
multidrug resistant tuberculosis |
en_US |
dc.subject |
rifampicin |
en_US |
dc.subject |
drug dose reduction |
en_US |
dc.subject |
drug safety |
en_US |
dc.subject |
drug withdrawal |
en_US |
dc.subject |
phase 2 clinical trial |
en_US |
dc.subject |
randomized controlled trial |
en_US |
dc.subject |
sputum culture |
en_US |
dc.subject |
drug sensitivity |
en_US |
dc.subject |
arthralgia |
en_US |
dc.subject |
cause of death |
en_US |
dc.subject |
ethionamide |
en_US |
dc.subject |
antibacterial activity |
en_US |
dc.subject |
nausea |
en_US |
dc.subject |
vomiting |
en_US |
dc.subject |
treatment duration |
en_US |
dc.subject |
hemoptysis |
en_US |
dc.subject |
double blind procedure |
en_US |
dc.subject |
unspecified side effect |
en_US |
dc.subject |
aminoglycoside |
en_US |
dc.subject |
bedaquiline |
en_US |
dc.subject |
cycloserine |
en_US |
dc.subject |
protionamide |
en_US |
dc.subject |
hyperuricemia |
en_US |
dc.subject |
Diarylquinolines |
en_US |
dc.subject |
ofloxacin |
en_US |
dc.subject |
antimycobacterial activity |
en_US |
dc.subject |
Intention to Treat Analysis |
en_US |
dc.subject |
sputum culture conversion |
en_US |
dc.subject |
terizidone |
en_US |
dc.title |
Multidrug-resistant tuberculosis and culture conversion with bedaquiline |
en_US |
dc.type |
info:eu-repo/semantics/article |
|
dc.identifier.doi |
https://doi.org/10.1056/NEJMoa1313865 |
|
dc.subject.ocde |
https://purl.org/pe-repo/ocde/ford#3.02.00 |
|
dc.relation.issn |
1533-4406 |
|