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New Antituberculosis Drugs: From Clinical Trial to Programmatic Use

Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensit...

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Autores principales: Gualano, Gina, Capone, Susanna, Matteelli, Alberto, Palmieri, Fabrizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927937/
https://www.ncbi.nlm.nih.gov/pubmed/27403268
http://dx.doi.org/10.4081/idr.2016.6569
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author Gualano, Gina
Capone, Susanna
Matteelli, Alberto
Palmieri, Fabrizio
author_facet Gualano, Gina
Capone, Susanna
Matteelli, Alberto
Palmieri, Fabrizio
author_sort Gualano, Gina
collection PubMed
description Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of in-patient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance.
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spelling pubmed-49279372016-07-11 New Antituberculosis Drugs: From Clinical Trial to Programmatic Use Gualano, Gina Capone, Susanna Matteelli, Alberto Palmieri, Fabrizio Infect Dis Rep Review Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of in-patient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance. PAGEPress Publications, Pavia, Italy 2016-06-24 /pmc/articles/PMC4927937/ /pubmed/27403268 http://dx.doi.org/10.4081/idr.2016.6569 Text en ©Copyright G. Gualano et al. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Gualano, Gina
Capone, Susanna
Matteelli, Alberto
Palmieri, Fabrizio
New Antituberculosis Drugs: From Clinical Trial to Programmatic Use
title New Antituberculosis Drugs: From Clinical Trial to Programmatic Use
title_full New Antituberculosis Drugs: From Clinical Trial to Programmatic Use
title_fullStr New Antituberculosis Drugs: From Clinical Trial to Programmatic Use
title_full_unstemmed New Antituberculosis Drugs: From Clinical Trial to Programmatic Use
title_short New Antituberculosis Drugs: From Clinical Trial to Programmatic Use
title_sort new antituberculosis drugs: from clinical trial to programmatic use
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927937/
https://www.ncbi.nlm.nih.gov/pubmed/27403268
http://dx.doi.org/10.4081/idr.2016.6569
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