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https://www.readbyqxmd.com/read/28630203/bactericidal-and-sterilizing-activity-of-a-novel-regimen-with-bedaquiline-pretomanid-moxifloxacin-and-pyrazinamide-in-a-murine-model-of-tuberculosis
#1
Si-Yang Li, Rokeya Tasneen, Sandeep Tyagi, Heena Soni, Paul J Converse, Khisimuzi Mdluli, Eric L Nuermberger
New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) + pretomanid (PMD) + pyrazinamide (PZA) and of PMD + moxifloxacin (MXF) + PZA shorten the treatment duration necessary to prevent relapse by 2-3 and 1-2 months, respectively, compared with the current first-line regimen in a murine TB model. These 3-drug combinations are now being studied in clinical trials...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28625141/bedaquiline-a-new-hope-for-shorter-and-better-anti-tuberculosis-regimens
#2
Niccolò Riccardi, Filippo Del Puente, Federica Magnè, Lucia Taramasso, Antonio Di Biagio
In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDR-TB). Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; moreover, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for treatment of MDR-TB. BDQ is a diarylquinoline anti-mycobacterial drug, active regardless the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location...
June 19, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28584788/clinical-implications-of-new-drugs-and-regimens-for-the-treatment-of-drug-resistant-tuberculosis
#3
REVIEW
Yong-Soo Kwon
The emergence of drug-resistant tuberculosis (TB) is a growing problem worldwide. The lack of safe and effective drugs, together with the frequent development of adverse drug reactions can result in worse outcomes. Therefore, new TB drugs able to bolster the current TB treatment regimen are urgently required. Novel drugs that are effective and safe against Mycobacterium tuberculosis are required to reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multi-drug-resistant (MDR)-TB...
May 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28533094/population-implications-of-the-use-of-bedaquiline-in-people-with-extensively-drug-resistant-tuberculosis-are-fears-of-resistance-justified
#4
REVIEW
Amber Kunkel, Jennifer Furin, Ted Cohen
Global rollout of the new antituberculosis drug bedaquiline has been slow, in part reflecting concerns about spread of bedaquiline resistance. Acquired resistance to bedaquiline is especially likely in patients with extensively drug-resistant (XDR) tuberculosis. However, the very high mortality rates of patients with XDR not receiving bedaquiline, and promising cohort study results, suggest these patients also have greatest need for the drug. In this Personal View, we argue that resistance concerns should not forestall use of bedaquiline in patients with XDR tuberculosis...
May 19, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28529206/bedaquiline-for-the-treatment-of-multidrug-resistant-tuberculosis-another-missed-opportunity
#5
EDITORIAL
Lorenzo Guglielmetti
No abstract text is available yet for this article.
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28529205/effectiveness-and-safety-of-bedaquiline-containing-regimens-in-the-treatment-of-mdr-and-xdr-tb-a-multicentre-study
#6
Sergey E Borisov, Keertan Dheda, Martin Enwerem, Rodolfo Romero Leyet, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Simon Tiberi, Jan-Willem Alffenaar, Andrey Maryandyshev, Evgeny Belilovski, Shashank Ganatra, Alena Skrahina, Onno Akkerman, Alena Aleksa, Rohit Amale, Janina Artsukevich, Judith Bruchfeld, Jose A Caminero, Isabel Carpena Martinez, Luigi Codecasa, Margareth Dalcolmo, Justin Denholm, Paul Douglas, Raquel Duarte, Aliasgar Esmail, Mohammed Fadul, Alexey Filippov, Lina Davies Forsman, Mina Gaga, Julia-Amaranta Garcia-Fuertes, José-María García-García, Gina Gualano, Jerker Jonsson, Heinke Kunst, Jillian S Lau, Barbara Lazaro Mastrapa, Jorge Lazaro Teran Troya, Selene Manga, Katerina Manika, Pablo González Montaner, Jai Mullerpattan, Suzette Oelofse, Martina Ortelli, Domingo Juan Palmero, Fabrizio Palmieri, Antonella Papalia, Apostolos Papavasileiou, Marie-Christine Payen, Emanuele Pontali, Carlos Robalo Cordeiro, Laura Saderi, Tsetan Dorji Sadutshang, Tatsiana Sanukevich, Varvara Solodovnikova, Antonio Spanevello, Sonam Topgyal, Federica Toscanini, Adrian R Tramontana, Zarir Farokh Udwadia, Pietro Viggiani, Veronica White, Alimuddin Zumla, Giovanni Battista Migliori
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days...
May 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28472892/type-ii-nadh-dehydrogenase-ndh-2-a-promising-therapeutic-target-for-antitubercular-and-antibacterial-drug-discovery
#7
REVIEW
Satheeshkumar Sellamuthu, Meenakshi Singh, Ashok Kumar, Sushil Kumar Singh
Tuberculosis (TB) is highly dangerous due to the development of resistance to first-line drugs. Moreover, Mycobacterium tuberculosis (Mtb) has also developed resistance to newly approved antitubercular drug bedaquiline. This necessitates the search for drugs acting on newer molecular targets. The energy metabolism of mycobacteria is the prime focus for the discovery of novel antitubercular drugs. Targeting type-2 NADH dehydrogenase (NDH-2) involved in the production of respiratory ATP could, therefore, be effective in treating the disease...
June 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28444149/first-two-extensively-drug-resistant-tuberculosis-cases-from-myanmar-treated-with-bedaquiline
#8
Htin Lin Aung, Wint Wint Nyunt, Yang Fong, Gregory M Cook, Si Thu Aung
No abstract text is available yet for this article.
April 24, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28432172/why-tuberculosis-control-programmes-fail-role-of-microlevel-and-macrolevel-factors-an-analysis-from-india
#9
Sudip Bhattacharya, Amarjeet Singh
India accounts for one-fourth of the global tuberculosis (TB) burden. The National TB Program was started in 1962. Over a period of time, some lacunae such as poor case detection rate and incomplete treatment were observed. Later, the government formulated the Revised National Tuberculosis Control Program (RNTCP), which achieved a case detection rate of 70% and a cure rate of 85%. Still, the problem of relapse and defaulter cases persists. In 2014, 6% defaulter cases were reported from India. RNTCP has also focused on microlevel aspects, that is, newer diagnostics such as GenXpert, line probe assay and medicines such as bedaquiline for drug-resistant TB...
April 21, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28429168/bedaquiline-susceptibility-test-for-totally-drug-resistant-tuberculosis-mycobacterium-tuberculosis
#10
Ji-Chan Jang, Yong-Gyun Jung, Jungil Choi, Hyunju Jung, Sungweon Ryoo
This study aimed to provide information that bedaquilline is significantly effective for treatment of totally drug resistant (TDR) Mycobacterium tuberculosis that shows resistant to all first- and second-line drugs-using an innovative disc agarose channel (DAC) system. Time-lapse images of single bacterial cells under culture conditions with different concentrations of bedaquiline were analysed by image processing software to determine minimum inhibitory concentrations (MICs). Bedaquiline inhibited the growth of TDR M...
June 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28416555/mycobacterium-tuberculosis-proteome-response-to-anti-tuberculosis-compounds-reveals-metabolic-escape-pathways-that-prolong-bacterial-survival
#11
Lia Danelishvili, Natalia Shulzhenko, Jessica J J Chinison, Lmar Babrak, Jialu Hu, Andriy Morgun, Gregory Burrows, Luiz E Bermudez
Tuberculosis (TB) continues to be one of the most common bacterial infectious diseases and the leading cause of death in many parts of the world. A major limitation of TB therapy is slow killing of infecting organism, increasing the risk for the development of tolerance phenotype and drug-resistance. Studies indicate that M. tuberculosis (Mtb) takes several days to be killed upon treatment with lethal concentrations of antibiotics both in vitro and in vivo To investigate how metabolic remodeling can enable transient bacterial survival during exposure with bactericidal concentrations of compounds, Mtb H37Rv strain was exposed to twice of the minimal inhibitory concentration of isoniazid, rifampicin, moxifloxacin, mefloquine or bedaquiline for 24h, 48h, 4 days, and 6 days, and the bacterial proteomic response was analyzed using the quantitative shotgun mass spectrometry...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28400527/targeting-energy-metabolism-in-mycobacterium-tuberculosis-a-new-paradigm-in-antimycobacterial-drug-discovery
#12
REVIEW
Dirk Bald, Cristina Villellas, Ping Lu, Anil Koul
Drug-resistant mycobacterial infections are a serious global health challenge, leading to high mortality and socioeconomic burdens in developing countries worldwide. New innovative approaches, from identification of new targets to discovery of novel chemical scaffolds, are urgently needed. Recently, energy metabolism in mycobacteria, in particular the oxidative phosphorylation pathway, has emerged as an object of intense microbiological investigation and as a novel target pathway in drug discovery. New classes of antibacterials interfering with elements of the oxidative phosphorylation pathway are highly active in combating dormant or latent mycobacterial infections, with a promise of shortening tuberculosis chemotherapy...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28387862/examination-of-bedaquiline-and-linezolid-resistant-mycobacterium-tuberculosis-isolates-from-the-moscow-region
#13
Danila V Zimenkov, Elena Yu Nosova, Elena V Kulagina, Olga V Antonova, Liaisan R Arslanbaeva, Alexandra I Isakova, Ludmila Yu Krylova, Irina V Peretokina, Marina V Makarova, Svetlana G Safonova, Sergey E Borisov, Dmitry A Gryadunov
Objectives: To study the isolates with acquired resistance to bedaquiline and linezolid that were obtained from patients enrolled in a clinical study of a novel therapy regimen for drug-resistant TB in Moscow, Russia. Methods: Linezolid resistance was detected using MGIT 960 with a critical concentration of 1 mg/L. The MIC of bedaquiline was determined using the proportion method. To identify genetic determinants of resistance, sequencing of the mmpR ( Rv0678 ), atpE , atpC , pepQ , Rv1979c , rrl , rplC and rplD loci was performed...
April 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28361737/therapy-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis
#14
Barbara J Seaworth, David E Griffith
The global epidemic of multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin was recently reported as larger than previously estimated, with at least 580,000 new cases reported in 2015. Extensively drug-resistant tuberculosis (XDR-TB), MDR-TB with additional resistance to a second-line fluoroquinolone and injectable, continues to account for nearly 10% of MDR cases globally. Cases in India, China, and the Russian Federation account for >45% of the cases of MDR-TB...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#15
REVIEW
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis)...
March 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28331046/multidrug-resistant-tuberculosis-and-beyond-an-updated-analysis-of-the-current-evidence-on-bedaquiline
#16
EDITORIAL
Emanuele Pontali, Lia D'Ambrosio, Rosella Centis, Giovanni Sotgiu, Giovanni Battista Migliori
No abstract text is available yet for this article.
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28320727/primary-clofazimine-and-bedaquiline-resistance-among-isolates-from-patients-with-multidrug-resistant-tuberculosis
#17
Jian Xu, Bin Wang, Minghao Hu, Fengmin Huo, Shaochen Guo, Wei Jing, Eric Nuermberger, Yu Lu
Clofazimine has been repurposed for the treatment of tuberculosis, especially for multidrug-resistant tuberculosis (MDR-TB). To test the susceptibility to clofazimine of Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate alamarBlue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. For five clofazimine-resistant strains isolated from previously treated pre-extensively drug-resistant TB (pre-XDR-TB) and XDR-TB patients without prior exposure to clofazimine or bedaquiline, clofazimine MICs were ≥1...
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28270207/cost-effectiveness-of-adding-novel-or-group-5-interventions-to-a-background-regimen-for-the-treatment-of-multidrug-resistant-tuberculosis-in-germany
#18
Daniel Wirth, Ramesh Dass, Robert Hettle
BACKGROUND: Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective...
March 8, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28265350/cost-effectiveness-of-bedaquiline-in-mdr-and-xdr-tuberculosis-in-italy
#19
Luigi R Codecasa, Mondher Toumi, Anna D'Ausilio, Andrea Aiello, Francesco Damele, Roberta Termini, Alessia Uglietti, Robert Hettle, Giorgio Graziano, Saverio De Lorenzo
Objective: To evaluate the cost-effectiveness of bedaquiline plus background drug regimens (BR) for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in Italy. Methods: A Markov model was adapted to the Italian setting to estimate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR in the treatment of MDR-TB and XDR-TB over 10 years, from both the National Health Service (NHS) and societal perspective. Cost-effectiveness was evaluated in terms of life-years gained (LYG)...
2017: Journal of Market Access & Health Policy
https://www.readbyqxmd.com/read/28256383/the-challenge-of-the-new-tuberculosis-drugs
#20
REVIEW
Simon Tiberi, Ruaridh Buchanan, José A Caminero, Rosella Centis, Marcos Abdo Arbex, Miguel Salazar, Jessica Potter, Giovanni Battista Migliori
Tuberculosis (TB) continues to cause more deaths worldwide than any other single infectious disease. Even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. Since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regimen. This regimen is effective however it is pill burden, and duration has not received investment and innovation...
March 2017: La Presse Médicale
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