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https://www.readbyqxmd.com/read/28432172/why-tuberculosis-control-programmes-fail-role-of-microlevel-and-macrolevel-factors-an-analysis-from-india
#1
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
#2
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...
April 20, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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 MDR-TB. To test the susceptibility to clofazimine for Mycobacterium tuberculosis clinical isolates, MICs of clofazimine were determined using the microplate Alamar blue assay (MABA) method for 80 drug-resistant isolates and 10 drug-susceptible isolates for comparison. Five clofazimine-resistant strains isolated from previously treated pre-XDR and XDR-TB patients without prior exposure to clofazimine or bedaquiline had clofazimine MICs ≥1...
March 20, 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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28256380/the-cursed-duet-today-tuberculosis-and-hiv-coinfection
#13
REVIEW
Simon Tiberi, Anna Cristina C Carvalho, Giorgia Sulis, Devan Vaghela, Adrian Rendon, Fernanda C de Q Mello, Ananna Rahman, Nashaba Matin, Ali Zumla, Emanuele Pontali
The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed...
March 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28242674/in-vitro-activity-of-bedaquiline-against-nontuberculous-mycobacteria-in-china
#14
Yu Pang, Huiwen Zheng, Yaoju Tan, Yuanyuan Song, Yanlin Zhao
The main goal of our study was to evaluate in vitro drug susceptibility of bedaquiline against six prevalent pathogenic nontuberculous mycobacteria (NTM) diseases in China. In addition, we investigated the potential molecular mechanism contributing to the bedaquiline resistance in these different NTM species. For slowly growing mycobacteria (SGM), bedaquiline exhibited the highest activity against Mycobacterium avium, the MIC50 and MIC90 were 0.03 and 16 mg/L, respectively. Of rapidly growing mycobacteria (RGM), Mycobacterium abscessus subsp...
February 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28240569/selected-questions-and-controversies-about-bedaquiline-a-view-from-the-field
#15
K Dheda, A Esmail, J Limberis, G Maartens
Although there has been a slow decline in tuberculosis (TB) incidence worldwide, the prevalence of drug-resistant TB in most high-burden countries has increased. Drug-resistant TB is associated with high mortality, is a threat to health care workers in TB-endemic countries and is prohibitively costly, which diverts resources away from drug-susceptible cases. Amplification of resistance means that there is an increasing proportion of patients with multidrug-resistant TB who have extensively drug-resistant TB (XDR-TB) or are programmatically untreatable...
December 1, 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28240568/-re-moving-the-needle-prospects-for-all-oral-treatment-for-multidrug-resistant-tuberculosis
#16
M Milstein, A Brzezinski, F Varaine, C D Mitnick
BACKGROUND: Currently recommended regimens for multidrug-resistant tuberculosis (MDR-TB) contain painful daily injections and are unsuccessful in approximately half of patients. Removal of the injectable agent to fashion all-oral regimens could transform MDR-TB treatment and access to care. OBJECTIVE: To explore evidence for all-oral treatment regimens. DESIGN: We review evidence on drugs that could be included in injection-free MDR-TB regimens...
December 1, 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28196957/a-novel-small-molecule-inhibitor-of-the-mycobacterium-tuberculosis-demethylmenaquinone-methyltransferase-meng-is-bactericidal-to-both-growing-and-nutritionally-deprived-persister-cells
#17
Paridhi Sukheja, Pradeep Kumar, Nisha Mittal, Shao-Gang Li, Eric Singleton, Riccardo Russo, Alexander L Perryman, Riju Shrestha, Divya Awasthi, Seema Husain, Patricia Soteropoulos, Roman Brukh, Nancy Connell, Joel S Freundlich, David Alland
Active tuberculosis (TB) and latent Mycobacterium tuberculosis infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating M. tuberculosis "persisters" that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent M. tuberculosis and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28182570/long-term-outcome-and-safety-of-prolonged-bedaquiline-treatment-for-multidrug-resistant-tuberculosis
#18
Lorenzo Guglielmetti, Marie Jaspard, Damien Le Dû, Marie Lachâtre, Dhiba Marigot-Outtandy, Christine Bernard, Nicolas Veziris, Jérôme Robert, Yazdan Yazdanpanah, Eric Caumes, Mathilde Fréchet-Jachym
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes...
December 22, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28178199/combined-use-of-delamanid-and-bedaquiline-to-treat-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-a-systematic-review
#19
REVIEW
Giovanni Battista Migliori, Emanuele Pontali, Giovanni Sotgiu, Rosella Centis, Lia D'Ambrosio, Simon Tiberi, Marina Tadolini, Susanna Esposito
The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28169199/landmark-legal-ruling-sees-indian-girl-prescribed-bedaquiline-for-xdr-tb
#20
Tony Kirby
No abstract text is available yet for this article.
February 3, 2017: Lancet Respiratory Medicine
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