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https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#1
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/28331043/world-health-organization-treatment-guidelines-for-drug-resistant-tuberculosis-2016-update
#2
Dennis Falzon, Holger J Schünemann, Elizabeth Harausz, Licé González-Angulo, Christian Lienhardt, Ernesto Jaramillo, Karin Weyer
Antimicrobial resistance is a major global concern. Tuberculosis (TB) strains resistant to rifampicin and other TB medicines challenge patient survival and public health. The World Health Organization (WHO) has published treatment guidelines for drug-resistant TB since 1997 and last updated them in 2016 based on reviews of aggregated and individual patient data from published and unpublished studies. An international expert panel formulated recommendations following the GRADE approach. The new WHO guidelines recommend a standardised 9-12 months shorter treatment regimen as first choice in patients with multidrug- or rifampicin-resistant TB (MDR/RR-TB) strains not resistant to fluoroquinolones or second-line injectable agents; resistance to these two classes of core second-line medicines is rapidly detectable with molecular diagnostics also approved by WHO in 2016...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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
#3
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/28256383/the-challenge-of-the-new-tuberculosis-drugs
#4
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...
February 27, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28256380/the-cursed-duet-today-tuberculosis-and-hiv-coinfection
#5
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...
February 27, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28240570/delamanid-in-the-treatment-of-multidrug-resistant-tuberculosis
#6
R Gupta, C D Wells, N Hittel, J Hafkin, L J Geiter
Otsuka has been engaged in anti-tuberculosis drug development efforts for over 30 years, and is the leading private sector funder of tuberculosis (TB) research and development. Delamanid (DLM), discovered by Otsuka's scientists, has been shown to provide benefit with respect to short-term surrogate markers and long-term treatment outcomes, and it has received regulatory approval for treatment of adult pulmonary multidrug-resistant TB (MDR-TB) as one of only two new anti-tuberculosis drugs in the last 40 years...
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
#7
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/28178199/combined-use-of-delamanid-and-bedaquiline-to-treat-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-a-systematic-review
#8
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/28109869/outcomes-infectiousness-and-transmission-dynamics-of-patients-with-extensively-drug-resistant-tuberculosis-and-home-discharged-patients-with-programmatically-incurable-tuberculosis-a-prospective-cohort-study
#9
Keertan Dheda, Jason D Limberis, Elize Pietersen, Jody Phelan, Aliasgar Esmail, Maia Lesosky, Kevin P Fennelly, Julian Te Riele, Barbara Mastrapa, Elizabeth M Streicher, Tania Dolby, Abdallah M Abdallah, Fathia Ben-Rached, John Simpson, Liezel Smith, Tawanda Gumbo, Paul van Helden, Frederick A Sirgel, Ruth McNerney, Grant Theron, Arnab Pain, Taane G Clark, Robin M Warren
BACKGROUND: The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies. METHODS: In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179)...
January 18, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28092695/absorption-distribution-and-excretion-of-the-anti-tuberculosis-drug-delamanid-in-rats-extensive-tissue-distribution-suggests-potential-therapeutic-value-for-extrapulmonary-tuberculosis
#10
Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara
Delamanid (OPC-67683, Deltyba(TM) , nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution, and excretion of delamanid-derived radioactivity were investigated after a single oral administration of (14) C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 hours postdose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma...
January 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28073970/estimated-generic-prices-for-novel-treatments-for-drug-resistant-tuberculosis
#11
Dzintars Gotham, Joseph Fortunak, Anton Pozniak, Saye Khoo, Graham Cooke, Frederick E Nytko, Andrew Hill
BACKGROUND: The estimated worldwide annual incidence of MDR-TB is 480 000, representing 5% of TB incidence, but 20% of mortality. Multiple drugs have recently been developed or repurposed for the treatment of MDR-TB. Currently, treatment for MDR-TB costs thousands of dollars per course. OBJECTIVES: To estimate generic prices for novel TB drugs that would be achievable given large-scale competitive manufacture. METHODS: Prices for linezolid, moxifloxacin and clofazimine were estimated based on per-kilogram prices of the active pharmaceutical ingredient (API)...
January 10, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28043603/individualized-treatment-of-multidrug-resistant-tuberculosis-using-therapeutic-drug-monitoring
#12
Mathieu S Bolhuis, Onno W Akkerman, Marieke G G Sturkenboom, Wiel C M de Lange, Tjip S van der Werf, Jan-Willem C Alffenaar
OBJECTIVE/BACKGROUND: Globally, approximately 50% of patients with multidrug-resistant tuberculosis (MDR-TB) experience treatment failure. MDR-TB treatment is hindered by adverse events, toxicity of the second-line anti-TB drugs, logistics and costs, especially in low-income countries, and problems with medication adherence. Pharmacokinetic variability is also attributed as one of the reasons contributing to treatment failure. In our reference Tuberculosis Center Beatrixoord (University Medical Center Groningen, Groningen, The Netherlands), we strive to individualize treatment of all MDR-TB patients based on drug-susceptibility testing using minimal inhibitory concentrations and pharmacokinetic parameters...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27994440/use-of-bedaquiline-and-delamanid-in-diabetes-patients-clinical-and-pharmacological-considerations
#13
REVIEW
Minhui Hu, Chunlan Zheng, Feng Gao
Antituberculosis (anti-TB) treatment may be affected by both diabetes and hypoglycemic agents in patients with these 2 comorbidities. However, data supporting this conclusion relate only to standard anti-TB therapies. Sirturo(®) (bedaquiline) and Deltyba(®) (delamanid), novel drugs for multidrug-resistant tuberculosis (MDR-TB), are recommended for diabetes patients when another effective treatment regimen cannot be provided. Currently, there are no clinical data related to the use of these agents in diabetes patients...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27988333/delamanid-is-not-metabolized-by-salmonella-or-human-nitroreductases-a-possible-mechanism-for-the-lack-of-mutagenicity
#14
COMPARATIVE STUDY
Erina Hanaki, Mikayo Hayashi, Makoto Matsumoto
Nitro-containing compounds such as nitrofuran and nitroimidazole are drugs used for the treatment of infectious diseases. However, many of these nitro-containing drugs are positive in the bacterial reverse mutation assay (Ames test). The recently approved anti-multidrug-resistant tuberculosis (MDR-TB) drug, delamanid (Deltyba™; OPC-67683), a derivative of 4-nitroimidazole, was negative for mutagenicity in the Ames assay. In Salmonella typhimurium, mutagenicity of nitro compounds has been closely associated with the ability of nitroreductase to metabolize (degradation)these compounds...
March 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/27966048/discovery-and-characterization-of-an-f420-dependent-glucose-6-phosphate-dehydrogenase-rh-fgd1-from-rhodococcus-jostii-rha1
#15
Quoc-Thai Nguyen, Gianluca Trinco, Claudia Binda, Andrea Mattevi, Marco W Fraaije
Cofactor F420, a 5-deazaflavin involved in obligatory hydride transfer, is widely distributed among archaeal methanogens and actinomycetes. Owing to the low redox potential of the cofactor, F420-dependent enzymes play a pivotal role in central catabolic pathways and xenobiotic degradation processes in these organisms. A physiologically essential deazaflavoenzyme is the F420-dependent glucose-6-phosphate dehydrogenase (FGD), which catalyzes the reaction F420 + glucose-6-phosphate → F420H2 + 6-phospho-gluconolactone...
December 13, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27906009/current-trends-and-intricacies-in-the-management-of-hiv-associated-pulmonary-tuberculosis
#16
REVIEW
Narendran Gopalan, Padmapriyadarsini Chandrasekaran, Soumya Swaminathan, Srikanth Tripathy
Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy...
September 26, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27861363/efficacy-safety-and-tolerability-of-a-24-month-treatment-regimen-including-delamanid-in-a-child-with-extensively-drug-resistant-tuberculosis-a-case-report-and-review-of-the-literature
#17
REVIEW
Susanna Esposito, Samantha Bosis, Marina Tadolini, Sonia Bianchini, Giovanni Battista Migliori, Nicola Principi
RATIONAL: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are emerging problems in several countries. These infections require long and expensive treatment regimens. Recently, 2 new drugs, bedaquiline and delamanid, have been approved in several countries for use in adults with severe, difficult-to-treat MDR-TB, and it has been suggested that they could also be administered to children with MDR-TB and limited treatment options. However, no study has been completed on their efficacy...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27854508/new-repurposed-drugs-for-pediatric-multidrug-resistant-tuberculosis-practice-based-recommendations
#18
Elizabeth P Harausz, Anthony J Garcia-Prats, James A Seddon, H Simon Schaaf, Anneke C Hesseling, Jay Achar, Jonathan Bernheimer, Andrea Cruz, Lia D'Ambrosio, Anne Detjen, Stephen M Graham, Jennifer Hughes, Sylvie Jonckheere, Ben J Marais, Giovanni Battista Migliori, Lindsay McKenna, Alena Skrahina, Marina Tadolini, Peyton Wilson, Jennifer Furin
It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents...
November 17, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27816662/applicability-of-the-shorter-bangladesh-regimen-in-high-multidrug-resistant-tuberculosis-settings
#19
Giovanni Sotgiu, Simon Tiberi, Rosella Centis, Lia D'Ambrosio, Zhenia Fuentes, Alimuddin Zumla, Giovanni Battista Migliori
In spite of the recent introduction of two new drugs (delamanid and bedaquiline) and a few repurposed compounds to treat multidrug-resistant and extensively drug-resistant tuberculosis (MDR- and XDR-TB), clinicians are facing increasing problems in designing effective regimens in severe cases. Recently a 9 to 12-month regimen (known as the 'Bangladesh regimen') proved to be effective in treating MDR-TB cases. It included an initial phase of 4 to 6 months of kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol, followed by 5 months of moxifloxacin, clofazimine, pyrazinamide, and ethambutol...
November 2, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27812217/activation-of-bicyclic-nitro-drugs-by-a-novel-nitroreductase-ntr2-in-leishmania
#20
Susan Wyllie, Adam J Roberts, Suzanne Norval, Stephen Patterson, Bernardo J Foth, Matthew Berriman, Kevin D Read, Alan H Fairlamb
Drug discovery pipelines for the "neglected diseases" are now heavily populated with nitroheterocyclic compounds. Recently, the bicyclic nitro-compounds (R)-PA-824, DNDI-VL-2098 and delamanid have been identified as potential candidates for the treatment of visceral leishmaniasis. Using a combination of quantitative proteomics and whole genome sequencing of susceptible and drug-resistant parasites we identified a putative NAD(P)H oxidase as the activating nitroreductase (NTR2). Whole genome sequencing revealed that deletion of a single cytosine in the gene for NTR2 that is likely to result in the expression of a non-functional truncated protein...
November 2016: PLoS Pathogens
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