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https://www.readbyqxmd.com/read/27906009/current-trends-and-intricacies-in-the-management-of-hiv-associated-pulmonary-tuberculosis
#1
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
#2
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
#3
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-mdr-tb-settings
#4
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 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
#5
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
https://www.readbyqxmd.com/read/27798206/screening-of-anti-mycobacterial-compounds-in-a-naturally-infected-zebrafish-larvae-model
#6
J P Dalton, B Uy, K S Okuda, C J Hall, W A Denny, P S Crosier, S Swift, S Wiles
OBJECTIVES: Mycobacterium tuberculosis is a deadly human pathogen that causes the lung disease TB. M. tuberculosis latently infects a third of the world's population, resulting in ∼1.5 million deaths per year. Due to the difficulties and expense of carrying out animal drug trials using M. tuberculosis and rodents, infections of the zebrafish Danio rerio with Mycobacterium marinum have become a useful surrogate. However, the infection methods described to date require specialized equipment and a high level of operator expertise...
October 24, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27797620/reply-call-for-regular-susceptibility-testing-of-bedaquiline-and-delamanid
#7
Harald Hoffmann, Sabine Hofmann-Thiel, Matthias Merker, Thomas A Kohl, Stefan Niemann
No abstract text is available yet for this article.
November 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27797614/preventing-acquired-resistance-to-bedaquiline-and-delamanid-in-multidrug-resistant-tuberculosis-treatment-requires-optimal-management
#8
Lorenzo Guglielmetti, Damien Le Dû, Mathilde Fréchet-Jachym, Carole Mitnick
No abstract text is available yet for this article.
November 1, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27762157/individualizing-management-of-extensively-drug-resistant-tuberculosis-diagnostics-treatment-and-biomarkers
#9
Jan-Willem Alffenaar, Onno W Akkerman, Richard Anthony, Simon Tiberi, Scott Heysell, M P Grobusch, Frank Cobelens, Dick van Soolingen
Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M...
October 20, 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27756712/clinical-management-of-adults-and-children-with-mdr-and-xdr-tb
#10
REVIEW
Keertan Dheda, Kwok Chiu Chang, Lorenzo Guglielmetti, Jennifer Furin, H Simon Schaaf, Dumitru Chesov, Aliasgar Esmail, Christoph Lange
Globally there is a burgeoning epidemic of drug mono-resistant tuberculosis (TB), multi-drug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least 1 major TB drug including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycocide. This trend cannot be ignored because DR-TB is associated with greater morbidity compared to drug-sensitive TB, it accounts for almost 25% of global TB mortality, is extremely costly to treat, consuming substantial portions of budgets allocated to national TB programmes in TB endemic countries, and is a major threat to healthcare workers who are already in short supply in resource-poor settings...
October 15, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27725032/using-bedaquiline-and-delamanid-in-combination-and-safely
#11
Martin Dedicoat
No abstract text is available yet for this article.
October 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/27708678/current-trends-and-intricacies-in-the-management-of-hiv-associated-pulmonary-tuberculosis
#12
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...
2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27695682/the-experience-of-bedaquiline-implementation-at-a-decentralised-clinic-in-south-africa
#13
R Cariem, V Cox, V de Azevedo, J Hughes, E Mohr, L Triviño Durán, N Ndjeka, J Furin
Multidrug-resistant tuberculosis (MDR-TB) is a serious public health problem, but the new drugs bedaquiline (BDQ) and delamanid offer hope to improve outcomes and minimise toxicity. In Khayelitsha, South Africa, patients are routinely started on BDQ in the out-patient setting. This report from the field describes BDQ use in the out-patient setting at the Nolungile Clinic. The clinic staff overall report a positive experience using the drug. Challenges have been based largely on the logistics of drug supply and delivery...
September 2016: Public Health Action
https://www.readbyqxmd.com/read/27678056/repurposing-clinically-approved-cephalosporins-for-tuberculosis-therapy
#14
Santiago Ramón-García, Rubén González Del Río, Angel Santos Villarejo, Gaye D Sweet, Fraser Cunningham, David Barros, Lluís Ballell, Alfonso Mendoza-Losana, Santiago Ferrer-Bazaga, Charles J Thompson
While modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy, and ethambutol, a first-line anti-TB drug...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27672155/inhibiting-mycobacterium-tuberculosis-within-and-without
#15
REVIEW
Stewart T Cole
Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials...
November 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27637852/multidrug-and-extensively-drug-resistant-tuberculosis
#16
T Maitre, A Aubry, V Jarlier, J Robert, N Veziris
The emergence of drug-resistant tuberculosis (TB) compromises global tuberculosis control. The incidence of multidrug-resistant strains (MDR) defined as resistant to the two main antituberculosis drugs, rifampicin and isoniazid, was raised in the 1990s. Ten percent of these strains have developed additional resistance to the main second-line antituberculosis drugs: fluoroquinolones and aminoglycosides. These strains are defined as extensively drug-resistant (XDR). The prognosis of MDR-TB and XDR-TB is poor due to limited therapeutic resources...
September 13, 2016: Médecine et Maladies Infectieuses
https://www.readbyqxmd.com/read/27550243/antibiotic-stewardship-for-drug-resistant-tuberculosis
#17
Nesri Padayatchi, Sharana Mahomed, Marian Loveday, Kogieleum Naidoo
No abstract text is available yet for this article.
October 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27465204/comparison-of-effectiveness-between-delamanid-and-bedaquiline-among-patients-with-multidrug-resistant-tuberculosis-a-markov-model-simulation-study
#18
Ji-Hye Byun, Jae-A Park, Hye-Rim Kang, Ju-Young Shin, Eui-Kyung Lee
BACKGROUND: No clear evidence on the comparative effectiveness of delamanid (DLM) and bedaquiline (BDQ) has been published. OBJECTIVE: This study aims to estimate the incremental effectiveness of DLM versus BDQ in patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: We developed a Markov model based on a cohort with MDR-TB, which consisted of success, failure, loss to follow-up, and death. The cohort simulation was conducted assuming each patient was 36 years old and, lived until age 82, and that the cycle length was 1 year...
November 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27458876/adverse-effects-of-oral-second-line-antituberculosis-drugs-in-children
#19
H Simon Schaaf, Stephanie Thee, Louvina van der Laan, Anneke C Hesseling, Anthony J Garcia-Prats
INTRODUCTION: Increasing numbers of children with drug-resistant tuberculosis are accessing second-line antituberculosis drugs; these are more toxic than first-line drugs. Little is known about the safety of new antituberculosis drugs in children. Knowledge of adverse effects, and how to assess and manage these, is important to ensure good adherence and treatment outcomes. AREAS COVERED: A Pubmed search was performed to identify articles addressing adverse effects of second-line antituberculosis drugs; a general search was done for the new drugs delamanid and bedaquiline...
October 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27458223/delamanid-coadministered-with-antiretroviral-drugs-or-antituberculosis-drugs-shows-no-clinically-relevant-drug-drug-interactions-in-healthy-subjects
#20
Suresh Mallikaarjun, Charles Wells, Carolyn Petersen, Anne Paccaly, Susan E Shoaf, Shiva Patil, Lawrence Geiter
Delamanid is a medicinal product approved for treatment of multidrug-resistant tuberculosis. Three studies were conducted to evaluate the potential drug-drug interactions between delamanid and antiretroviral drugs, including ritonavir, a strong inhibitor of CYP3A4, and selected anti-TB drugs, including rifampin, a strong inducer of cytochrome P450 (CYP) isozymes. Multiple-dose studies were conducted in parallel groups of healthy subjects. Plasma samples were analyzed for delamanid, delamanid metabolite, and coadministered drug concentrations, and pharmacokinetic (PK) parameters were determined...
October 2016: Antimicrobial Agents and Chemotherapy
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