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https://www.readbyqxmd.com/read/29791557/new-and-repurposed-drugs-to-treat-multidrug-and-extensively-drug-resistant-tuberculosis
#1
Denise Rossato Silva, Margareth Dalcolmo, Simon Tiberi, Marcos Abdo Arbex, Marcela Munoz-Torrico, Raquel Duarte, Lia D'Ambrosio, Dina Visca, Adrian Rendon, Mina Gaga, Alimuddin Zumla, Giovanni Battista Migliori
Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources...
April 2018: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
https://www.readbyqxmd.com/read/29724920/delamanid-for-rifampicin-resistant-tuberculosis-a-retrospective-study-from-south-africa
#2
Erika Mohr, Jennifer Hughes, Anja Reuter, Laura Trivino Duran, Gabriella Ferlazzo, Johnny Daniels, Virginia De Avezedo, Yulene Kock, Sarah Jane Steele, Amir Shroufi, Serge Ade, Natavan Alikhanova, Guido Benedetti, Jeffrey Edwards, Helen Cox, Jennifer Furin, Petros Isaakidis
BACKGROUND: Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety from a programmatic setting in South Africa. METHODS: This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. Twelve-month interim outcomes, sputum culture conversion (SCC) by months-2 and 6, serious adverse events (SAEs), and QTcF data were reported...
May 3, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29701144/current-and-future-prospects-of-nitro-compounds-as-drugs-for-trypanosomiasis-and-leishmaniasis
#3
Alan H Fairlamb, Stephen Patterson
Interest in nitroheterocyclic drugs for the treatment of infectious diseases has undergone a resurgence in recent years. Here we review the current status of monocyclic and bicyclic nitroheterocyclic compounds as existing or potential new treatments for visceral leishmaniasis, Chagas' disease and human African trypanosomiasis. Both monocyclic (nifurtimox, benznidazole and fexinidazole) and bicyclic (pretomanid (PA-824) and delamanid (OPC-67683)) nitro-compounds are prodrugs, requiring enzymatic activation to exert their parasite toxicity...
April 26, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29665949/current-status-of-pharmacokinetic-and-safety-studies-of-multidrug-resistant-tuberculosis-treatment-in-children
#4
A J Garcia-Prats, E M Svensson, E D Weld, H S Schaaf, A C Hesseling
After decades of neglect, data are finally becoming available on the appropriate, safe dosing of key second-line anti-tuberculosis drugs used for treating multidrug-resistant tuberculosis (MDR-TB) in children, including levofloxacin (LVX), moxifloxacin (MFX), linezolid (LZD) and delamanid (DLM). Much needed data on some novel and repurposed drugs are still lacking, including for bedaquiline (BDQ), pretomanid (PTM) and clofazimine (CFZ). We review the status of pharmacokinetic (PK) and safety studies of key anti-tuberculosis medications in children with MDR-TB, identify priority knowledge gaps and note ongoing work to address those gaps, in the context of planning for an efficacy trial in children with MDR-TB...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29615346/corrigendum-to-mechanisms-of-resistance-to-delamanid-a-drug-for-mycobacterium-tuberculosis-tuberculosis-108-january-2018-186-194
#5
Mamoru Fujiwara, Masanori Kawasaki, Norimitsu Hariguchi, Yongge Liu, Makoto Matsumoto
No abstract text is available yet for this article.
March 31, 2018: Tuberculosis
https://www.readbyqxmd.com/read/29580819/tuberculosis-progress-and-advances-in-development-of-new-drugs-treatment-regimens-and-host-directed-therapies
#6
REVIEW
Simon Tiberi, Nelita du Plessis, Gerhard Walzl, Michael J Vjecha, Martin Rao, Francine Ntoumi, Sayoki Mfinanga, Nathan Kapata, Peter Mwaba, Timothy D McHugh, Giuseppe Ippolito, Giovanni Battista Migliori, Markus J Maeurer, Alimuddin Zumla
Tuberculosis remains the world's leading cause of death from an infectious disease, responsible for an estimated 1 674 000 deaths annually. WHO estimated 600 000 cases of rifampicin-resistant tuberculosis in 2016-of which 490 000 were multidrug resistant (MDR), with less than 50% survival after receiving recommended treatment regimens. Concerted efforts of stakeholders, advocates, and researchers are advancing further development of shorter course, more effective, safer, and better tolerated treatment regimens...
March 23, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29567722/will-regulatory-issues-continue-to-be-a-major-barrier-to-access-to-bedaquiline-and-delamanid
#7
EDITORIAL
Tiziana Masini, Janika Hauser, Rutendo Kuwana, Nguyen Nhat Linh, Ernesto Jaramillo
No abstract text is available yet for this article.
March 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29562988/global-programmatic-use-of-bedaquiline-and-delamanid-for-the-treatment-of-multidrug-resistant-tuberculosis
#8
V Cox, G Brigden, R H Crespo, E Lessem, S Lynch, M L Rich, B Waning, J Furin
SETTING: The World Health Organization recommended two new drugs, bedaquiline (BDQ) and delamanid (DLM), for the treatment of multidrug-resistant tuberculosis (MDR-TB) in 2013 and 2014, respectively. An estimated one third of patients with MDR-TB would benefit from the inclusion of these drugs in their treatment regimens. DESIGN: A convenience sample of 36 countries voluntarily reported monthly data on cumulative programmatic use of new drugs to the Drug-Resistant TB Scale-Up Treatment Action Team between 1 July 2015 and 31 June 2017...
April 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29559119/evaluation-of-nitroxyl-donors-effect-on-mycobacteria
#9
Jordana Galizia, Mariano Prado Acosta, Estefanía Urdániz, Marcelo A Martí, Mariana Piuri
Nitroxyl (HNO) is a highly elusive and reactive molecule. Nitroxyl biological effects and pharmacological potential are becoming increasingly relevant. Mycobacterium tuberculosis infection needs new and more efficient drugs. Reactive Nitrogen and Oxygen Species (RNOS) are key compounds used by the immune system to fight intracellular infections, particularly Mycobacterium tuberculosis. In this context, we analyzed HNO potential to kill mycobacteria. We evaluated the viability and biological response of mycobacteria towards HNO releasing compounds...
March 2018: Tuberculosis
https://www.readbyqxmd.com/read/29549838/drug-discovery-in-tuberculosis-new-drug-targets-and-antimycobacterial-agents
#10
REVIEW
André Campaniço, Rui Moreira, Francisca Lopes
Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy...
April 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29545276/bedaquiline-and-delamanid-for-the-treatment-of-multidrug-resistant-tuberculosis-a-multicentre-cohort-study-in-korea
#11
Cheon Tae Kim, Tae-Ok Kim, Hong-Joon Shin, Young Chun Ko, Yeong Hun Choe, Hak-Ryul Kim, Yong-Soo Kwon
Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment.This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11) or both, either sequentially (n=10) or in coadministration (n=1), for >1 month, combined with a World Health Organization-recommended regimen.Of these, 49 (80.3%) were male and 12 (19.7%) were female. The median (interquartile range (IQR)) age was 53 (38...
March 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29544148/recent-advances-of-imidazole-containing-derivatives-as-anti-tubercular-agents
#12
REVIEW
Yi-Lei Fan, Xiao-Hong Jin, Zhong-Ping Huang, Hai-Feng Yu, Zhi-Gang Zeng, Tao Gao, Lian-Shun Feng
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity...
April 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29523322/mechanisms-of-resistance-to-delamanid-a-drug-for-mycobacterium-tuberculosis
#13
Mamoru Fujiwara, Masanori Kawasaki, Norimitsu Hariguchi, Yongge Liu, Makoto Matsumoto
Delamanid, a bicyclic nitroimidazooxazole, is effective against M. tuberculosis. Previous studies have shown that resistance to a bicyclic nitroimidazooxazine, PA-824, is caused by mutations in an F420 -dependent bio-activation pathway. We investigated whether the same mechanisms are responsible for resistance to delamanid. Spontaneous resistance frequencies were determined using M. bovis BCG Tokyo (BCG) and M. tuberculosis H37Rv. F420 high-performance liquid chromatography (HPLC) elution patterns of homogenates of delamanid-resistant BCG colonies and two previously identified delamanid-resistant M...
January 2018: Tuberculosis
https://www.readbyqxmd.com/read/29487031/new-drugs-and-perspectives-for-new-anti-tuberculosis-regimens
#14
S Tiberi, M Muñoz-Torrico, R Duarte, M Dalcolmo, L D'Ambrosio, G-B Migliori
Tuberculosis (TB) is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required. Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested...
March 2018: Pulmonology
https://www.readbyqxmd.com/read/29470252/multi-and-extensively-drug-resistant-pulmonary-tuberculosis-advances-in-diagnosis-and-management
#15
Emanuele Pontali, Dina Visca, Rosella Centis, Lia D'Ambrosio, Antonio Spanevello, Giovanni Battista Migliori
PURPOSE OF REVIEW: Multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR)-TB epidemics are key obstacles towards TB control and elimination. RECENT FINDINGS: Diagnosis of MDR/XDR-TB is difficult and requires several weeks. New diagnostic tools are being tested and proposed allowing for shorter time to diagnosis and reduced delays in starting an adequate treatment regimen. MDR/XDR-TB treatment strategies are currently on an evolving stage...
May 2018: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29452942/early-safety-and-efficacy-of-the-combination-of-bedaquiline-and-delamanid-for-the-treatment-of-patients-with-drug-resistant-tuberculosis-in-armenia-india-and-south-africa-a-retrospective-cohort-study
#16
Gabriella Ferlazzo, Erika Mohr, Chinmay Laxmeshwar, Catherine Hewison, Jennifer Hughes, Sylvie Jonckheere, Naira Khachatryan, Virginia De Avezedo, Lusine Egazaryan, Amir Shroufi, Stobdan Kalon, Helen Cox, Jennifer Furin, Petros Isaakidis
BACKGROUND: Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa...
May 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29452940/combining-bedaquiline-and-delamanid-to-treat-multidrug-resistant-tuberculosis
#17
Marina Tadolini, Simon Tiberi, Giovanni Battista Migliori
No abstract text is available yet for this article.
May 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29412643/the-expanding-diversity-of-mycobacterium-tuberculosis-drug-targets
#18
Samantha Wellington, Deborah T Hung
After decades of relative inactivity, a large increase in efforts to discover antitubercular therapeutics has brought insights into the biology of Mycobacterium tuberculosis (Mtb) and promising new drugs such as bedaquiline, which inhibits ATP synthase, and the nitroimidazoles delamanid and pretomanid, which inhibit both mycolic acid synthesis and energy production. Despite these advances, the drug discovery pipeline remains underpopulated. The field desperately needs compounds with novel mechanisms of action capable of inhibiting multi- and extensively drug -resistant Mtb (M/XDR-TB) and, potentially, nonreplicating Mtb with the hope of shortening the duration of required therapy...
February 15, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29346118/mycobacterium-avium-complex-pulmonary-disease-new-epidemiology-and-management-concepts
#19
Leah Lande, Jason George, Theodore Plush
PURPOSE OF REVIEW: The prevalence of Mycobacterium avium complex (MAC)-related pulmonary disease has been increasing because of environmental factors, changes in organism virulence, and evolving host susceptibility. Treatment is often complicated by adverse effects, development of drug resistance, and refractory disease, with recurrence rates as high as 25-45%. RECENT FINDINGS: Aerosolization of water, soil, or dusts are the likely sources of MAC-related pulmonary disease in susceptible individuals...
April 2018: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29297439/world-health-organization-recommendations-for-multidrug-resistant-tuberculosis-should-different-standards-be-applied
#20
V Cox, J Furin
The World Health Organization uses a Grading of Recommendations Assessment, Development, and Evaluation process to make recommendations for treating multidrug-resistant tuberculosis. Even with this standardized approach, there have been discrepancies between recommendations for newer drugs such as bedaquiline and delamanid and the shorter regimen. This may be because newer drugs are novel chemical entities and may merit closer scrutiny. Here, we explore the problematic nature of this supposition, arguing that although the newer drugs have been used in fewer individuals, they may have more robust efficacy and safety data than many of the second-line drugs used in the shorter regimen...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
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