keyword
MENU ▼
Read by QxMD icon Read
search

Bedaquiline

keyword
https://www.readbyqxmd.com/read/29146605/cardiac-safety-of-bedaquiline-a-systematic-and-critical-analysis-of-the-evidence
#1
EDITORIAL
Emanuele Pontali, Giovanni Sotgiu, Simon Tiberi, Lia D'Ambrosio, Rosella Centis, Giovanni B Migliori
No abstract text is available yet for this article.
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29145924/pharmacokinetic-interaction-between-bedaquiline-and-clofazimine-in-patients-with-drug-resistant-tuberculosis
#2
G Maartens, M J E Brill, M Pandie, E M Svensson
<h2>BACKGROUND:</h2>Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ.<h2>METHODS:</h2>We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB...
November 16, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29133206/relationship-between-polarities-of-antibiotic-and-polymer-matrix-on-nanoparticle-formulations-based-on-aliphatic-polyesters
#3
J A S Ritsema, E M A Herschberg, S E Borgos, C Løvmo, R Schmid, Y M Te Welscher, G Storm, C F van Nostrum
In the field of nanomedicine, nanoparticles are developed to target antibiotics to sites of bacterial infection thus enabling adequate drug exposure and decrease development of resistant bacteria. In the present study, we investigated the encapsulation of two antibiotics with different polarity into different PEGylated polymeric nanoparticles based on aliphatic polyesters, to obtain a better understanding of critical factors determining encapsulation and release. The nanoparticles were prepared from diblock copolymers comprising of a poly(ethylene glycol) block attached to an aliphatic polyester block of varying polarity: poly(lactic-co-glycolic acid) (mPEG-PLGA), poly(lactic-co-hydroxymethyl glycolic acid) (mPEG-PLHMGA) and poly(lactic-co-benzyloxymethyl glycolic acid) (mPEG-PLBMGA)...
November 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29130630/a-structure-based-strategy-toward-the-development-of-novel-candidates-for-antimycobacterial-activity-synthesis-biological-evaluation-and-docking-study
#4
Linhu Li, Yuanyuan Jin, Bin Wang, Zhaoyong Yang, Mingliang Liu, Huiyuan Guo, Jun Zhang, Yu Lu
Bacterial resistance to most of the available antibiotics has stimulated the discovery of novel efficacious antibacterial agents. Bedaquiline is first of its type that has been specifically introduced for the management of MDR-TB in combination with other drugs. In the current study, a series of isoniazid/ethambutol/pyrazinamide -quinoline conjugates based on the structures of Bedaquiline were designed and synthesized. Biological activity tests revealed that some of isoniazid/ethambutol-quinoline conjugates have useful antibiotic activity against MTB H37Rv (MIC: 2...
November 11, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29126225/bedaquiline-resistance-its-emergence-mechanism-and-prevention
#5
Thi Van Anh Nguyen, Richard M Anthony, Anne-Laure Bañuls, Dinh Hoa Vu, Jan-Willem C Alffenaar
Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance...
November 8, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29107691/antibiotic-bedaquiline-effectively-targets-growth-survival-and-tumor-angiogenesis-of-lung-cancer-through-suppressing-energy-metabolism
#6
Xiaomu Wu, Fajiu Li, Xiaojiang Wang, Chenghong Li, Qinghua Meng, Chuanhai Wang, Jie Huang, Shi Chen, Ziyang Zhu
Tumor angiogenesis plays essential roles during lung cancer progression and metastasis. Therapeutic agent that targets both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy. We demonstrate that bedaquiline, a FDA-approved antibiotic drug, effectively targets lung cancer cells and angiogenesis. Bedaquiline dose-dependently inhibits proliferation and induces apoptosis of a panel of lung cancer cell lines regardless of subtypes and molecular heterogeneity. Bedaquiline also inhibits capillary network formation of human lung tumor associated-endothelial cell (HLT-EC) on Matrigel and its multiple functions, such as spreading, proliferation and apoptosis, even in the presence of vascular endothelial growth factor (VEGF)...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29107541/synthesis-and-evaluation-of-analogues-of-the-tuberculosis-drug-bedaquiline-containing-heterocyclic-b-ring-units
#7
Peter J Choi, Hamish S Sutherland, Amy S T Tong, Adrian Blaser, Scott G Franzblau, Christopher B Cooper, Manisha U Lotlikar, Anna M Upton, Jerome Guillemont, Magali Motte, Laurence Queguiner, Koen Andries, Walter Van den Broeck, William A Denny, Brian D Palmer
Analogues of bedaquiline where the phenyl B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesised and evaluated. While there was an expected broad positive correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an additional contribution to antibacterial potency. The majority of the compounds were (desirably) more polar and had higher rates of clearance than bedaquiline, and showed acceptable oral bioavailability, but there was only limited (and unpredictable) improvement in their hERG liability...
October 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29066216/performance-of-the-genotype-mtbdrsl-assay-for-the-detection-second-line-anti-tuberculosis-drug-resistance
#8
Young Seok Lee, Bo Young Lee, Kyung-Wook Jo, Tae Sun Shim
The rapid detection of drug-resistant tuberculosis (TB) is important to improve treatment outcomes and prevent disease transmission. The GenoType MTBDRsl assay (MTBDRsl assay) was developed to detect fluoroquinolone (FQ) and second-line injectable drug (SLID) resistance. The aim of this study was to evaluate the performance and clinical utility of MTBDRsl assay. We retrospectively reviewed patient medical records with MTBDRsl assay data between December 2011 and February 2017. MTBDRsl assay results were compared with that of phenotypic drug susceptibility testing...
October 20, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29061760/combinations-of-respiratory-chain-inhibitors-have-enhanced-bactericidal-activity-against-mycobacterium-tuberculosis
#9
Bryan J Berube, Tanya Parish
As an obligate aerobe Mycobacterium tuberculosis uses its electron-transport chain (ETC) to produce energy via oxidative phosphorylation. This pathway has recently garnered a lot of attention and is a target for several new anti-mycobacterials. We tested the respiratory adaptation of M. tuberculosis to phenoxy alkyl benzimidazoles (PABs), compounds proposed to target QcrB, a component of the cytochrome bc1 complex. We show M. tuberculosis is able to reroute its ETC to provide temporary resistance to PABs. However, combination treatment of PAB with agents targeting other components of the electron-transport chain overcomes this respiratory flexibility...
October 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29061739/impact-of-rifabutin-or-rifampin-on-bedaquiline-safety-tolerability-and-pharmacokinetics-a-randomized-clinical-trial-in-healthy-adult-volunteers
#10
Amanda M Healan, J McLeod Griffiss, Howard M Proskin, Mary Ann O'Riordan, Wesley A Gray, Robert A Salata, Jeffrey L Blumer
Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial adenosine triphosphate synthase. Bedaquiline has effectively treated disease caused by susceptible and drug-resistant Mycobacterium tuberculosis (TB). Rifamycins are a cornerstone of combination drug regimens for the treatment of TB. This Phase 1, open label, randomized, controlled trial evaluated the effect of steady-state dosing of rifabutin or rifampin on the safety, tolerability, and pharmacokinetics of bedaquiline given as a single dose...
October 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29057044/6-cyano-analogues-of-bedaquiline-as-less-lipophilic-and-potentially-safer-diarylquinolines-for-tuberculosis
#11
Amy S T Tong, Peter J Choi, Adrian Blaser, Hamish S Sutherland, Sophia K Y Tsang, Jerome Guillemont, Magali Motte, Christopher B Cooper, Koen Andries, Walter Van den Broeck, Scott G Franzblau, Anna M Upton, William A Denny, Brian D Palmer, Daniel Conole
Bedaquiline (1) is a new drug for tuberculosis and the first of the diarylquinoline class. It demonstrates excellent efficacy against TB but induces phospholipidosis at high doses, has a long terminal elimination half-life (due to its high lipophilicity), and exhibits potent hERG channel inhibition, resulting in clinical QTc interval prolongation. A number of structural ring A analogues of bedaquiline have been prepared and evaluated for their anti-M.tb activity (MIC90), with a view to their possible application as less lipophilic second generation compounds...
October 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29038265/verapamil-increases-the-bioavailability-and-efficacy-of-bedaquiline-but-not-clofazimine-in-a-murine-model-of-tuberculosis
#12
Jian Xu, Rokeya Tasneen, Charles A Peloquin, Deepak V Almeida, Si-Yang Li, Kala Barnes-Boyle, Yu Lu, Eric Nuermberger
Drug efflux pumps play an important role in intrinsic and acquired drug resistance. Verapamil, an efflux inhibitor that enhances the activity of bedaquiline, clofazimine and other drugs against Mycobacterium tuberculosis has been proposed as a potential adjunctive agent for treatment of tuberculosis (TB). However, the extent to which verapamil enhances in vivo efficacy by inhibiting bacterial efflux pumps versus inhibiting mammalian drug transporters to improve oral bioavailability has not been delineated. We found that verapamil potentiated the in vitro activity of bedaquiline and clofazimine against M...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29037291/the-devil-we-know-is-the-use-of-injectable-agents-for-the-treatment-of-mdr-tb-justified
#13
A Reuter, P Tisile, D von Delft, H Cox, V Cox, L Ditiu, A Garcia-Prats, S Koenig, E Lessem, R Nathavitharana, J A Seddon, J Stillo, A von Delft, J Furin
For decades, second-line injectable agents (IAs) have been the cornerstone of treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the efficacy of IAs is limited, there is an expanding body of evidence on the serious adverse events caused by these drugs. Here, we present the results of a structured literature review of the safety and efficacy of IAs. We review the continued widespread use of these agents in the context of therapeutic alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from the context of human rights, ethics and patient-centered care...
November 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29025487/incorporating-social-justice-and-stigma-in-cost-effectiveness-analysis-drug-resistant-tuberculosis-treatment
#14
A Zwerling, D Dowdy, A von Delft, H Taylor, M W Merritt
Novel therapies for multidrug-resistant tuberculosis (MDR-TB) are likely to be expensive. The cost of novel drugs (e.g., bedaquiline, delamanid) may be so prohibitively high that a traditional cost-effectiveness analysis (CEA) would rate regimens containing these drugs as not cost-effective. Traditional CEA may not appropriately account for considerations of social justice, and may put the most disadvantaged populations at greater risk. Using the example of novel drug regimens for MDR-TB, we propose a novel methodology, 'justice-enhanced CEA', and demonstrate how such an approach can simultaneously assess social justice impacts alongside traditional cost-effectiveness ratios...
November 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28980217/incremental-cost-effectiveness-of-bedaquiline-for-the-treatment-of-rifampicin-resistant-tuberculosis-in-south-africa-model-based-analysis
#15
Kathryn Schnippel, Cynthia Firnhaber, Francesca Conradie, Norbert Ndjeka, Edina Sinanovic
BACKGROUND: Nearly 20,000 people were diagnosed with multi-drug and rifampicin-resistant tuberculosis (MDR/RR-TB) in South Africa in 2015, yet only one-half of the patients who start treatment are expected to have a successful outcome. There is increasing evidence of the effectiveness and safety of new drug regimens containing bedaquiline for MDR/RR-TB; however, whether they are affordable for high-burden, limited-resource settings is uncertain. OBJECTIVE: Our objective was to determine the incremental cost effectiveness of a bedaquiline-based regimen for MDR/RR-TB treatment in South Africa compared with the standard kanamycin-based regimen...
October 4, 2017: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/28961790/modelling-of-mycobacterial-load-reveals-bedaquiline-s-exposure-response-relationship-in-patients-with-drug-resistant-tb
#16
Elin M Svensson, Mats O Karlsson
Background: Bedaquiline has been shown to reduce time to sputum culture conversion (SCC) and increase cure rates in patients with drug-resistant TB, but the influence of drug exposure remains uncharacterized. Objectives: To investigate whether an exposure-response relationship could be characterized by making better use of the existing information on pharmacokinetics and longitudinal measurements of mycobacterial load. Methods: Quantitative culture data in the form of time to positivity (TTP) in mycobacterial growth indicator tubes obtained from a randomized placebo-controlled Phase IIb registration trial were examined using non-linear mixed-effects methodology...
September 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28941848/drug-development-against-tuberculosis-past-present-and-future
#17
REVIEW
Mahesh S Vasava, Manoj N Bhoi, Sanjay K Rathwa, Mayuri A Borad, Sneha G Nair, Hitesh D Patel
Infection of Mycobacterium tuberculosis (MTB) was observed as early as 5000 years ago with evidence, which is a primeval enemy of the humanoid race. MTB is the pathogen which is responsible for causing the infectious disease tuberculosis; it remains a major cause of morbidity and mortality in poor low-income countries as well as in developing countries because of non-availability of reliable laboratory facilities. The current treatment for drug-resistant tuberculosis (TB) is lengthy, complex, and connected with severe harmful side effects and poor outcomes...
October 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28887015/bedaquiline-or-delamanid-for-rifampin-resistant-tuberculosis
#18
Erica Lessem, Vivian Cox, Jennifer Furin
No abstract text is available yet for this article.
October 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28840010/delamanid-and-bedaquiline-to-treat-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-in-children-a-systematic-review
#19
REVIEW
Lia D'Ambrosio, Rosella Centis, Simon Tiberi, Marina Tadolini, Margareth Dalcolmo, Adrian Rendon, Susanna Esposito, Giovanni Battista Migliori
The new drugs delamanid and bedaquiline are increasingly used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). As evidence is lacking, the World Health Organization recommends their use under specific conditions in adults, delamanid only being recommended in children ≥6 years of age. No systematic review has yet evaluated the efficacy, safety and tolerability of the new drugs in children. A search of peer-reviewed, scientific evidence was performed, to evaluate the efficacy/effectiveness, safety, and tolerability of delamanid or bedaquiline-containing regimens in children with confirmed M/XDR-TB...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28826458/an-lc-ms-ms-based-method-to-analyze-the-anti-tuberculosis-drug-bedaquiline-in-hair
#20
John Metcalfe, Roy Gerona, Anita Wen, Peter Bacchetti, Monica Gandhi
No abstract text is available yet for this article.
September 1, 2017: International Journal of Tuberculosis and Lung Disease
keyword
keyword
10678
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"