Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 19 of 19 for “"Bedaquiline"”.
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Drug-drug interactions between antiretrovirals and bedaquiline
… are ineffective against drug-resistant TB. Bedaquiline is a new antimycobacterial drug which has shown great promise through its excellent efficacy for treating drug-resistant TB. Being a new drug, however, potential drug interactions with antiretrovirals are a major concern. Bedaquiline is …
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Characterisation of bedaquiline resistance mediated by the <i>M. tuberculosis</i> MmpS5L5 efflux pump
… a toxic combination of less effective drugs. Bedaquiline, an antibiotic that targets the mycobacterial ATP synthase, has revitalised the ability to treat multidrug-resistant tuberculosis as part of new all-oral 6-month antibiotic regimens. Unfortunately, but predictably, clinical resistance to …
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Improved treatment outcomes with bedaquiline when substituted for second-line injectable agents in multidrug-resistant tuberculosis: A retrospective cohort study
Background Bedaquiline is used as a substitute for second-line injectable (SLI) intolerance in the treatment of multidrug-resistant tuberculosis (MDR-TB), but the efficacy and safety of this strategy is unknown. Methods We performed a retrospective cohort study to evaluate treatment outcomes for …
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Efficacy and safety of novel and repurposed drugs for the treatment of drug-resistant tuberculosis
… without any breakthrough discovery, several new (bedaquiline and delamanid) and repurposed drugs (linezolid) are increasingly becoming available for use. However, data regarding the efficacy and safety of these drugs in drug-resistant TB patients, with or without HIV infection, from a real-life …
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Identifying cross-species regimens for the treatment of rapid-growing and slow-growing nontuberculous Mycobacterium pulmonary infections
… and the MIC-adjusted clearance index (MACI). Bedaquiline (BDQ) demonstrated the most consistent single-drug activity across intracellular and in vivo models of M. avium and M. abscessus infection. Macrolides, fluoroquinolones, and rifabutin demonstrated comparable in vitro potency, but had …
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Does the inclusion of the cost and burden of adverse drug reactions associated with drug-resistant TB treatment affect the incremental cost-effectiveness of new treatment regimens? A case study from the introduction of bedaquiline in South Africa National TB Programme
… regulatory authorities approved a new drug, bedaquiline, but only for treatment in cases with no other options. In 2015, the South African Medicines Control Council approved bedaquiline for drug-resistant TB, but only a limited number of doses were approved in the 2016/2017 annual budget and …
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Photoredox activation of SF₆ for fluorination, on-demand automated titration of organometallic reagents in continuous flow, and progress toward an enantioselective synthesis of bedaquiline
… Progress Toward an Enantioselective Synthesis of Bedaquiline [chemical formula] Herein we describe progress toward an enantioselective synthesis of bedaquiline, a novel pharmaceutical used for the treatment of multi-drug resistant tuberculosis. In our efforts, several provisional routes have been …
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Novel methods and syntheses toward HIV/AIDS and tuberculosis pharmaceuticals
… We have proposed a novel synthesis toward bedaquiline, the latest pharmaceutical to be released in the market for the treatment of multi-drug resistant tuberculosis. The synthesis of the final epoxide intermediate of our route has been achieved on multi-gram scale, and the subject of future …
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Robust Processes for Polymer Modification and Pharmaceutical Synthesis
… Yield Major Improvements to the Synthesis of Bedaquiline Bedaquiline fumarate (Sirturo®)is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation-addition …
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Stereoselective and Economical Methods for Chemical Synthesis of Essential Medicines
… small molecule drugs emtricitabine, lamivudine, bedaquiline, and diazepam was investigated. Stereoselective strategies and cost-of-goods reduction more broadly are described. Lastly, a perspective on reproductive health safety in the chemical laboratory is presented. Chapter 1: Diazotization of …
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Pharmacometric modelling to inform and improve TB and HIV treatment: Focus on drug-drug interactions and neglected populations
… interaction of efavirenz, isoniazid, and bedaquiline in pregnant women and characterise the pharmacokinetics and pharmacodynamics of high dose isoniazid in adults with multidrugresistant tuberculosis. We found that isoniazid and efavirenz exposures were reduced during pregnancy, but the …
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Genetic mechanisms contributing to antimicrobial resistance: gene repression in Mycobacterium, gene transfer in Salmonella, and phage sensitivity in Escherichia
… locus mmpT5 increased resistance to anti-TB drug bedaquiline in M. intracellulare lung infections. Based on previous work, MmpT5 is a TetR transcription factor hypothesized to repress expression of the downstream Resistance Nodulation Division (RND) efflux pump mmpSL. To test this, we assembled …
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Three-Dimensional (3D) pharmacophore-based identification of possible ATP-synthase inhibitors for mycobacterium tuberculosis (Mtb)
… drugs (Capreomycin, Kanamycin and Amikacin). Bedaquiline (BDQ) is a diarylquinoline aimed at inhibiting the adenosine triphosphate (ATP) synthase of MDR-TB, thereby targeting the energy metabolism mechanism of Mtb. Drug regimens utilized prior to BDQ have shown low success rates in patients …
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Novel Inhibitors for Isocitrate Lyase as a Potent Antitubercular Agent for Mycobacterium Tuberculosis
… effect of CL-54-04 with rifampicin or bedaquiline in both glycerol and propionate media. To investigate the role of acetate metabolism in drug tolerance, ΔpckA, ICL knock-down and ΔprpD Mtb mutants were assessed. Results: Seven new conditions to crystallise ICL1 were identified, and …
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SYNTHESIS, CHARACTERIZATION AND EVALUATION OF BIOACTIVE MOLECULES LINKED TO PHOTOREMOVABLE PROTECTING GROUPS FOR SPATIO-TEMPORAL CONTROL OF THEIR ACTIVITY THROUGH PHOTOACTIVATION
… on the photocaging of the antitubercular drug bedaquiline, a highly potent agent against Mycobacterium tuberculosis due to its ability to deplete ATP resources by inhibiting the enzyme ATP synthase (ATPe). However, its clinical use is limited by severe cardiac and hepatic toxicities. The …
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Population pharmacokinetic and pharmacodynamic modelling to improve tuberculosis treatment
… on both new anti-tuberculosis agents such as bedaquiline, delamanid, and pretomanid and repurposed drugs, such as linezolid and clofazimine. In this thesis, we employed nonlinear mixed-effects modelling to evaluate the pharmacokinetics of first-line tuberculosis drugs isoniazid, pyrazinamide, …
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Repurposing chlorpromazine and its metabolites for antituberculosis drug discovery
… assays, the use of RIF with M3 and M5, bedaquiline (BDQ) with M2, and SPEC with M3 were bactericidal. At 140μM, CPZ and M1, M2, M3 treated samples exhibited a 2-fold up-regulation of the cydA (Rv1623c) gene which encodes an essential subunit of the cytochrome bd-type menaquinol oxidase …
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Evaluation of the costs of managing cutaneous adverse drug reactions to first-line TB therapy in South African TB patients
… second-line regimens containing rifabutin, bedaquiline and delamanid cost 44-55% less than drug rechallenge depending on the drug regimen used ($2,651/patient to $3,276/patient). Sensitivity analyses indicated that drug rechallenge was most sensitive to hospitalisation costs, whereas …
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Investigating permeation of anti-mycobacterial agents in Mycobacterium tuberculosis and M. tuberculosis-infected macrophages in vitro as a model for early stage tuberculosis drug discovery
… Moxifloxacin (MXF), levofloxacin (LVF), bedaquiline (BDQ), rifampicin (RIF) and clofazimine (CFZ) were included for reference as known anti-TB drugs with varying lipophilicities. In chapter 2, FA and derivatives showed potent antimycobacterial activity (~1 µM) with selectivity indices …