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Treatment outcomes of extensively drug-resistant tuberculosis (xdr-tb) in mongolia: retrospective study
Conclusion: The treatment success rate of XDR-TB cases was 48.6%. It is three-fold higher with the BPaL regimen than with previous regimens, and the progression rate was significantly improved.Keywords: Extensively drug-resistant TB, BPaL, Bedaquiline (Source: European Respiratory Journal)
Source: European Respiratory Journal - October 27, 2023 Category: Respiratory Medicine Authors: Baigabyl, B., Rash, B., Adilaa, O., Purevsuren, Y., Radnaa, D. Tags: Tuberculosis and non-tuberculous mycobacterial diseases Source Type: research

Seventeen drugs, one sample: analyzing multiple anti-TB drugs simultaneously using one method
In conclusion, we developed a method to analyze 17 anti-TB drugs simultaneously in one sample of plasma, serum or saliva: all first-line, BPaLM, and 9m all oral regimen for MDR/RR-TB drugs, and 63% of the longer MDR-TB regimen drugs. This method will save time and will further optimize therapeutic drug monitoring. (Source: European Respiratory Journal)
Source: European Respiratory Journal - October 27, 2023 Category: Respiratory Medicine Authors: Bolhuis, M. S., Jongedijk, E. M., Akkerman, O. W., Touw, D. J., Sturkenboom, M. G. G. Tags: Tuberculosis and non-tuberculous mycobacterial diseases Source Type: research

Synthesis, characterization, in vitro antimycobacterial and cytotoxicity evaluation, DFT calculations, molecular docking and ADME studies of new isomeric benzimidazole-1,2,3-triazole-quinoline hybrid mixtures
Bioorg Chem. 2023 Oct 9;141:106904. doi: 10.1016/j.bioorg.2023.106904. Online ahead of print.ABSTRACTNew benzimidazole-1,2,3-triazole-quinoline hybrids and their intermediates, differing in substitutions at the C-2 and/or C6 positions of the benzimidazole ring, were successfully synthesized in 55---80 % yields, with the C6-substituted ones forming as inseparable tautomeric mixtures. The synthesized compounds were fully characterised by FT-IR, 1D- and 2D-NMR, and HRMS. In-depth NMR analysis and DFT molecular calculations showed that the tautomeric mixtures formed in a ratio of almost 1:1 ratio (cis and trans), except for 5 ...
Source: Bioorganic Chemistry - October 13, 2023 Category: Chemistry Authors: Nombulelo T P Nyoni Nomagugu B Ncube Mbali X Kubheka Nompumelelo P Mkhwanazi Sibusiso Senzani Thishana Singh Matshawandile Tukulula Source Type: research

Coadministration of bedaquiline and pyrifazimine reduce exposure to toxic metabolite N-desmethyl bedaquiline
Conclusions: In conclusion, our results showed that the combination of BDQ and TBI-166 significantly reduced exposure to the toxic metabolite M2 by inhibiting the activity of the CYP3A4 pathway. The potential safety and efficacy benefits demonstrated by the TB treatment highly suggest that coadministration of BDQ and TBI-166 should be studied further. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - October 4, 2023 Category: Drugs & Pharmacology Source Type: research

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC)
Pharmaceuticals (Basel). 2023 Sep 15;16(9):1309. doi: 10.3390/ph16091309.ABSTRACTNon-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range ...
Source: Cancer Control - September 28, 2023 Category: Cancer & Oncology Authors: Shehla Nasar Mir Najib Ullah Obaid Afzal Abdulmalik Saleh Alfawaz Altamimi Manal A Alossaimi Waleed H Almalki Abdulaziz Alzahrani Md Abul Barkat Tahani M Almeleebia Hanan Alshareef Eman M Shorog Gyas Khan Tanuja Singh J K Singh Source Type: research

Intricate link between siderophore secretion and drug efflux in Mycobacterium tuberculosis 
In this study, we show that M. tuberculosis mutants lacking components of the MmpS4-MmpL4 and MmpS5-MmpL5 systems are more susceptible to bedaquiline, clofazimine, and rifabutin, important drugs for treatment of drug-resistant TB. While genetic deletion experiments revealed similar functions of the MmpL4 and MmpL5 transporters in siderophore and drug secretion, complementation experiments indicated that the MmpS4-MmpL4 proteins alone are not sufficient to restore drug efflux in an M. tuberculosis mutant lacking both operons, in contrast to MmpS5-MmpL5. Importantly, an M. tuberculosis mutant lacking the recently discovered ...
Source: Antimicrobial Agents and Chemotherapy - September 7, 2023 Category: Microbiology Authors: Virginia Meikle Lei Zhang Michael Niederweis Source Type: research

Bedaquiline-based all-oral regimen for macrolide-resistant Mycobacterium abscessus pulmonary disease
(Source: International Journal of Tuberculosis and Lung Disease)
Source: International Journal of Tuberculosis and Lung Disease - August 24, 2023 Category: Respiratory Medicine Authors: Riccardi, N. Occhineri, S. Matucci, T. Marchetti, G. Rindi, L. Tiseo, G. Cirillo, D. M. Falcone, M. Tags: FORUM-Correspondence Source Type: research

Antibacterial activity of the novel compound Sudapyridine (WX-081) against Mycobacterium abscessus
ConclusionWX-081 effectively inhibited M. abscessus growth in vitro and in vivo and prolonged survival of M. abscessus-infected zebrafish, thus indicating that WX-081 holds promise as a clinical treatment for M. abscessus infection. (Source: Frontiers in cellular and infection microbiology)
Source: Frontiers in cellular and infection microbiology - August 17, 2023 Category: Microbiology Source Type: research

Lung microenvironments harbor Mycobacterium tuberculosis phenotypes with distinct treatment responses
Antimicrob Agents Chemother. 2023 Aug 11:e0028423. doi: 10.1128/aac.00284-23. Online ahead of print.ABSTRACTTuberculosis lung lesions are complex and harbor heterogeneous microenvironments that influence antibiotic effectiveness. Major strides have been made recently in understanding drug pharmacokinetics in pulmonary lesions, but the bacterial phenotypes that arise under these conditions and their contribution to drug tolerance are poorly understood. A pharmacodynamic marker called the RS ratio® quantifies ongoing rRNA synthesis based on the abundance of newly synthesized precursor rRNA relative to mature structural rRNA...
Source: Antimicrobial Agents and Chemotherapy - August 11, 2023 Category: Microbiology Authors: Nicholas D Walter Jackie P Ernest Christian Dide-Agossou Allison A Bauman Michelle E Ramey Karen Rossmassler Lisa M Massoudi Samantha Pauly Reem Al Mubarak Martin I Voskuil Firat Kaya Jansy P Sarathy Matthew D Zimmerman V éronique Dartois Brendan K Podel Source Type: research

Characterization of Mycobacterium abscessus colony-biofilms based on bi-dimensional images
Antimicrob Agents Chemother. 2023 Aug 11:e0040223. doi: 10.1128/aac.00402-23. Online ahead of print.ABSTRACTMycobacterium abscessus biofilm aggregates have been shown in the lungs of cystic fibrosis patients and are often tolerant to drugs. Herein, we analyzed bi-dimensional images of either fluorescent or Congo red-stained M. abscessus colony-biofilms grown on a membrane to monitor growth and shape of M. abscessus smooth and rough variants. These colony-biofilms responded differently to rifabutin and bedaquiline, thus highlighting the importance of the morphotype to properly address antibiotic treatment in patients with b...
Source: Antimicrobial Agents and Chemotherapy - August 11, 2023 Category: Microbiology Authors: John Jairo Aguilera-Correa Yves-Marie Boudehen Laurent Kremer Source Type: research