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Systematic Review on 1,2,3-Oxadiazoles, 1,2,4-Oxadiazoles, and 1,2,5-Oxadiazoles in the Antimycobacterial Drug Discovery.
ChemMedChem
January 2025
Charles University Faculty of Pharmacy in Hradec Kralove: Univerzita Karlova Farmaceuticka fakulta v Hradci Kralove, Dept. of pharmaceutical chemistry and pharmaceutical analysis, Ak. Heyrovskeho 1203/8, 50003, Hradec Kralove, Czech Republic, CZECHIA.
Tuberculosis remains a leading global health threat, exacerbated by the emergence of multi-drug-resistant strains. The search for novel therapeutic agents is critical in addressing this challenge. This review systematically summarizes the potential of oxadiazole derivatives as promising candidates in antimycobacterial drug discovery.
View Article and Find Full Text PDFSusceptibility Patterns in Clinical Isolates of Complex from a Hospital in Southern Spain.
Microorganisms
December 2024
Servicio de Microbiología, University Hospital Virgen de las Nieves, 18014 Granada, Spain.
The incidence of infections caused by the complex (MAC) has risen significantly, posing diagnostic and therapeutic challenges. This study analyzed 134 clinical isolates of the complex from southern Spain, performing in vitro antimicrobial susceptibility testing using a commercial microdilution technique to generate additional data, refine treatment strategies, and improve patient outcomes. Phenotypic susceptibility testing revealed clarithromycin and amikacin as the most effective antibiotics, with susceptibility rates exceeding 90%, while linezolid and moxifloxacin exhibited limited activity, with resistance rates of 49.
View Article and Find Full Text PDFIntroduction: The TriAD study will assess the Xpert MTB/XDR (Xpert XDR; Cepheid) assay to detect tuberculosis (TB) drug resistance in sputum testing positive for TB to rapidly triage and treat patients with a short all-oral treatment regimen.
Methods And Analysis: In this study, approximately 4800 Xpert MTB/RIF or Ultra MTB-positive patients (irrespective of rifampicin (RIF) resistance (RR) status) from several clinical sites across South Africa, Nigeria and Ethiopia will be enrolled over 18-24 months and followed-up for approximately 6 months post-TB treatment completion. Participants will be enrolled into one of two cohorts based on Xpert MTB/RIF and Xpert XDR results: () positive participants with RR in Cohort 1 (n=880) and positive RIF susceptible TB patients with isoniazid mono-resistance irrespective of presence of resistance to fluoroquinolones, second-line injectable drugs or ethionamide in Cohort 2 (n=400).
Leveraging large-scale Mycobacterium tuberculosis whole genome sequence data to characterise drug-resistant mutations using machine learning and statistical approaches.
Sci Rep
November 2024
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global public health problem, resulting in > 1 million deaths each year. Drug resistance (DR), including the multi-drug form (MDR-TB), is challenging control of the disease. Whilst many DR mutations in the Mtb genome are known, analysis of large datasets generated using whole genome sequencing (WGS) platforms can reveal new variants through the assessment of genotype-phenotype associations.
View Article and Find Full Text PDFSynthesis, Biological Evaluation, Molecular Docking Studies and ADMET Prediction of Oxindole-Based Hybrids for the Treatment of Tuberculosis.
Curr Comput Aided Drug Des
October 2024
Parul Institute of Pharmacy & Research, Parul University Department of Pharmacology Vadodara India.
Article Synopsis
- Tuberculosis (TB) remains a major global health issue, causing an estimated 1.4 million deaths in 2019, highlighting the need for new treatment options due to existing drug resistance and side effects.
- This study focuses on the development of oxindole-based hybrids as potential InhA inhibitors to combat Mycobacterium tuberculosis, involving both anti-mycobacterial activity evaluations and molecular docking studies to understand drug interactions.
- Among the synthesized compounds, 8b demonstrated strong anti-mycobacterial activity and a favorable safety profile, showing promise as a new treatment and adhering to established drug-likeness criteria.
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