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Fluoroquinolones and rifampin combination in the backdrop of heteroresistant tuberculosis.
Antimicrob Agents Chemother
January 2025
Division of Infectious Diseases, Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, Texas, USA.
The impact of heteroresistance on tuberculosis (TB) treatment outcomes is unclear, as is the role of different rifampin and isoniazid exposures on developing resistance mutations. Hollow fiber system model of TB (HFS-TB) units were inoculated with drug-susceptible () and treated with isoniazid and rifampin exposure identified in a clinical trial as leading to treatment failure and acquired drug resistance. Systems were sampled for drug concentration measurements, estimation of total and drug-resistant , and small molecule overlapping reads (SMOR) analysis for the detection of heteroresistance.
View Article and Find Full Text PDFChildren and providers' perspectives on once-weekly rifapentine and isoniazid TB preventive therapy.
IJTLD Open
January 2025
Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Background: TB preventive treatment (TPT) prevents the development of TB disease in individuals at risk of progression from infection to disease. However, implementation of TPT for children is poor in most high-burden settings. The long duration and pill burden of the 6-month once-daily isoniazid regimen (6H) pose significant barriers to completion.
View Article and Find Full Text PDFSafety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.
Lancet Microbe
December 2024
Institute of Infectious Diseases and Tropical Medicine, LMU University Hospital, LMU Munich, Germany; German Center for Infection Research, Munich Partner Site, Munich, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology, Infection, and Pandemic Research, Munich, Germany; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address:
Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.
Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.
New Ionic Liquid Forms of Antituberculosis Drug Combinations for Optimized Stability and Dissolution.
AAPS PharmSciTech
January 2025
Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Isoniazid (INH) and rifampicin (RIF) are the two main drugs used for the management of tuberculosis. They are often used as a fixed drug combination, but their delivery is challenged by suboptimal solubility and physical instability. This study explores the potential of active pharmaceutical ingredient-ionic liquids (API-ILs) to improve the physicochemical and pharmaceutical properties of INH and RIF.
View Article and Find Full Text PDFThe Development of an Age-Appropriate Fixed Dose Combination for Tuberculosis Using Physiologically-Based Pharmacokinetic Modeling (PBBM) and Risk Assessment.
Pharmaceutics
December 2024
Simulations Plus, Inc., 42505 10th Street West, Lancaster, CA 93534-7059, USA.
The combination of isoniazid (INH) and rifampicin (RIF) is indicated for the treatment maintenance phase of tuberculosis (TB) in adults and children. In Brazil, there is no current reference listed drug for this indication in children. Farmanguinhos has undertaken the development of an age-appropriate dispersible tablet to be taken with water for all age groups from birth to adolescence.
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