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Emergence of antibiotic-specific phenotypes during prolonged treatment of mice.
Antimicrob Agents Chemother
January 2025
Rocky Mountain Regional VA Medical Center, Aurora, Colorado, USA.
A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiology of (), which may enable the pathogen to withstand treatment. While antibiotic-treated has been evaluated in experiments it is unclear if and how long-term treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affects physiologic processes differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the transcriptome in the BALB/c high-dose aerosol infection mouse model following 4 weeks of treatment with three sterilizing and three non-sterilizing antibiotics.
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.
Executive Summary: Clinical Practice Guidelines on the Management of Resistant Tuberculosis of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).
Arch Bronconeumol
December 2024
Pulmonology Service, Cruces University Hospital (OSI EEC), Barakaldo, Spain; BioBizkaia Health Research Institute, Spain.
The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) have developed together Clinical Practice Guidelines (GPC) on the management of people affected by tuberculosis (TB) resistant to drugs with activity against Mycobacterium tuberculosis. These clinical practice guidelines include the latest updates of the SEPAR regulations for the diagnosis and treatment of drug-resistant TB from 2017 and 2020 as the starting point. The methodology included asking relevant clinical questions based on PICO methodology, a literature search focusing on each question, and a systematic and comprehensive evaluation of the evidence, with a summary of this evidence for each question.
View Article and Find Full Text PDFOptimizing Pyrazinamide Use: A Low-Hanging Fruit in Improving Outcomes with Tuberculous Meningitis? Narrative Review.
Infect Dis Ther
January 2025
Christian Medical College, Vellore, Tamil Nadu, India.
Tuberculous meningitis (TBM) disables more than a third of its sufferers. Recent research has focused on optimizing the antitubercular regimen, mainly by increasing the dosage of rifampicin. However, pyrazinamide, with higher penetration into the central nervous system, is generally overlooked.
View Article and Find Full Text PDFThe epidemiology and gene mutation characteristics of pyrazinamide-resistant clinical isolates in Southern China.
Emerg Microbes Infect
December 2025
State Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis Research, Department of Tuberculosis, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangdong, People's Republic of China.
This study investigates the epidemic trend of pyrazinamide (PZA)-resistant tuberculosis in Southern China over 11 years (2012-2022) and evaluates the mutation characteristics of PZA resistance-related genes ( and ) in clinical () isolates. To fulfil these goals, we analyzed the phenotypic PZA resistance characteristics of 14,927 clinical isolates for which Bactec MGIT 960 PZA drug susceptibility testing (DST) results were available, revealing that 2,054 (13.76%) isolates were resistant to PZA.
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