tuberculosis
PharmacologyPopulation Pharmacokinetics of the Antituberculosis Agent PretomanidA population pharmacokinetic (PopPK) model for pretomanid was developed using data from 14 studies in the pretomanid development program: six phase 1 studies, six phase 2 studies, and two phase 3 studies. The final analysis data set contained 17,725 observations from 1,054 subjects, including healthy subjects and subjects with drug-sensitive, multidrug-resistant, or extensively drug-resistant pulmonary tuberculosis dosed pretomanid in...
Clinical TherapeuticsEffect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years OldNevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection.
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Clinical TherapeuticsLong-Term Effects on QT Prolongation of Pretomanid Alone and in Combinations in Patients with TuberculosisConcentration-QTc modeling was applied to pretomanid, a new nitroimidazooxazine antituberculosis drug. Data came from eight phase 2 and phase 3 studies.
Editor's Pick PharmacologyModel-Based Relationship between the Molecular Bacterial Load Assay and Time to Positivity in Liquid CultureThe molecular bacterial load (MBL) assay is a new tuberculosis biomarker which provides results in ∼4 hours. The relationship between MBL and time-to-positivity (TTP) has not been thoroughly studied, and predictive models do not exist. We aimed to develop a model for MBL and identify the MBL-TTP relationship in patients.
![1<em>H</em>-Benzo[<em>d</em>]Imidazole Derivatives Affect MmpL3 in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>](https://aac.asm.org/sites/default/files/styles/thumbnail/public/externals/0284aba2d9c90d343ecad3753723bc65.jpg?itok=g4CsECuU)
Mechanisms of Action: Physiological Effects1H-Benzo[d]Imidazole Derivatives Affect MmpL3 in Mycobacterium tuberculosis1H-benzo[d]imidazole derivatives exhibit antitubercular activity in vitro at a nanomolar range of concentrations and are not toxic to human cells, but their mode of action remains unknown. Here, we showed that these compounds are active against intracellular Mycobacterium tuberculosis.
Experimental TherapeuticsDelamanid Central Nervous System Pharmacokinetics in Tuberculous Meningitis in Rabbits and HumansCentral nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculous meningitis (TBM) specifically are nearly uniformly fatal, with little information being available to guide the treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated anti-TB drug with a low MIC (1 to 12 ng/ml) against...
Mechanisms of ResistanceAcquisition of Cross-Resistance to Bedaquiline and Clofazimine following Treatment for Tuberculosis in PakistanWe report on the first six cases of acquired resistance to bedaquiline in Pakistan. Seventy sequential isolates from 30 drug-resistant-tuberculosis patients on bedaquiline-containing regimens were retrospectively tested for bedaquiline resistance by MIC testing and by the detection of mutations in relevant genes. We documented cases failing therapy that developed specific mutations in Rv0678 and had increased MICs associated...
Editor's Pick Clinical TherapeuticsFirst-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis TreatmentThis first-time-in-human (FTIH) study evaluated the safety, tolerability, pharmacokinetics, and food effect of single and repeat oral doses of GSK3036656, a leucyl-tRNA synthetase inhibitor. In part A, GSK3036656 single doses of 5 mg (fed and fasted), 15 mg, and 25 mg and placebo were administered. In part B, repeat doses of 5 and 15 mg and placebo were administered for 14 days once daily.
Experimental TherapeuticsIdentifying Regimens Containing TBI-166, a New Drug Candidate against Mycobacterium tuberculosis In Vitro and In VivoTBI-166, derived from riminophenazine analogues, is under development in a phase I clinical trial in China. TBI-166 showed more potent anti-tuberculosis (anti-TB) activity than did clofazimine in in vitro and animal experiments.
Clinical TherapeuticsLimited Sampling Strategies Using Linear Regression and the Bayesian Approach for Therapeutic Drug Monitoring of Moxifloxacin in Tuberculosis PatientsTherapeutic drug monitoring (TDM) of moxifloxacin is recommended to improve the response to tuberculosis treatment and reduce acquired drug resistance. Limited sampling strategies (LSSs) are able to reduce the burden of TDM by using a small number of appropriately timed samples to estimate the parameter of interest, the area under the concentration-time curve.