A5017847957- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Resistance in Bacteria
- Quinazolinone synthesis and applications
- Cancer therapeutics and mechanisms
- Infectious Diseases and Tuberculosis
- Infectious Diseases and Mycology
- Pneumonia and Respiratory Infections
- Pneumocystis jirovecii pneumonia detection and treatment
- Helicobacter pylori-related gastroenterology studies
- Antimicrobial Resistance in Staphylococcus
- Diagnosis and treatment of tuberculosis
- Drug-Induced Hepatotoxicity and Protection
- Drug Transport and Resistance Mechanisms
- Liver Disease and Transplantation
- HIV/AIDS drug development and treatment
- Pharmacogenetics and Drug Metabolism
- Veterinary medicine and infectious diseases
- Phenothiazines and Benzothiazines Synthesis and Activities
- Actinomycetales infections and treatment
- Biosimilars and Bioanalytical Methods
- Microwave-Assisted Synthesis and Applications
- RNA modifications and cancer
- MicroRNA in disease regulation
The University of Texas at Tyler
2021-2025
The University of Texas Health Science Center at Tyler
2020-2025
St.John's Medical College Hospital
2024
Baylor University Medical Center
2015-2023
Texas Tech University
2019-2023
The University of Texas Southwestern Medical Center
2010-2022
Southwestern Medical Center
2008-2022
Texas Tech University Health Sciences Center
2019-2022
North Eastern Hill University
2020
Conference Board
2020
(See the editorial commentary by Dartois, on pages 1827–9.) Background. It is believed that nonadherence proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level associated with emergence MDR-tuberculosis unknown. Performance a randomized controlled trial in which some patients are to would be unethical; therefore, other study designs should utilized. Methods. We performed hollow fiber studies for both bactericidal and sterilizing effect, inoculum spiked...
We hypothesize that low-level efflux pump expression is the first step in development of high-level drug resistance mycobacteria. performed 28-day azithromycin dose-effect and dose-scheduling studies our hollow-fiber model disseminated Mycobacterium avium-M. intracellulare complex. Both microbial kill emergence were most closely linked to within-macrophage area under concentration-time curve (AUC)/MIC ratio. Quantitative PCR revealed subtherapeutic exposures over 3 days led a 56-fold...
Acquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the and how it arises remain poorly understood.To identify relationship between drug concentrations susceptibility readouts (minimum inhibitory [MICs]) in TB cavity.We recruited patients medically incurable who were undergoing therapeutic lung resection while on a cocktail second-line anti-TB drugs. On day surgery, antibiotic measured blood...
Background. Ethambutol is used for the treatment of tuberculosis in cases where there isoniazid resistance. We examined emergence drug resistance to ethambutol monotherapy pharmacokinetic-pharmacodynamic studies a hollow-fiber system.
Background. The role of drug concentrations in clinical outcomes children with tuberculosis is unclear. Target for dose optimization are unknown. Methods. Plasma measured Indian were modeled using compartmental pharmacokinetic analyses. followed until end therapy to ascertain failure or death. An ensemble artificial intelligence algorithms, including random forests, was used identify predictors outcome from among 30 clinical, laboratory, and variables. Results. Among the 143 known outcomes,...
ABSTRACT Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed linezolid dose-effect dose-scheduling studies the hollow fiber system model of (HFS-TB) for effect. HFS-TB units were treated with several doses to mimic human-like intrapulmonary pharmacokinetics repetitively sampled drug concentration, total bacterial burden, linezolid-resistant subpopulations, RNA...
Levofloxacin is used for the treatment of multidrug-resistant tuberculosis; however optimal dose unknown.We hollow fiber system model tuberculosis (HFS-TB) to identify 0-24 hour area under concentration-time curve (AUC0-24) minimum inhibitory concentration (MIC) ratios associated with maximal microbial kill and suppression acquired drug resistance (ADR) Mycobacterium (Mtb). Levofloxacin-resistant isolates underwent whole-genome sequencing. Ten thousands patient Monte Carlo experiments (MCEs)...
BACKGROUND: Optimal drug dosing is important to ensure adequate response treatment, prevent development of resistance and reduce toxicity. The aim these clinical standards provide guidance on 'best practice´ for management TB drugs.METHODS: A panel 57 global experts in the fields microbiology, pharmacology care were identified; 51 participated a Delphi process. 5-point Likert scale was used score draft standards. final document represents broad consensus approved by all participants.RESULTS:...
Ceftazidime-avibactam is highly efficacious against extensive- and multidrug-resistant strains of Mycobacterium tuberculosis .
ABSTRACT Mycobacterium abscessus causes chronic pulmonary infections that are extremely difficult to cure. The currently recommended combination therapy is associated with high failure rates and relapse. Tigecycline has been explored in salvage regimens, a response rate of 43% those who received at least month therapy. We performed dose-response study hollow-fiber system model M. infection which we recapitulated tigecycline human concentration-time profiles 8 different doses for 21 days....
In a hollow-fiber model, we mimicked the drug exposures achieved in lungs of humans treated with standard amikacin, clarithromycin, and cefoxitin combination therapy for Mycobacterium abscessus infection. At optimal dosing, kill rate -0.09 (95% confidence interval, -0.04 to 0.03) log10 CFU per ml/day was over first 14 days, after which there regrowth due acquired resistance. Thus, regimen quickly failed. A new is needed.
Rationale: A human model to better understand tuberculosis immunopathogenesis and facilitate vaccine development is urgently needed.Objectives: We evaluated the feasibility, safety, immunogenicity of live bacillus Calmette-Guérin (BCG) in a lung-oriented controlled infection model.Methods: recruited 106 healthy South African participants with varying degrees susceptibility. Live BCG, sterile PPD, saline were bronchoscopically instilled into separate lung segments (n = 65). control group 34)...
Adverse effects (AE) to TB treatment cause morbidity, mortality and interruption. The aim of these clinical standards is encourage best practise for the diagnosis management AE.
Ethambutol, together with a macrolide, is the backbone for treatment of disseminated Mycobacterium avium disease. However, at standard dose 15 mg/kg body weight/day, ethambutol efficacy limited. In addition, susceptibility breakpoints have consistently failed to predict clinical outcome. We performed dose-effect studies extracellular M. as well bacilli within human macrophages. The maximal kill rate (E(max)) against was 5.54 log(10) CFU/ml, compared 0.67 CFU/ml intracellular avium, after 7...
The treatment of pulmonary Mycobacterium abscessus disease is associated with very high failure rates and easily acquired drug resistance. Amikacin the key in regimens, but optimal doses are unknown. No good preclinical model exists to perform formal pharmacokinetics/pharmacodynamics experiments determine these doses. We developed a hollow-fiber system M. studied amikacin exposure effects dose scheduling. mimicked human pharmacokinetics. Both microbial kill resistance were linked peak...
Treatment of disseminated tuberculosis in children ≤ 6 years has not been optimized. The pyrazinamide-containing combination regimen used to treat babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due hepatotoxicity worries, there are no dose–response studies children. We designed a hollow fiber system model intracellular with co-perfused three-dimensional organotypic liver modules simultaneously test for efficacy toxicity. utilized pediatric pharmacokinetics...
Background. The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model pediatric intracellular tuberculosis. However, its kill rate slower than standard 3-drug isoniazid, rifampin, pyrazinamide. We wanted examine effect adding a third oral agent, faropenem, this dual combination. Methods. performed series studies Mycobacterium tuberculosis, by mimicking pharmacokinetics each antibiotic. First, we varied percentage time that faropenem persisted...
The current treatment regimens recommended for Mycobacterium abscessus subspecies (Mab) pulmonary disease are not effective. We identified 16 drugs with potential to build new regimens, translating 560 possible three-drug combination regimens.