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drug-resistant tuberculosis

  • Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis
    Clinical Therapeutics
    Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis

    The prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an fAUC (...

    Wael A. Alghamdi, Mohammad H. Al-Shaer, Guohua An, Abdullah Alsultan, Maia Kipiani, Ketevan Barbakadze, Lali Mikiashvili, David Ashkin, David E. Griffith, J. Peter Cegielski, Russell R. Kempker, Charles A. Peloquin
  • Utility of Targeted, Amplicon-Based Deep Sequencing To Detect Resistance to First-Line Tuberculosis Drugs in Botswana
    Analytical Procedures
    Utility of Targeted, Amplicon-Based Deep Sequencing To Detect Resistance to First-Line Tuberculosis Drugs in Botswana

    Multidrug-resistant tuberculosis (TB) is an alarming threat, and targeted deep sequencing (DS) may be an effective method for rapid identification of drug-resistant profiles, including detection of heteroresistance. We evaluated the sensitivity and specificity of targeted DS versus phenotypic drug susceptibility testing (pDST) among patients starting first-line anti-TB therapy in Botswana. Overall, we found high concordance between DS...

    Qiao Wang, Chawangwa Modongo, Christopher Allender, David M. Engelthaler, Robin M. Warren, Nicola M. Zetola, Sanghyuk S. Shin
  • Open Access
    Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis
    Clinical Therapeutics
    Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis

    Limited pharmacokinetic/pharmacodynamic (PK/PD) data exist on cycloserine in tuberculosis (TB) patients. We pooled several studies into a large PK data set to estimate the population PK parameters for cycloserine in TB patients.

    Wael A. Alghamdi, Abdullah Alsultan, Mohammad H. Al-Shaer, Guohua An, Shahriar Ahmed, Yosra Alkabab, Sayera Banu, Ketevan Barbakadze, Eric Houpt, Maia Kipiani, Lali Mikiashvili, Stephan Schmidt, Scott K. Heysell, Russell R. Kempker, J. Peter Cegielski, Charles A. Peloquin
  • Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection
    Clinical Therapeutics
    Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection

    The World Health Organization (WHO) recently recommended that linezolid be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in patients with this disease. We conducted an observational study to explore covariate effects on linezolid PK and to estimate the probability of PK/pharmacodynamic target attainment in South African patients with drug-resistant TB....

    Sean Wasserman, Paolo Denti, James C. M. Brust, Mahmoud Abdelwahab, Siphokazi Hlungulu, Lubbe Wiesner, Jennifer Norman, Frederick A. Sirgel, Robin M. Warren, Aliasgar Esmail, Keertan Dheda, Neel R. Gandhi, Graeme Meintjes, Gary Maartens
  • Mechanisms of Resistance
    Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance
    John Z. Metcalfe, Elizabeth Streicher, Grant Theron, Rebecca E. Colman, Renee Penaloza, Christopher Allender, Darrin Lemmer, Robin M. Warren, David M. Engelthaler
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