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isoniazid

  • Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Mechanisms of Resistance
    Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis

    Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms and undermine our ability to contain outbreaks.

    Siavash J. Valafar
  • Risk of Serotonin Syndrome with Isoniazid
    Letter to the Editor
    Risk of Serotonin Syndrome with Isoniazid
    Michael E. O’Brien, Ronak G. Gandhi, Camille N. Kotton, Meagan L. Adamsick
  • Acetylation of Isoniazid Is a Novel Mechanism of Isoniazid Resistance in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Mechanisms of Resistance
    Acetylation of Isoniazid Is a Novel Mechanism of Isoniazid Resistance in Mycobacterium tuberculosis

    Isoniazid (INH), one of the first-line drugs used for the treatment of tuberculosis, is a prodrug which is activated by the intracellular KatG enzyme of Mycobacterium tuberculosis. The activated drug hinders cell wall biosynthesis by inhibiting the InhA protein. INH-resistant strains of M. tuberculosis...

    K. B. Arun, Aravind Madhavan, Billu Abraham, M. Balaji, K. C. Sivakumar, P. Nisha, R. Ajay Kumar
  • Characterization of Large Deletion Mutants of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Selected for Isoniazid Resistance
    Mechanisms of Resistance
    Characterization of Large Deletion Mutants of Mycobacterium tuberculosis Selected for Isoniazid Resistance

    Large genomic deletions (LGDs) (6 to 63 kbp) were observed in isoniazid-resistant Mycobacterium tuberculosis mutants derived from four M. tuberculosis strains. These LGDs had no growth defect in vitro but could be defective in intracellular growth and showed various sensitivities toward...

    Catherine Vilchèze, Rajagopalan Saranathan, Brian Weinrick, William R. Jacobs
  • Advanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs <em>In Vitro</em>
    Clinical Therapeutics
    Advanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In Vitro

    One of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our preclinical drug development pipeline. In most available dormancy models, it takes a long time to create a dormant state, and it is difficult to identify and quantify this...

    E. D. Pieterman, M. J. Sarink, C. Sala, S. T. Cole, J. E. M. de Steenwinkel, H. I. Bax
  • KatG as Counterselection Marker for Nontuberculous Mycobacteria
    Letter to the Editor
    KatG as Counterselection Marker for Nontuberculous Mycobacteria
    Aron Gagliardi, Petra Selchow, Sakshi Luthra, Daniel Schäfle, Bettina Schulthess, Peter Sander
  • Open Access
    <em>N</em>-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and <em>N</em>-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment
    Pharmacology
    N-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and N-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment

    The distribution of N-acetyltransferase 2 gene (NAT2) polymorphisms varies considerably among different ethnic groups. Information on NAT2 single-nucleotide polymorphisms in the South African population is limited. We investigated NAT2 polymorphisms and their effect on isoniazid pharmacokinetics (PK) in Zulu black HIV-infected South Africans in Durban, South Africa. HIV-infected participants with...

    Thuli Mthiyane, James Millard, John Adamson, Yusentha Balakrishna, Cathy Connolly, Andrew Owen, Roxana Rustomjee, Keertan Dheda, Helen McIlleron, Alexander S. Pym
  • Population Pharmacokinetic Analysis of Isoniazid among Pulmonary Tuberculosis Patients from China
    Pharmacology
    Population Pharmacokinetic Analysis of Isoniazid among Pulmonary Tuberculosis Patients from China

    The blood concentration of isoniazid (INH) is evidently affected by polymorphisms in N-acetyltransferase 2 (NAT2), an enzyme that is primarily responsible for the trimodal (i.e., fast, intermediate, and slow) INH elimination. The pharmacokinetic (PK) variability, driven largely by NAT2 activity, creates a challenge for the deployment of a uniform INH dosage in tuberculosis (TB) patients.

    Wei Jing, Zhaojing Zong, Bohao Tang, Jing Wang, Tingting Zhang, Shu’an Wen, Yi Xue, Naihui Chu, Wei Zhao, Hairong Huang
  • Differential Sensitivity of Mycobacteria to Isoniazid Is Related to Differences in KatG-Mediated Enzymatic Activation of the Drug
    Mechanisms of Resistance
    Differential Sensitivity of Mycobacteria to Isoniazid Is Related to Differences in KatG-Mediated Enzymatic Activation of the Drug

    Isoniazid (INH) is a cornerstone of antitubercular therapy. Mycobacterium tuberculosis complex bacteria are the only mycobacteria sensitive to clinically relevant concentrations of INH. All other mycobacteria, including M. marinum and M...

    Tali H. Reingewertz, Tom Meyer, Fiona McIntosh, Jaryd Sullivan, Michal Meir, Yung-Fu Chang, Marcel A. Behr, Daniel Barkan
  • Open Access
    Regrowth of <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span> Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth Rate
    Susceptibility
    Regrowth of Mycobacterium tuberculosis Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth Rate

    Modulation of the growth rate in Mycobacterium tuberculosis is key to its survival in the host, particularly with regard to its adaptation during chronic infection, when the growth rate is very slow. The resulting physiological changes influence the way in which this pathogen interacts with the host and responds to antibiotics. Therefore, it is important that we...

    Charlotte L. Hendon-Dunn, Henry Pertinez, Alice A. N. Marriott, Kim A. Hatch, Jon C. Allnutt, Geraint Davies, Joanna Bacon

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