isoniazid
Mechanisms of ResistanceCharacterization of Large Deletion Mutants of Mycobacterium tuberculosis Selected for Isoniazid ResistanceLarge 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...
Clinical TherapeuticsAdvanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In VitroOne 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...
Letter to the EditorKatG as Counterselection Marker for Nontuberculous Mycobacteria
PharmacologyN-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and N-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis TreatmentThe 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...
PharmacologyPopulation Pharmacokinetic Analysis of Isoniazid among Pulmonary Tuberculosis Patients from ChinaThe 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.
Mechanisms of ResistanceDifferential Sensitivity of Mycobacteria to Isoniazid Is Related to Differences in KatG-Mediated Enzymatic Activation of the DrugIsoniazid (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...
SusceptibilityRegrowth of Mycobacterium tuberculosis Populations Exposed to Antibiotic Combinations Is Due to the Presence of Isoniazid and Not Bacterial Growth RateModulation 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...
PharmacologyHepatotoxicity Induced by Isoniazid-Lipopolysaccharide through Endoplasmic Reticulum Stress, Autophagy, and Apoptosis Pathways in ZebrafishIsoniazid (INH) is a first-line antituberculosis drug. The incidence of adverse reactions accompanied by inflammation in the liver during drug administration to tuberculosis patients is high and severely affects clinical treatment.
Editor's Pick Experimental TherapeuticsEfficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse ModelAN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis. In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid.
Mechanisms of Action: Physiological EffectsIsoniazid Bactericidal Activity Involves Electron Transport Chain PerturbationAccumulating evidence suggests that the bactericidal activity of some antibiotics may not be directly initiated by target inhibition. The activity of isoniazid (INH), a key first-line bactericidal antituberculosis drug currently known to inhibit mycolic acid synthesis, becomes extremely poor under stress conditions, such as hypoxia and starvation.